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Volume 9, No. 5 September/October 2017

ORIG INAL RESE ARCH

Etanercept and Ustekinumab Dosing for Psoriasis and Psoriatic ArthritisFor patients with psoriasis and/or psoriatic arthritis, actual-to-expected dosing ratios and costs were lower for etanercept than for ustekinumab.

Bonafede, Tang, Wilson, Huang, Harrison, and Stolshek

ORIG INAL RESE ARCH

Variation in the Coverage of Disease-Modifying Multiple Sclerosis Drugs Among US PayersAn examination of payer coverage for multiple sclerosis drugs shows variation in how these drugs are covered and in the evidence that payers review to make these decisions.

Chambers, Anderson, Wilkinson, and Rane

CON T INUING EDUCAT ION

Managing Chemotherapy-Induced Nausea and Vomiting (CINV) to Improve Patient CareExplore standard and emerging treatment options to manage chemotherapy-induced nausea and vomiting.

Barbour and Medina

WEB E XCLUSIVEFull content only available at www.ajpb.com

Compliance and Cost of Biologic Therapies for Rheumatoid ArthritisMedication compliance is associated with lower overall and disease-related healthcare costs in patients with moderate to severe rheumatoid arthritis receiving biologic therapies.

Bonafede, Johnson, Tang, Harrison, and Stolshek

Translating Evidence-Based Research into Value-Based Decisions®

®

®The American Journal of

PHARMACY BENEFITS

FROM THE EDI TOR

The Path to “Economic Value” in Specialty-Patient CareSpecialty pharmacies and managed care organizations will need to work together to truly balance the scale between cost and improved patient outcomes.

Steiber

PEER E XCHANGE

Biosimilars May Change the Treatment Landscape for Inflammatory Diseases Clinician and patient understanding and access considerations represent the most significant hurdles inhibiting the uptake of biosimilars for inflammatory conditions.

Santye and Toich

NAT IONAL PHARMACEU T ICAL COUNCIL

Guiding Practices for Patient-Centered Value AssessmentPhysician-, payer-, and patient-based organizations are increasingly developing frameworks that measure the value of a treatment and define it in terms of specific target audiences.

Leonard

138 The American Journal of Pharmacy Benefits® | September/October 2017

The American Journal of

PHARMACYBENEFITS

®

®EDITORIAL BOARDE D I T O R - I N - C H I E F & E X E C U T I V E V I C E P R E S I D E N T

Dan Steiber, RPhHighland Village, Texas

Kimberly A. Bergstrom, PharmDChief Clinical Officer McKesson Corporation San Rafael, CA

J. Lyle Bootman, PhD, ScDDean, College of Pharmacy University of Arizona Tucson, AZ

William B. Bunn, III, MD, JD, MPHVice President of Health, Safety, Security, & ProductivityNavistar International Warrenville, IL

Mitchell P. DeKoven, MHSAPrincipal, Health Economics & Outcomes Research, Real-World Evidence Solutions IMS Health Fairfax, VA

Joseph Doyle, RPh, MBASenior Director, Managed Markets Medical Science DirectorsAlkermes East Hanover, NJ

Steven R. Erickson, MDAssociate Professor, Department of Clinical Pharmacy University of Michigan Ann Arbor, MI

Gail R. Gratz-Levenson, RPhPrincipal, National Clinical PracticeBuck ConsultantsWashington, DC

Laura Long, MD, MPHPrincipalTheLongView, P.C. Columbia, SC

Rose Maljanian, RN, MBAChairman & CEO HealthCAWS, Inc Farmington, CT

Darlene M. Mednick, PhD, RPh, MBAVice President, Pharmacy Services Gorman Health Group New York, NY

Thomas J. Morrow, MDChief Medical OfficerNext ITSpokane, WA

Kavita Nair, PhDDepartment of Clinical Pharmacy University of Colorado Denver, CO

Cyndy Nayer, MACEO Center of Health Value Innovation Naples, FL

Edmund J. Pezalla, MD, MPHConsultantEJ Pezalla Independent ConsultantWethersfield, CT

Richard G. Popiel, MD, MBAExecutive Vice President & Corporate Chief Medical Officer Cambia Health SolutionsPortland, OR

Helen Sherman, PharmDVice PresidentSolid Benefit GuidancePortland, OR

William H. Shrank, MDDivision of Pharmacoepidemiology Harvard Medical School Boston, MA

Julie Slezak, MSExecutive Vice President, Clinical Analytics & Client ServicesGNS HealthcareRolling Meadows, IL

Yvonne Southwell, RPhVice President, Clinical Affairs CVS/Caremark Northbrook, IL

Dong-Churl Suh, PhD, MBADepartment of Pharmacy Practice and Administration Rutgers University Piscataway, NJ

Michael L. Taylor, MDFormer Chief Medical Officer Truven Health Analytics Ann Arbor, MI

MISSIONTo provide pharmacy and formulary decision makers with the information they need to improve the efficiency and health outcomes in managing pharmaceutical care.

EDITORIAL OVERVIEWThe American Journal of Pharmacy Benefits® (AJPB®) publishes peer-reviewed research that examines the impact of formulary management strategies on the utilization, cost, and quality of pharmacy services. AJPB® presents case studies, research, and evidence-based tools to help decision makers develop clinical strategies to manage pharmacy benefits for large populations.

Areas of particular interest include utilization management strategies (ie, prior authorization, step therapy, generic substitution, etc), outcomes research on Medicare Part D, formulary development and implementation strategies, research on adherence and compliance, cost-sharing strategies (ie, co-pays, coinsurance, CDHPs, HDHPs, etc), cost utility analyses, economic burden of disease, and comparative effectiveness analysis of drug therapies.

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Opinions expressed by authors, contributors, and advertisers are their own and not necessarily those of Managed Care & Healthcare Communications, LLC, the editorial staff, or any member of the editorial advisory board. Managed Care & Healthcare Communications, LLC, is not responsible for accuracy of dosages given in articles printed herein. The appearance of advertisements in this journal is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality, or safety. Managed Care & Healthcare Communications, LLC, disclaims responsibility for any injury to persons or property resulting from any ideas or products referred to in the articles or advertisements.

The American Journal of Pharmacy Benefits® ISSN 1945-4481 (print), ISSN 2164-2494 (online), UPS 0015-973 is published six times a year by Managed Care & Healthcare Communications, LLC, 2 Clarke Drive, Suite 100, Cranbury, NJ 08512. Copyright © 2017 by Managed Care & Healthcare Communications, LLC. All rights reserved. As provided by US copyright law, no part of this publication may be reproduced, displayed, or transmitted in any form or by any means, electronic or mechanical, without the prior written permission of the publisher. For permission to photocopy or reuse material from this journal, please contact the Copyright Clearance Center, Inc, 222 Rosewood Drive, Danvers, MA 01923; Tel: (978) 750-8400; Web: www.copyright.com. Reprints of articles are available in minimum quantities of 250 copies. To order custom reprints, please contact Br ian Haug , The American Journal of Pharmacy Benefits®, [email protected] / (609-716-7777). Subscrip t ion rates: Individual: $72/year (US); single copies: $20 each. The American Journal of Pharmacy Benefits® is a registered trademark of Managed Care & Healthcare Communications, LLC. www.ajpb.com. • Printed on acid-free paper.

I n this special edition of The American Journal of Pharmacy Benefits®, we shine a spotlight on the grow-ing dominance of specialty pharmaceuticals across

the overall healthcare landscape. According to QuintilesIMS, more than half of the top

20 drugs sold in the United States last year were specialty pharmaceuticals. Furthermore, while specialty drugs comprised less than 2% of the total prescriptions filled in the United States, these drugs accounted for approximately one-third of total commercial prescription drug spending in 2015, according to America’s Health Insurance Plans.

Within the specialty space, cancer, multiple sclerosis (MS), and inflam-matory conditions represented more than 60% of the total cost for specialty drugs billed through the pharmacy benefit, according to the National Conference of State Legislatures. As healthcare continues to transition toward a value-based system, this issue illustrates the value that specialty pharmacy brings across multiple disease states treated with high-cost therapies. Machaon Bonafede, PhD, MPH, and coauthors analyze the use of biologic drugs for rheumatoid arthritis to show the value that education provides to patients, especially in maintaining adherence.

To shine a spotlight on the varying strategies in the treatment of MS, James D. Chambers, PhD, and his coauthors examine how payers create individual prescription drug coverage policies that lead to differences in coverage for MS drugs, which subsequently affects patient access. Their findings show how inconsistency in evidence requirements from payers creates challenges for manufacturers in designing programs that support their products.

Our editor-in-chief, Dan Steiber, RPh, discusses how value-based contracting is separating itself from a volume- or fee-for-service–based system. The importance of a value-based approach lies in establishing a system of reimbursement based on indicators of value, including patient outcomes, efficiency, and quality. As noted in the article, each disease state presents itself with potential measures based on factors that include quality, cure, outcomes, and adherence.

It is abundantly clear that value-based care is not a fleeting trend but instead will allow specialty pharmacy to separate from the pack to demonstrate the value of its support services.

Thank you for reading.


PHARMACYBENEFITS

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Mike Hennessy, Sr Chairman and CEO

Finally Getting Real: BiosimilarsDan Steiber, RPH

specialtypharmacytimes.com/link/2593

Lipid Management for Patients With DiabetesYvette C. Terrie, BSPharm, RPh

pharmacytimes.com/link/168

External Partners + Integrated Services = Added Value, Efficiency for Specialty Drug ManufacturersJoe DePinto


ADDITIONAL RESOURCES


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®The American Journal of

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F R O M T H E E D I T O R

The Path to “Economic Value” in Specialty-Patient CareDan Steiber, RPh 142Specialty pharmacies and managed care organizations will need to work together to truly balance the scale between cost and improved patient outcomes.

P E E R E X C H A N G E

Biosimilars May Change the Treatment Landscape for Inflammatory DiseasesLauren Santye and Laurie Toich, Assistant Editors 145Clinician and patient understanding and access considerations represent the most significant hurdles inhibiting the uptake of biosimilars for inflammatory conditions.

O R I G I N A L R E S E A R C H

Etanercept and Ustekinumab Dosing for Psoriasis and Psoriatic ArthritisMachaon Bonafede, PhD, MPH; Derek H. Tang, PhD, BSPharm; Kathleen Wilson, MPH; Alice Huang, MS; David J. Harrison, PhD; and Bradley S. Stolshek, PharmD 150For patients with psoriasis and/or psoriatic arthritis, actual-to-expected dosing ratios and costs were lower for etanercept than for ustekinumab.


Variation in the Coverage of Disease-Modifying Multiple Sclerosis Drugs Among US Payers James D. Chambers, PhD; Jordan E. Anderson, BA; Colby L. Wilkinson, BA; and Pallavi Rane, PhD 155An examination of payer coverage for multiple sclerosis drugs shows variation in how these drugs are covered and in the evidence that payers review to make these decisions.

N A T I O N A L P H A R M A C E U T I C A L C O U N C I L

Guiding Practices for Patient-Centered Value Assessment Dan Leonard, President, National Pharmaceutical Council 160Physician-, payer-, and patient-based organizations are increasingly developing frameworks that measure the value of a treatment and define it in terms of specific target audiences.

C O N T I N U I N G E D U C A T I O N

Managing Chemotherapy-Induced Nausea and Vomiting (CINV) to Improve Patient Care Sally Yowell Barbour, PharmD, BCOP, CPP, FHOPA, and Patrick Medina, PharmD 162Explore standard and emerging treatment options to manage chemotherapy-induced nausea and vomiting.

Volume 9, No. 5 September/October 2017

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Vol. 9, No. 5 | The American Journal of Pharmacy Benefits® 141www.ajpb.com

Web Exclusive Content ( w w w . a j p b . c o m )


Compliance and Cost of Biologic Therapies for Rheumatoid ArthritisMachaon Bonafede, PhD, MPH; Barbara H. Johnson, MBA; Derek H. Tang, PhD, BSPharm; David J. Harrison, PhD; and Bradley S. Stolshek, PharmD

Objectives: To examine the association between treatment compliance with biologics approved for rheumatoid arthri-tis (RA) and 1-year total and RA-specific nonbiologic healthcare costs.

Study Design: Retrospective analysis of MarketScan Commercial Database claims data from July 1, 2009, to December 31, 2013.

Methods: Non-elderly adults (aged 18-63 years) with RA initiating treatment (index date) with a first-line biologic, with continuous plan enrollment for 6 months preindex and 12 months post index, were eligible. Outcomes included compliance (using proportion of days covered [PDC]) and persistence. Associations between compliance and total and RA-specific nonbiologic costs were assessed.

Results: Data from 14,696 patients were analyzed. Mean PDC (SD) was 0.65 (0.31); 46.8% of patients were persistent on index biologic. Mean total healthcare costs were $44,387 for intravenous abatacept, $40,434 for sub-cutaneous abatacept, $33,422 for adalimumab, $36,599 for certolizumab pegol, $33,214 for etanercept, $34,381 for golimumab, and $40,188 for infliximab. Compared with poorly compliant patients (PDC <0.2), total nonbiologic incremental costs for more compliant patients with PDC 0.2 to <0.4, 0.4 to <0.6, 0.6 to <0.8, and ≥0.8, respec-tively, were lower at –$1678 (cost ratio [CR] = 0.91; 95% CI, 0.86-0.97; P = .0025), –$4158 (CR = 0.78; 95% CI, 0.74-0.83; P <.0001), –$5127 (CR = 0.73; 95% CI, 0.69-0.78; P <.0001), and –$7961 (CR = 0.58; 95% CI, 0.56-0.62; P <.0001). The respective RA-related incremental nonbiologic costs, compared to poorly compliant patients, were $186 (CR = 1.08; 95% CI, 1.02-1.15; P = .0067), –$168 (CR = 0.92; 95% CI, 0.87-0.98; P = .0126), –$225 (CR = 0.90; 95% CI, 0.85-0.95; P = .0002), and –$560 (CR = 0.75; 95% CI, 0.71-0.79; P <.0001).

Conclusions: Better compliance was associated with lower overall and RA-related nonbiologic costs.

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Visit the journal archives section of ajpb.com for past issues and web exclusive articles from The American Journal of Pharmacy Benefits®.

Additional Resources

Value-Based Care in Specialty Populations: High-Quality Clinical Management of Home Infusion Hemophilia Patients Reduces Costs, Maintains OutcomesKirstin Schmidt, RN; Kim Milenski, RPh


Paper Argues That Bridging Studies Are Redundant, UnnecessaryKelly Davio

centerforbiosimilars.com/link/11

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Specialty Products: New World OrderDrug approvals over the past decade have shifted from the treatment of common health issues—such as diabetes, hypertension, and lipid management—toward more rare disease states with smaller patient populations. A key driver of this shift has been the successful challenge, or expiration, of patents, which has facilitated the availability of quality generics to treat most common health issues.

Markets and managed care organizations have played a very strong role in shifting utilization from branded products to generics, where those alternatives are available to community pharmacies that are dispensing more than 90% of their prescriptions using multisource products. A manufacturer can spend hundreds of millions of dollars to launch a new product, only to find that the market may not support it—for example, the recent approvals of PCSK9 inhibitors.

Purposeful hurdles have been established by payers to ensure appropriate utilization after more tradi-tional therapies and measures have failed to reach the desired end points. Because of this shift, the research and development efforts of manufacturers have, by and large, focused on what the market refers to as specialty products.

In 2016, the FDA approved 22 new molecular entities, all of which clearly fit the definition of specialty products: they are distributed through limited access; require special handling, distribution, and/or administration; are included in the FDA-mandated Risk Evaluation Mitigation Strategy program; are high in cost; and have complicated regimens with critical and proactive adverse effect management.

As we move closer to the end of 2017, these trends continue to play out. President Donald Trump has made it very clear to the FDA that the previous administration overregulated the approval process, and the need for new specialized therapies is essential. As such, we

anticipate a significant expansion of specialty products that will require the oversight and a partnership between specialty pharmacy and managed care to truly balance the scale between cost and improved patient outcomes.

Pharmacy Economics 101The economics of pharmacy have always been tied to providing a commodity to a patient at a price dictated by the cost of the product established by the manufacturer. Because most products are dispensed in the retail setting, any professional services provided by the community pharmacy were integrated into the price paid, either by the payer or the patient with co-pays, or both. Community pharmacy has been working hard as of late to establish provider status for pharmacists to help separate the distribution and dispensing elements from the service elements. That is the hope.

The Path to “Economic Value” in Specialty-Patient CareDan Steiber, RPh

The convergence of higher-cost products, changes in our healthcare system under the Affordable Care Act, and better coordination of care have not necessarily resulted in specialty pharmacy services getting compensated for their value.

LETTER FROM THE EDITOR


The Path to “Economic Value” in Specialty-Patient Care

Clearly, over the past several decades, pharmacy education has evolved and pharmacists have received a predominance of clinical education to the point where they currently play a key role on the healthcare team, with a focus on product selection, optimization, and patient outcomes. This certainly has become true in the specialty pharmacy space. However, this evolution has not been followed by the economics.

The convergence of higher-cost products, changes in our healthcare system under the Affordable Care Act, and better coordination of care have not necessarily resulted in specialty pharmacy services getting compensated for their value. There are only so many dollars to go around, including the patient shouldering more of a cost burden. Specialty is making progress, however, but it will still take hard evidence to demonstrate the incremental value that is being provided by enhanced services in the business and profession.

Even with specialty pharmacy, the bulk of the bottom line is driven by reimbursement focused on the average wholesale price or wholesale acquisition price. There are exceptions, driven primarily by specialty pharmacies that have agreements with payers or pharmacies owned by payers and/or manufacturers. In exchange for providing focused professional services, supply chain management, and data, some specialty pharmacies can supplement their revenues. Most pharmacies that may dispense a specialty product do not have service or direct distribution agreements in place with manufacturers. Arm yourself with the information our authors have diligently provided you.

“Show Me the Money”There are a good number of tactics being implemented in the market place, including value-based contracting (VBC). VBC involves payment, or reimbursement, based on indicators of value, such as patient health outcomes, efficiency, and quality. This is distinct from volume- or fee-for-service–based contracting, which involves payment for every unit of service delivered, often without terms related to outcomes, quality, or cost performance. Specialty must, therefore, objectively demonstrate what incremental value it brings toward optimizing patient outcomes.

Each therapeutic class or disease state presents itself with potential measures. Those measures can be based on multiple factors, including quality, cure, outcomes, adherence, cost, and potentially so many more. Often, the measures can be subjective based on how the patient feels. Objective measures, however, are best when designing a VBC initiative. Specialty pharmacy can be the focal point of data convergence and in the case of specialty products,

interpretation and action taken in the care and management of pharmaceutical care with multiple payers.

AJPB®: Supplying Specialty With ToolsIn this month’s edition of The American Journal of Pharmacy Benefits® (AJPB®), our authors have included several studies, the results of which demonstrate the hard costs and value that specialty pharmacy brings to the market around many therapeutic categories. Machaon Bonafede, PhD, MPH, and his team have researched the compliance and cost of biologic therapies for rheumatoid arthritis (RA) and clearly demonstrated the economic value provided through patient and provider education. The value of these services has been quantified and is remarkable, especially considering the cost, not only of products that treat RA, but also in treating these patients in general. Adherence to therapy is a key cornerstone provided by specialty and a basis of demonstrable value.

The results of this study show that across all index medication cohorts, compliant patients had consistently lower all-cause nonbiologic healthcare costs compared with noncompliant patients. Medication cost represents a large component of healthcare cost among patients with RA. Intuitively, although increasing compliance would increase their medication costs, understanding whether there may be a reduction in other healthcare costs due to improved outcomes is important to the overall care of the patient. Showing that improved compliance with biologics for RA reduces other healthcare costs can help a health plan justify new programs to boost compliance and patient outcomes.

We invite our readers to closely review the methodologies used in studies, such as those contained in our current and past editions of AJPB®. They are resources that may be deployed in your efforts to demonstrate value across the spectrum of stakeholders. VBC will be more than a passing fad, as more products, more patients, previously untreatable diseases, and few dollars will demand that value be provided. The trends will continue around separating the cost of the product for specialty services to demonstrating the value of those services.

AJPB® Is Evolving and We Invite You to Participate: Call for PapersAs we continue to refine AJPB®, we would like to reach out to our readers and request your contribution to sharing your experiences in our publication, your publication. We will continue to provide you with peer-reviewed articles, but in addition, we are expanding our focus to include the application of strategies and tactics in the areas of product access, reimbursement, services involving specialty »


Steiber

products, specialty pharmacy, providers, and pharma. We are seeking a balanced approach to our publication and contributions from professionals from the payer and managed markets sector. Below are some suggested topics. If you are interested, please reach out to us:

w Payer perspective: new products, innovation, or market share?

w Formularies for specialty and the expansion of therapy choices

w Payer perspective: gain clarity on the current state and direction of the healthcare landscape

w Health plan dynamics and utilization management strategies

w VBC

w Coverage decision making in a value-based landscape

w Techniques in gaining reimbursement, a payer’s perspective

AJPB® is committed to providing you both peer-written and -reviewed articles focused on the “real world” of managed markets and specialty pharmacy practice. We invite you to enjoy this issue and pass it on! We welcome

your feedback on this topic and on any topics you would like us to cover in future editions of AJPB®. Please reach out to us at [email protected] or [email protected], and we also encourage you and your colleagues to subscribe to this unique journal by logging on to www.ajpb.com.

Dan Steiber, RPh, is executive vice president and editor-in-chief of

The American Journal of Pharmacy Benefits®. Professionally, he is an

industry-leading consultant and has been responsible for managed

markets, commercial operations, and supply chain strategy. Mr Steiber

has served in several senior positions in pharmacy, distribution, and

industry over the course of his 40-year career.

Mr Steiber is a licensed pharmacist in Texas, Washington, California,

and Pennsylvania. He is affiliated with several professional associations

and publications and is a frequent speaker on behalf of many professional

organizations. He graduated from Washington State University College of

Pharmacy and has participated in a variety of postgraduate programs

in law and business development/marketing at Harvard University

and Northwestern University. Mr Steiber currently resides in Highland

Village, Texas.


B iosimilars have significant potential to lower escalating drug spending in the United States, but their adoption into practice in this country has been sluggish; how-

ever, this trend may soon change. Merck recently announced the launch of Renflexis (infliximab-abda), the second biosimilar version of the blockbuster drug, Remicade (infliximab). The first Remicade biosimilar, Inflectra (infliximab-dyyb) from Pfizer, launched in late 2016.

During the recent Peer Exchange®, “Clinician and Managed Care Insights on Biosimilars for Inflammatory Diseases” hosted by The Center for Biosimilars™, an expert panel provided an overview of biosimilars, clinician and patient understanding of the biologics landscape, and access considerations with a focus on inflammatory conditions. The panel was led by moderator Peter L. Salgo, MD, who was joined by experts Allan Gibofsky, MD; Gary R. Lichtenstein, MD; Vibeke Strand, MD; and Cole Wilson, PharmD.

Although biologics account for less than 1% of all prescrip-tions dispensed in the United States, they represent one-fourth of all US prescription spending, according to Dr. Salgo. The high cost of drugs is an increasing concern, and biosimilars offer hope as a less costly alternative for patients treated with specialty medications. Despite this potential, the adoption of biosimilars has been slow, due in part to knowledge gaps regarding biosimilars among healthcare professionals, according to the panel.

“(Biosimilars) have the real potential for lowering costs to the system and possibly increasing resources for patients and increasing their access,” Dr. Gibofsky said. “I think we still need some of that evidence to accrue before we’re fully comfortable, but I do think that the ability to use these drugs more widely will be a significant advantage in the treatment of the chronic inflammatory diseases we’ve been talking about.”

Although different representative organizations have launched programs to increase awareness, such as the American College of Rheumatology’s new Biosimilars Awareness Education Program, education overall is still lacking. Dr. Gibofsky said the gap lies between the time that the FDA

Biosimilars May Change the Treatment Landscape for Inflammatory DiseasesLauren Santye and Laurie Toich, Assistant Editors

Peter L. Salgo, MDColumbia University College of Physicians and Surgeons; New York-Presbyterian HospitalNew York, New York

Gary R. Lichtenstein, MDHospital of the University of PennsylvaniaPhiladelphia, Pennsylvania

Vibeke Strand, MDStanford University School of MedicineStanford, California

Allan Gibofsky, MDWeill Medical College of Cornell UniversityNew York, New York

Cole Wilson, PharmDCarolinas Health Care SystemCharlotte, North Carolina

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Santye | Toich

takes regulatory action and when the drug finally becomes available––which can be at least 6 months, maybe longer. “The knowledge base is building out there, but there are still some misunderstandings that have to be corrected,” he said.

Biosimilars contain living organisms and are designed to be highly similar to the reference product, but not identical. They are manufactured based on knowledge of the primary structure of the reference product—ultimately reverse engineering them. The primary structure, which is the sequencing of amino acids, needs to be the same for a biosimilar and its bio-originator, Dr. Gibofsky said.

“There can be differences in the molecule between a biosimilar and a bio-originator [the reference molecule], but they can’t be clinically meaningful,” Dr. Gibofsky said. “They can’t affect the safety. They can’t affect the efficacy. They can’t affect the purity or the potency of the molecule that we’re dealing with.”

The repurposing of drugs is gaining attention in the research world, in which biologic drugs indicated for a specific disease are being used to treat other diseases. Within the framework of biosimilar development, the FDA has allowed interchangeability for specific areas initially approved for the originator product.

“I think one of the concerns is that the FDA has made it very clear that the label for a biosimilar is identical to the label for the reference product,” Dr. Strand said. “That’s going to make it very hard for people to try to figure out how to report pharmacovigilance.” For biosimilars, 28 states currently allow interchangeability. According to Dr. Wilson, the standard for generic products that have been on the market is not the same standard for biosimilars.

Biosimilars are designed with a goal to decrease drug

costs and ultimately increase patient access. This decrease in cost is associated with how well the manufacturer of the biosimilar can negotiate compared with the negotiation skills of the manufacturer of the reference product.

“You can anticipate that you’re not going to see the bio-originator manufacturer stand still while someone else comes in and tries to eat their lunch,” Dr. Gibofsky said. “So, I’m not surprised to hear that there may be systems in which the bio-originator is priced even lower than the biosimilar, which was promised to be the reduced price.”

It is difficult to determine which drug will be cheaper, and by how much, due to the role pharmacy benefit managers play in making the decisions and the discount portfolios, according to the panelists. With the portfolios, there may be discounts for uses of various products—and there is no way of knowing what those discounts are.

Dr. Gibofsky spoke about his personal comfort level of biosimilar use by dividing patients into 3 categories: new starts, stable, and sleeping baby. For new-start patients, it is difficult to argue against putting them on a biosimilar. For patients who are stable and achieved that state relatively easily, it would not be that difficult to switch them to a biosimilar. But challenges arise in patients who have struggled to get to the point of low disease activity and remission. This type of patient is referred to as a “sleeping baby” because you don’t want anything done to disturb them. It would be difficult to switch the patient, and they would have more difficulty accepting the switch to a biosimilar, according to Dr. Gibofsky.

Two European switch clinical trials funded by the Norwegian and Danish governments examined the effects of switching from a bio-originator drug to its biosimilar. The results showed noninferiority when comparing the 2 products, according to the panel. Although there is promise when switching products to formulary or considering the use of biosimilars, the question remains whether the European studies are translatable to the United States and how this will that affect formularies, Dr. Salgo noted.

As far as costs in the rheumatology space, biosimilars typically start off slightly less expensive, but their threat is causing a cost reduction across the market. The current challenges with insurance companies and bio-originators will largely be the same with biosimilars. Dr. Gibofsky believes the prior authorization requirements and hurdles will be the same for biosimilars. “We are going to see insurance companies selecting favorite agents based on factors unrelated to their clinical applicability,” he said.

For rheumatologists, prior authorizations are one of the biggest expenses in terms of time and money. Many brand biologics cost hundreds of thousands of dollars, even with

There can be differences in the molecule between a biosimilar and a bio-originator, but they can't be clinically meaningful. They can't affect the safety. They can't affect the efficacy. They can't affect the purity or the potency of the moleule that we're dealing with.


Biosimilars May Change the Treatment Landscape for Inflammatory Diseases

discounts, which causes financial toxicity that can be just as harmful as any adverse event, according to Dr. Wilson.

From the perspective of the federal government, opening access may be less expensive per patient, but the more patients who come in, the higher the total bill gets—in other words, an aggregate bill. To reduce the financial burden of biologics, manufacturers offer discount programs, such as co-pay assistance; however, these services have yet to be put in place for biosimilars. It is also important to consider that there is little assistance available for generic-type products, which means biosimilars could follow the same trend.

When deciding which drug to prescribe, healthcare providers typically review efficacy, safety, adherence, tolerability, and cost, in addition to individual patient characteristics, according to Dr. Gibofsky. The interesting thing about biosimilars is that although they cannot compete with the reference product in the way physicians traditionally review drugs, they can offer a lower cost for the same clinical outcomes.

While cost may be a major reason that physicians choose to prescribe a biosimilar, some may be concerned that switching patients from a reference product may not achieve the same disease control, despite data suggesting otherwise. Physicians may also be hesitant to prescribe biosimilars if the reduced price does not necessarily translate into patient savings. In some cases, a patient’s co-pay may be the same, with savings only being seen by the healthcare system, according to the panel.

Biosimilars typically offer a cost reduction ranging from 15% to 30% of the cost of the reference product compared with an approximately 85% reduction from standard generic drugs. As such, the cost concessions from biosimilars may not be enough to change the prescribing habits of physicians, according to the panel. Dr. Strand said that contracting will play a significant role in how much biosimilars will be discounted.

The manufacturing and approval processes are costly for biologic drugs, which may be another reason why the initial discounts for biosimilars are not more remarkable. The panel also noted that the reference product has already generated revenue, causing manufacturers to have the financial ability to provide larger discounts. Therefore, it may not be a question of why biosimilars are less costly, but why reference products are not discounted more, according to the panel.

In Europe, a majority of biosimilars offer a 30% discount, which is at the higher end of what is expected in the United States. Dr. Gibofsky said that these countries are largely single-payer systems, which opens the door to price negotiations due to the expansive size of the contracts, as

opposed to the healthcare system United States. Addition-ally, since biosimilars were introduced in Europe so long ago, physicians tend to be more comfortable prescribing the drugs, which may lead to higher manufacturer discounts.

Ensuring that a biosimilar is covered by payers is crucial because it likely will not be prescribed without reimbursement. Taking cost out of the conversation, payers must consider numerous factors, including clinical efficacy, appropriateness, and comparisons to the reference product. While the goal is to secure access for patients, limited networks may provide a challenge for continual care. For example, Dr. Wilson said that patients may have access to the drug through an acute setting, but could lose coverage when transitioned to an outpatient setting. These are considerations payers must account for to ensure that they are being fiscally responsible and are lowering healthcare costs.

This issue may be further complicated by state-by-state approvals of biosimilars. Even if the FDA approves a biosimilar as interchangeable, many states have passed legislation that dictates whether the reference product can be substituted for the biosimilar without involvement from the prescriber. However, Dr. Lichtenstein believes that it might be more appropriate for the federal government to make a country-wide regulation regarding interchange-ability. In some cases, state legislators may not have all of the necessary information to make the decisions, whereas federal legislators have access to nonpublic information and clinical trials.

Both physicians and patients are entering a new world with the introduction of biosimilars. For newly diagnosed patients, physicians can embark on the standard discussion about treatment and initially prescribe a biosimilar, but switching patients off a reference product may be more challenging. Patients who are not responding well to a biologic drug, however, may be more willing to switch

Prescribers are tasked with educating patients and reassuring them that they will receive the same results on a biosimilar as they did on a biologic.


Santye | Toich

to a biosimilar. Patients may also be less likely to switch treatments if they have the same co-pay.

Prescribers also are tasked with educating patients and reassuring them that they will achieve the same results on a biosimilar as they did on a biologic. The experts suggest that if patients are concerned over the small changes in biosimilars, prescribers should ensure them that the drugs have been tested in different disease states and data suggest the change will not be harmful. Dr. Strand noted that more high-level details about biosimilars are known compared with the reference product. The panel emphasized that physicians need education regarding biosimilars to become more comfortable with prescribing the drugs, which may result in larger uptake.

Since there are more than 50 biosimilars under review by the FDA, it is clear this new class of drugs is here to stay, according to the panel. This requires physicians to plan their course of action when talking to patients

about treatment. Manufacturers have to do a great deal of planning, from creation of the biosimilar to its approval. They also must conduct extensive studies to determine how switching treatments will affect patients. Although the biosimilar industry is developing slowly, the experts agreed that the drugs will likely change the way diseases are managed for numerous conditions.

Dr. Wilson concluded that when generic drugs emerged, conversations took place that were similar to the current issues surrounding biosimilars, which he said may turn out to be as important to the industry as generics.

“The opportunities with biosimilars are great. They’re great for patient choice, they’re great for provider choice, and they can have a lot of cost savings and opportunities,” Dr. Wilson said. “I think the future will tell a lot of the litigations and the limitations. The access channels of some of these (that first come to market) will really pave the way for the future of biosimilars and how we use them in our practice.”


ABSTRACT

Objectives: To compare estimated actual dosing of etanercept and ustekinumab in patients with psoriasis and/or psoriatic arthritis with recommended dosing, and to estimate annual cost of these psoriasis treatments.

Study Design: Retrospective, observational cohort study.

Methods: Administrative claims data from a commercial claims database from January 1, 2010, through December 31, 2013, were analyzed. Patients had a diagnosis of psoriasis and/or psoriatic arthritis, and continuous enrollment with medical and pharmacy benefits for the 12-month preindex period and the 12-month post index follow-up period. Dosing was determined with actual-to-expected dose ratios computed while patients were persistent to therapy. Expected dose was calculated ac-cording to US Package Inserts; expected weight-based dosing of ustekinumab was estimated using random weight assign-ment based on starting dose. Annual psoriasis-related costs consisting of biologics, nonbiologic psoriasis therapies, and psoriasis-related healthcare utilization were calculated.

Results: Data from 2997 patients (2128 etanercept, 869 ustekinumab) were analyzed. Actual-to-expected dose ratios (SD) for etanercept and ustekinumab were 0.939 (0.304) and 1.169 (0.687), respectively, for all patients; 1.012 (0.295) and 1.164 (0.666) for patients with psoriasis but without psoriatic arthritis; and 0.783 (0.261) and 1.203 (0.813) for patients with psoriatic arthritis. Annual costs (SD) for all patients were $28,291 ($13,296) and $37,537 ($17,209) for etanercept and ustekinumab, respectively; for psoriasis pa-tients without psoriatic arthritis, they were $29,712 ($13,988) and $36,976 ($16,817), respectively; and for patients with psoriatic arthritis, they were $25,246 ($11,084) and $41,068 ($19,199), respectively.

Conclusions: Actual-to-expected dosing ratios and annual costs were lower for etanercept than for ustekinumab in pa-tients with psoriasis and/or psoriatic arthritis.

Am J Pharm Benefits. 2017;9(5):150-154

A ctual use of medications is important for payers to predict the cost of a treatment. Low variation between actual versus expected dosing can reduce the

uncertainty of drug expenses, which can be beneficial from the payer’s budgeting perspective. There is a lack of evidence on actual dosing versus expected dosing patterns and costs of biologic therapies used for psoriasis and/or psoriatic arthritis. Drugs that possess the combined characteristics of low expected cost and minimal uncertainty of such cost would be optimal to payers.

Etanercept (a tumor necrosis factor inhibitor) and ustekinumab (an interleukin [IL]-12 and IL-23 blocker) are commonly used biologic therapies for the treatment of moderate to severe plaque psoriasis, with both drugs being efficacious in treating psoriatic arthritis. Etanercept for psoriasis is administered subcutaneously (SC) at a starting dose of 100 mg/week for 12 weeks followed by a maintenance dose of 50 mg/week.1 Ustekinumab is administered SC based on weight: 45 mg for patients weighing ≤100 kg (220 lbs) and 90 mg for patients >100 kg, with the first 2 doses 4 weeks apart followed by a dose every 12 weeks.2 These biologics are expected to be generally representative of biologics used to treat plaque psoriasis that use standard dosing and weight-based dosing.

A study by Thayer et al that examined actual versus expected dosing with etanercept showed that patients with psoriasis and/or psoriatic arthritis used 89% to 107% of the expected dose based on claims data from 2003 to 2008.3 This wide range was dependent on whether dosing was based on the psoriasis or psoriatic arthritis indication. Actual versus expected dosing patterns and costs for ustekinumab or other biologics used to treat moderate to severe plaque psoriasis have not been reported to date. The objective of this study was to estimate current actual dosing of etanercept and ustekinumab in patients with psoriasis and/or psoriatic arthritis and compare it with the recommended dosing in the US Package Inserts (USPIs), and to estimate annual psoriasis-related costs.

Etanercept and Ustekinumab Dosing for Plaque Psoriasis and Psoriatic ArthritisMachaon Bonafede, PhD, MPH; Derek H. Tang, PhD, BSPharm; Kathleen Wilson, MPH; Alice Huang, MS; David J. Harrison, PhD; and Bradley S. Stolshek, PharmD

ORIGINAL RESEARCH


Etanercept and Ustekinumab Dosing for Psoriasis and Psoriatic Arthritis

METHODSData SourceData for this analysis were obtained from the Truven Health MarketScan Commercial Claims and Encounters Database. This database contains the annual inpatient, outpatient, and out-patient prescription drug experience of 30 million commercially insured US patients. Enrollees are covered under a variety of fee-for-service and managed care health plans, including exclusive provider organizations, preferred provider organizations, point-of-service health insurance plans, indemnity plans, and health maintenance organizations.

Study DesignThis was a retrospective, observational cohort study based on US administrative claims data from the Truven Health MarketScan® Commercial Database. Data were collected from January 1, 2010, through December 31, 2013 (FIGURE 1). The first new claim for etanercept or ustekinumab (index agent) between January 1, 2011, and December 31, 2012, was the index event/date. The baseline period comprised the 12 months prior to the index date, and the follow-up period was the 12 months after the index date. Patients were new to any biologic and had no outpatient medical claim or prescription claim for any biologic approved prior to initiation of the index agent.

Patient IdentificationInclusion criteria were: an outpatient medical or prescription claim for etanercept or ustekinumab between January 1, 2011, and December 31, 2012; continuous enrollment with medical and pharmacy benefits for the 12-month baseline period and the 12-month follow-up period; aged 18 to 63 years on index date; and a diagnosis of psoriasis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 696.1x) and/or a diagnosis of psoriatic arthritis (ICD-9-CM code 696.0x) during the baseline period. Exclusion criteria included a diagnosis for any other indication for etanercept, including rheumatoid arthritis (ICD-9-CM code 714.0x), juvenile idiopathic arthritis (ICD-9-CM code 714.3x), or ankylosing spondylitis (ICD-9-CM code 720.0x); evidence of index biologic medication use during the baseline period; evidence of ≥2 claims for a different biologic on the index date; or evidence of receiving an outlier dose during the follow-up period. Outlier doses for etanercept were <12.25 mg (half the minimum label dose) or >200 mg (double the maximum label dose) per week, and for ustekinumab were <11.25 mg or >180 mg per claim.

Study OutcomesOutcomes included the estimate of the ratio of actual dosing to expected dosing as defined by the USPI while persistent on index medication (no gap ≥45 days and no switching) during the follow-up period. For patients on ustekinumab, patient weight was inferred because weight data are not included in the database. Individual patient weight was assigned based on starting dose such that patients who initiated ustekinumab with an initial dose >67.5 mg were assumed to be high-weight patients (>100 kg) who required a dose of 90 mg; the remaining patients who initiated at a dose ≤67.5 mg were considered low-weight (≤100 kg), requiring a dose of 45 mg (weight based on starting dose). A preliminary query of the data indicated that 47.4% of patients initiated a dose closer to 90 mg per claim, while 52.6% of patients initiated with a dose closer to 45 mg per claim. As a sensitivity analysis, weight distributions from similar age and gender groups were derived from clinical trial data,4 where ~69% of psoriasis patients weighed ≤100 kg and 31% weighed >100 kg. Patient weight was assigned as a dichotomous variable so that the distribution of the study sample matched the weight distribution reported by Lebwohl et al (midpoint weight assignment).4 These weight distributions were used to inform the expected dose for ustekinumab in this study population, and results for patients on ustekinumab represent the average for the entire cohort.

PRACTICAL IMPLICATIONSDosing and usage of medications are important for payers to estimate the cost of treatment. In this analysis of data from a commercial claims database, the actual-to-expected dosing ratio was lower for etanercept than for ustekinumab. Additionally, annual costs consisting of biologics, non-biologic psoriasis therapies, and psoriasis-related healthcare utilization were lower for etanercept than for ustekinumab. Payers may consider these findings when predicting the cost of treatment for patients with moderate to severe plaque psoriasis receiving etanercept or ustekinumab.

Figure 1. Study Periods

Follow-up period: 12 months continuous enrollment after index date

Patient selection period: identification of index date

Baseline period: 12 months continuous enrollment before index date

1/1/20111/1/2010 12/31/2012 12/31/2013


Bonafede et al

Annual treatment costs during the follow-up period were calculated. Costs included index biologic costs, total biologic therapy costs (for patients who switched biologics), and total psoriasis-related costs. Psoriasis-related costs included the cost of inpatient, outpatient, emergency department claims with a diagnosis of psoriasis in the primary diagnosis position, and costs of all nonbiologic and biologic agents approved for psoriasis treatment, including topical prescription therapy, phototherapy, and oral or intravenous corticosteroids. Healthcare costs were adjusted to 2013 US dollars using the Medical Care component of the Consumer Price Index.

Statistical ConsiderationsThis study was descriptive only, and no formal hypothesis was tested. Actual dosing data were calculated during the time period when patients were persistent (no gap ≥45 days and no switching). Descriptive results were stratified by diagnosis (all psoriasis patients with or without psoriatic arthritis, psoriasis patients without psoriatic arthritis, and patients with psoriatic arthritis). Chi-square and t tests were used to compare categorical and continuous variables, respectively, between etanercept and ustekinumab.

RESULTSPatientsA total of 2997 eligible patients (2128 etanercept, 869 ustekinumab) were identified in the database. The mean age was 45 years, and slightly more than half of patients were male (TABLE 1). Patients on etanercept and those on ustekinumab had similar baseline Deyo Charlson Comorbidity Index scores. More patients on etanercept had psoriatic arthritis (n = 677; 31.8%) compared with patients on ustekinumab (n = 119; 13.7%).

Actual-to-Expected DosingFor psoriasis patients with or without psoriatic arthritis, the actual mean (SD) dose for etanercept was 2176 (1255) mg and was 195 (130) mg for ustekinumab during the 12-month follow-up. Ratios of actual doses to expected doses were slightly higher for patients on ustekinumab based on random weight assignment than for patients on etanercept (FIGURE 2). In the sensitivity analysis, ratios were lower for ustekinumab based on midpoint weight assignment compared with weight based on starting dose.

CostsTotal psoriasis-related costs were lower for etanercept than for ustekinumab during the 12-month follow-up period (P <.001), including index biologic costs (P <.001) and other psoriasis- or psoriatic arthritis–related costs (P = .034) (TABLE 2). Annual costs (SD) for all patients were $28,291 ($13,296) and $37,537 ($17,209) for etanercept and ustekinumab, respectively; for psoriasis patients without psoriatic arthritis, they were $29,712 ($13,988) and $36,976 ($16,817); and for patients with psoriatic arthritis, they were $25,246 ($11,084) and $41,068 ($19,199). Across all patients, the annual cost for biologic therapy (SD) was $26,784 ($13,072) for etanercept and $35,686 ($16,897) for ustekinumab.

DISCUSSIONIn this study of real-world etanercept and ustekinumab dosing patterns for moderate to severe plaque psoriasis

Table 1. Demographic and Clinical Characteristics at Index Date

CharacteristicEtanercept (N = 2128)

Ustekinumab (N = 869)

Age, years: mean (SD) 45.2 (11.6) 45.2 (11.2)

Male: n (%) 1076 (50.6) 486 (55.9)

Geographic region: n (%)

Northeast 368 (17.3) 163 (18.8)

North Central 472 (22.2) 193 (22.2)

South 868 (40.8) 352 (40.5)

West 386 (18.1) 155 (17.8)

Unknown/missing 34 (1.6) 6 (0.7)

Insurance plan type: n (%)

Fee-for-service 47 (2.2) 17 (2.0)

Health maintenance organization 383 (18.0) 140 (16.1)

Point-of-service 214 (10.1) 77 (8.9)

Preferred provider organization 1224 (57.5) 523 (60.2)

Othera 260 (12.2) 112 (12.9)

PsA: n (%) 677 (31.8) 119 (13.7)

Deyo Charlson Comorbidity Index: mean score (SD)

0.3 (0.8) 0.3 (0.9)

Comorbid conditions: n (%)

Anxiety 181 (8.5) 72 (8.3)

Asthma/COPD 171 (8.0) 62 (7.1)

CVD (excluding hypertension) 156 (7.3) 67 (7.7)

Depression 226 (10.6) 82 (9.4)

Diabetes 236 (11.1) 99 (11.4)

Hypertension 530 (24.9) 200 (23.0)

Osteoarthritis 258 (12.1) 66 (7.6)

Concomitant medications: n (%)

Nonbiologic systemic therapy 597 (28.1) 174 (20.0)

Topical medication 1638 (77.0) 644 (74.1)

Phototherapy 147 (6.9) 65 (7.5)

Corticosteroids 921 (43.3) 308 (35.4)

aOther insurance plan types included consumer-driven health plans, high-deductible health plans, and unknown or missing plans.CVD indicates cardiovascular disease; COPD, chronic obstructive pulmonary disorder.


Etanercept and Ustekinumab Dosing for Psoriasis and Psoriatic Arthritis

and/or psoriatic arthritis, we found higher than expected rates of high-dose ustekinumab use. In contrast, actual doses of etanercept were lower than expected across all patients and for those patients with psoriatic arthritis, and were slightly above expected doses among patients with psoriasis only. Managers of healthcare plans that attempt to predict costs of ustekinumab should consider these findings and should not make assumptions on weight-based dosing based on patient populations enrolled in clinical trials.

Trends observed in this study are consistent with an analysis of adminis-trative claims data by Thayer et al3 that evaluated etanercept treatment patterns in psoriasis patients with and without psoriatic arthritis. In the Thayer study, patients with only psoriasis received 107% of the expected dose (compared with 100% in our analysis), and patients with psoriatic arthritis received 89% of the expected dose (compared with 78% in our analysis).

A possible reason for the differences in etanercept and ustekinumab actual-to-expected dosing ratios observed in our study may be due to dose escalations and reductions. An analysis based on administrative claims data showed that patients on etanercept had a higher rate of dose escalation at 12 months of treatment (41.0%) compared with those on ustekinumab (35.9%), but the etanercept cohort also had higher rates of dose reductions (48.7%) compared with the ustekinumab cohort (37.4%).5 A cross-sectional study of a clinical practice in Spain reported dose escalation in 17.9% and 4.2% of patients on ustekinumab and etanercept,

respectively, and dose reductions in 46.4% and 41.6%.6 The overall annual mean reduction in dose per patient was 0.9% for ustekinumab and 13.8% for etanercept.6 In a phase 3 trial of ustekinumab, 51% of patients had an increase in dose based on an efficacy algorithm.7 In a randomized controlled trial of etanercept, dose reductions were not associated with a decrease in efficacy.8

LimitationsLimitations of the study were inherent to the use of claims data for retrospective analyses. The results are limited to individuals with commercial health coverage and may not be generalizable to uninsured or underinsured patients, or those on Medicare. Claims could be misclassified and

The ratio of actual dose based on claims data to expected dose based on the US Product Inserts is shown for patients on etanercept (purple bars), patients on ustekinumab with expected dose based on random weight assignment (light green bars), and patients on ustekinumab with expected dose based on midpoint weight assignment (dark green bars bars) is shown. Ratios that are >1 represent higher dose or more frequent dosing than expected, and ratios <1 represent lower dose or less frequent dosing than expected. Error bars represent SD.

PsA indicates psoriatic arthritis; PsO, psoriasis.

Figure 2. Ratios of Actual Dose to Expected Dose

Table 2. Estimated Annual Cost per Patient

Cost, US$: mean (SD)

All Patients PsO Only PsA

Etanercept (N = 2128)

Ustekinumab (N = 869)

Etanercept (n = 1451)

Ustekinumab (n = 750)

Etanercept (n = 677)

Ustekinumab (n = 119)

Annual medical costa 28,291 (13,296)** 37,537 (17,209) 29,712 (13,988)** 36,976 (16,817) 25,246 (11,084)** 41,068 (19,199)

Biologic therapy cost 26,784 (13,072)** 35,686 (16,897) 28,459 (13,699)** 35,516 (16,671) 23,194 (10,780)** 36,756 (18,297)

PsO/PsA-related costb 1507 (3246)* 1850 (5454) 1253 (2433) 1460 (3488) 2052 (4474)** 4312 (11,599)

aHealthcare costs were summed over the 12-month follow-up period. Healthcare costs are expressed in 2013 constant dollars, adjusted using the Medical Care component of the Consumer Price Index. Costs were measured using the financial fields on administrative claims in the MarketScan Databases and include the gross covered payments for all healthcare services or products, ie, the amount eligible for payment after applying pricing guidelines such as fee schedules and discounts, but including deductibles, co-payments, and coordination of benefits.bAnnual psoriasis- or psoriatic arthritis-related costs included the inpatient, outpatient, and emergency department claims with a diagnosis of psoriasis or psoriatic arthritis in the primary position. Medication costs included the cost of nonbiologic systemic agents (methotrexate, sulfasalazine, and cyclosporine), topical prescription therapy, phototherapy, and corticosteroids (oral and intravenous).PsA indicates psoriatic arthritis; PsO, psoriasis. *P <.05.**P <.01.

All Patients PsO Only PsA

0.94N = 2128

1.17N = 869

0.91N = 869

1.01N = 1451

1.16n = 750

0.91n = 750 0.78

n = 667

1.20n = 119

0.91n = 119

0

0.5

1

1.5

2

2.5

Actu

al D

ose:

Expe

cted

Dos

e (+

SD)

Ustekinumab (weight based on starting dose)Etanercept

Ustekinumab (midpoint weight assignment)


Bonafede et al

could be subject to data coding and entry errors. Cost data were associated with outpatient medical procedures, and line items could not be identified separately, which may have affected cost estimations. Administrative claims data do not contain information on disease severity or effects of treatment. It is not possible to determine whether patients had only psoriatic arthritis, which may warrant a different dosing regimen. Also, dose and weight distributions were not comparable with the results from the study used to estimate weight distributions.4 In this analysis, a higher proportion of patients (~50%) initiated at 90 mg, resulting in higher than expected doses using the random weight assignment for ustekinumab. It is possible that some patients received ustekinumab at an incorrect weight-based dose (eg, a 45-mg dose for a patient who weighed more than 100 kg).

CONCLUSIONSPatients initiating psoriasis and/or psoriatic arthritis treatment with etanercept had a 20% lower actual-versus-expected dosing ratio while persistent on therapy and 25% lower total annual psoriasis-related costs than did patients initiating ustekinumab. These results suggest that products with variable dosing, such as ustekinumab, can introduce cost-related uncertainties for payers.

ACKNOWLEDGMENTSDikran Toroser (Amgen Inc) and Julia R. Gage (on behalf of Amgen Inc) provided medical writing support.

Author Affiliations: Truven Health Analytics (MB, KW, AH), Cambridge, MA; Amgen Inc (DHT, DJH, BSS), Thousand Oaks, CA.

Source of Funding: This study was sponsored by Immunex, a wholly owned subsidiary of Amgen Inc, and by Wyeth, which was acquired by Pfizer in October 2009.

Author Disclosures: Dr Bonafede, Ms Wilson, and Ms Huang are employees of Truven Health Analytics, which received funding from Amgen Inc, for this study. Dr Tang is a former employee and current shareholder of Amgen Inc.

Drs Harrison and Stolshek are employees and shareholders of Amgen Inc.

Authorship Information: Concept and design (MB, DHT, KW, AH, DJH); acquisition of data (MB, KW, AH); analysis and interpretation of data (MB, DHT, KW, AH, DJH, BSS); drafting of the manuscript (MB); critical revision of the manuscript for important intellectual content (MB, DHT, KW, AH, DJH, BSS); statistical analysis (MB, KW, AH); provision of patients or study materials (MB); administrative, technical, or logistic support (DHT, KW, AH); and supervision (DHT, BSS).

Address Correspondence to: Machaon Bonafede, PhD, MPH, Truven Health Analytics, 150 Cambridge Park Dr, Cambridge, MA 02140. E-mail: [email protected].

REFERENCES1. Enbrel (etanercept) [prescribing information]. Thousand Oaks, CA: Immunex Corp; 2015.2. Stelara (ustekinumab) [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2012.3. Thayer S, Watson C, Song R, Globe DR, Harrison DJ. Etanercept treatment patterns in managed-care patients with psoriasis or psoriatic arthritis. J Med Econ. 2010;13(2):228-235. doi: 10.3111/13696998.2010.487469.4. Lebwohl M, Yeilding N, Szapary P, et al. Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations. J Am Acad Dermatol. 2010;63(4):571-579. doi: 10.1016/j.jaad.2009.11.012.5. Feldman SR, Zhao Y, Navaratnam P, Friedman HS, Lu J, Tran MH. Patterns of medication utilization and costs associated with the use of etanercept, adalim-umab, and ustekinumab in the management of moderate-to-severe psoriasis. J Manag Care Spec Pharm. 2015;21(3):201-209.6. Baniandrés O, Rodríguez-Soria VJ, Romero-Jiménez RM, Suárez R. Dose modification in biologic therapy for moderate to severe psoriasis: a descriptive analysis in a clinical practice setting. Actas Dermosifiliogr. 2015;106(7):569-577. doi: 10.1016/j.ad.2015.02.003.7. Langley RG, Lebwohl M, Krueger GG, et al; PHOENIX 2 Investigators. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol. 2015;172(5):1371-1383. doi: 10.1111/bjd.13469. 8. Papp KA, Tyring S, Lahfa M, et al; Etanercept Psoriasis Study Group. A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction. Br J Dermatol. 2005;152(6):1304-1312.


ABSTRACT

Background: In US healthcare, individual payers create their own prescription drug coverage policies. This can lead to differ-ences in how payers cover multiple sclerosis (MS) drugs and can thus affect patients’ access to them.

Objectives: To examine how the largest private payers cover MS drugs relative to their corresponding FDA approvals and to the evidence that payers report reviewing when formulating their policies.

Methods: We identified coverage policies for disease-modifying MS drugs issued by the 10 largest private payers that make their policies publicly accessible. We categorized each policy relative to the drug’s corresponding FDA approval as consistent, more restrictive, less restrictive, or “mixed,” ie, more restrictive than the approval in 1 way, but less restrictive in another. We then categorized the evidence that the payers reported review-ing in their policies into 6 categories: randomized controlled tri-als (RCTs); other clinical studies (eg, non-RCTs or observational studies); clinical reviews; health technology assessments; clinical guidelines; or cost-effectiveness analyses.

Results: Forty-six percent of coverage policies were more restrictive than the corresponding FDA approval, 38% consis-tent, 12% less restrictive, and 3% mixed. The payers reported reviewing an average of 1.1 RCTs, 0.4 technology assess-ments, 0.4 other clinical studies, 1.3 clinical reviews, and 0.8 clinical guidelines per policy. Only 1 payer reported reviewing cost-effectiveness analyses. Payers reported reviewing varying numbers of studies and reviewing differing study types in their coverage policies.

Conclusions: We found variation in how the included payers cover MS drugs and in the evidence that they report reviewing in their coverage policies.

Am J Pharm Benefits. 2017;9(5):155-159

C ompared with healthcare systems in other developed countries, the healthcare system in the United States is notably fragmented, with multiple decision makers at

the national and local levels.1-3 This fragmentation is apparent in the insurance market, which consists of multiple public payers (including Medicaid, Medicare, the Children’s Health Insurance Program, and the Veterans Health Administration) and private payers. As a consequence, multiple sclerosis (MS) patients across the United States receive their prescription drug insurance coverage from a variety of healthcare payers. Because payers develop their own coverage criteria to guide how their enrolled beneficiaries use drugs and biologics, different patients receiving drug coverage from different payers may have differing access to MS drugs.

We have examined how US payers cover medical technologies in a number of studies. In 1 study, we found variation in how payers cover a variety of interventions, including medications, medical devices, surgeries, and diagnostic imaging and tests.4 In another study, we found variation in how private payers cover rheumatoid arthritis treatments and in the evidence that they reported reviewing in their coverage policies.5 In a separate study, we found inconsistencies in how the largest private payers and Medicare cover medical devices.6 Other researchers have also found variation in how payers cover medical technologies, notably in regard to personalized medicine technologies.7,8

The current study builds on this body of research by examining how the largest US-based private payers cover MS drugs. Our study had 2 objectives. First, we compared how the largest private payers covered disease-modifying drugs relative to their FDA approval. Second, we examined the evidence base that the payers reported reviewing when formulating their coverage policy.

METHODSWe identified the largest US private payers in terms of market share as reported by the National Association of Insurance Commissioners.9 We then searched each payer’s website to determine whether the payer made its coverage policies publicly

Variation in the Coverage of Disease-Modifying Multiple Sclerosis Drugs Among US PayersJames D. Chambers, PhD; Jordan E. Anderson, BA; Colby L. Wilkinson, BA; and Pallavi Rane, PhD

ORIGINAL RESEARCH


Chambers et al

accessible. We included the 10 largest payers that make their coverage policies publicly accessible. We excluded Kaiser Permanente and the WellCare Group because they do not publish the required coverage information. We included the following payers in this study (ranked in order of size): UnitedHealthcare, Anthem, Humana, Health Care Service Corporation (HCSC), Aetna, Highmark, Centene, Independence Health Group, Blue Cross Blue Shield of Florida, and Blue Cross Blue Shield of Michigan.

We then searched each included payer’s coverage policies for those pertaining to disease-modifying MS drugs. When a payer had a number of health plan offerings, we included the coverage policies relevant to their commercial line of business. Coverage policies were current as of April 1, 2016. We included coverage policies pertaining to the following disease-modifying MS drugs: dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta-1a (available as 2 branded products, Avonex and Rebif), interferon beta-1b (available as 2 branded products, Betaseron and Extavia), peg-interferon beta-1a, natalizumab, teriflunomide, mitoxantrone, and alemtuzumab. To be consistent with the included payers’ coverage policies, when a drug was associated with 2 different brand names, we considered each brand separately in the analysis.

Coverage Relative to the Drug’s FDA ApprovalWe obtained each drug’s FDA label from the FDA website.10 The included FDA labels were current as of April 1, 2016. The drugs in the sample were indicated for patients with relapsing forms of MS (RRMS). Interferon beta-1a (Avonex) and interferon beta-1b (Betaseron and Extavia) were additionally indicated for patients who had experienced a first clinical episode and had magnetic resonance imaging (MRI) features consistent with MS.

We compared each coverage policy with the drug’s corresponding FDA approval, accounting for the labeled indication, contraindications, and black box safety warnings. We used an approach similar to what we used to examine coverage policies for rheumatoid arthritis drugs in a previous study.5 First, we determined whether a drug was covered

by the payer. We then categorized payer coverage for MS drugs as more restrictive than the FDA approval (the payer placed conditions on coverage beyond the FDA approval); consistent with the FDA approval; less restrictive than the FDA approval (the payer provided coverage for off-label usage not included in the FDA label); or mixed (the payer’s coverage policy was more

restrictive than the FDA label in 1 way, but was less restrictive in another). An example of a mixed coverage policy was Centene’s policy for interferon beta-1a (Rebif). Centene covered interferon beta-1a (Rebif) for patients with clinically isolated syndrome (an initial episode of neurologic symptoms of duration of at least 24 hours caused by demyelination or inflammation) with MRI features consistent with MS, which was an off-label usage, but covered the drug only for patients who had first failed 2 or more alternative drugs, a condition not included in the FDA label.

For coverage policies that we found to be more restrictive than the corresponding FDA approvals, we categorized the restrictions on coverage as step-therapy restrictions (the payer restricted coverage to patients who had first failed an alternative treatment) or patient restrictions (the payer restricted coverage to patients suffering from disease of a particular type or severity).

Evidence Base the Payers Reported ReviewingWe reviewed each coverage policy to identify the evidence that the payers cited or discussed reviewing within it. We categorized the evidence into the following 6 categories: randomized controlled trials (RCTs), other clinical studies (eg, nonrandomized controlled trials, prospective cohort studies, and consecutive case series studies), clinical reviews (including systematic reviews of clinical evidence), clinical guidelines, health technology assessments, and cost-effective analyses. We did not account for studies that did not pertain to the drug of interest, eg, epidemiological studies, or studies that were not published in the peer-reviewed literature or promulgated by major clinical societies or health technology assessment agencies. We reported the frequency that the payers reviewed evidence in each category.

RESULTSWe identified 93 coverage policies for 12 disease-modifying MS drugs across the 10 payers. The payers on average issued coverage policies for 9.3 drugs. Aetna and Centene were the only payers to issue a coverage policy for all 12 MS therapies; HCSC issued coverage policies for only 2 drugs.

PRACTICAL IMPLICATIONS■■ With respect to drug coverage, payers perform their own assessments and issue their own

coverage policies.

■■ This may result in differences in how payers cover drugs and may affect patients’ access to care.

■■ We examined the coverage policies issued by 10 of the largest private payers for multiple sclerosis drugs and found variation in how the payers covered the drugs and in the evidence that the payers reported reviewing in their coverage policies.


Commercial Payer Coverage of MS Drugs

Each payer issued a coverage policy for alemtuzumab and natalizumab; only 2 payers, Aetna and Centene, issued a coverage policy for mitoxantrone.

Coverage Relative to the Drug’s FDA Approval: Findings Of the 93 cover policies, 42 (45%) were more restrictive than the cor-responding FDA approval, 35 (38%) were consistent, 11 (12%) were less restrictive, and 3 (3%) were mixed (FIGURE 1). On 2 occasions the payer did not cover the drug.

Thirty-six of 51 restrictions (71%) were step-therapy restrictions; 15 (29%) were patient restrictions. An example of a step-therapy restriction was in Anthem’s policy for fingolimod, in which patients were first required to fail an interferon beta, glatiramer acetate, or dimethyl fumarate before having access to fingolimod. An example of a patient restriction was in Independence Health Group’s policy for interferon beta-1b (Extavia), in which the payer did not cover the drug for patients who had experienced a first clinical episode and had MRI features consistent with MS, an FDA-approved indication. Six policies included both a step-therapy and patient restriction.

Evidence Base the Payers Reported Reviewing: FindingsNot all payers reported the evidence that they reviewed in each of their policies. Aetna and Anthem reported reviewing the most studies in their coverage policies, for an average of 15.6 and 7.7 pieces of evidence per policy, respectively. Humana and Centene reported reviewing the fewest studies, for an average of 0.3 and 0.4 studies per policy, respectively (FIGURE 2).

Nine payers reported reviewing RCTs; Anthem reviewed the most RCTs (average of 3.5 per policy), while Humana reported reviewing the fewest (average of 0.2 per policy). Six payers reported reviewing studies that fell into the “other clinical studies” category (average of 0.4 per policy); Anthem reported reviewing the most (average of 2.1 per policy), while UnitedHealthcare reported reviewing the fewest (average of 0.2 per policy). Eight payers reported reviewing clinical guidelines (average of 0.8 per policy); Aetna reviewed the most (average of 2.9 per policy), while Highmark, Humana, Blue Cross Blue Shield Michigan, and UnitedHealthcare reported reviewing the fewest (average of 0.1 per policy). Seven payers reported reviewing clinical reviews (average of

1.3 per policy); Aetna reported reviewing the most clinical reviews (average of 6.9 per policy), while Blue Cross Blue Shield Michigan and UnitedHealthcare reported reviewing the fewest (average of 0.1 per policy). Six payers reported reviewing health technology assessments (average of 0.4 per policy); Aetna reported reviewing the most (average of 2.4 per policy), while Blue Cross Blue Shield Michigan, Blue Cross Blue Shield Florida, and UnitedHealthcare reported reviewing the fewest (average of 0.1 per policy). Aetna reported reviewing 2 cost-effectiveness analyses in its coverage policies and was the only payer to report reviewing evidence of this type.

DISCUSSIONThe multitude of private insurance companies in US healthcare raises the possibility of differential drug coverage. Our study is the first to examine this potential variation in the coverage of disease-modifying MS drugs among US private insurance companies.

We found that coverage policies were most often more restrictive than the corresponding FDA approval and that the most frequent reason that the coverage policy was more restrictive was due to step-therapy restrictions. These findings are consistent with previous research in which we examined private payer coverage of rheumatoid arthritis treatments.5 We found that how the payers covered the included drugs varied, and that no drug was covered the same way by each of the included payers. For example, 6 payers covered alemtuzumab in a manner that was more restrictive than the FDA approval, 3 payers’ coverage policies were consistent with the FDA approval, and 1 payer issued a coverage policy

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Figure 1. Restrictiveness of Payer Coverage of Disease-Modifying Multiple Sclerosis Drugs Relative to the Corresponding FDA Approval


Chambers et al

that was less restrictive than the FDA approval. Both payers that issued a coverage policy for mitoxantrone covered the drug more restrictively than the drug’s corresponding FDA approval, but their determinations differed: Aetna covered mitoxantrone for patients with RRMS but not for patients with chronic progressive disease, while Centene required patients with RRMS to first fail 2 or more alternatives before having access to the drug.

Explanation of Study FindingsThe restrictiveness of the private payer coverage of MS drugs is broadly consistent with other research that has compared payer coverage of drugs and medical devices with their corresponding FDA approval.5,11 While the FDA is charged with ensuring that drugs are “safe and effective,” commercial payers assess whether drugs are “medically necessary” when judging coverage.12 Therefore, while the FDA must rely on evidence of a drug’s safety and efficacy, payers must additionally weigh other factors in their assessment, including benefit-risk trade-offs, the availability of alternatives, costs, and cost-effectiveness.

The variation among private payers’ coverage policies is also consistent with previous research.6 There are several potential reasons for this variation. It may be that payers use different decision-making criteria when judging drug coverage. Indeed, we found that payers report reviewing a different evidence base in their coverage policies, both in terms of the number of studies reviewed and the types

of study reviewed. We found that only 1 payer (Aetna) reviewed evidence that fell into each evidence category. It is likely that some payers more thoroughly report the evidence that they review when formulating their coverage polices than do other payers.

While we found that only Aetna reported reviewing cost-effectiveness analyses in their coverage policies, it is likely that other payers consider economic factors when judging drug coverage.13 It is also likely that volume-based discounts obtained from product manufacturers affect how plans cover drugs; as this information is proprietary, however, we were unable to account for it in this study.14

It may also be that input from customers (eg, large employers) affects drug coverage decisions and contributes to variation among payers.15 The identified variation could be due to payers tailoring their coverage policies to their own beneficiary populations or offering more generous drug coverage to attract enrollees.

Implications Inconsistency among private payer coverage policies may affect the access patients have to MS drugs in different health plans. Differences among drug coverage policies also complicate care delivery, as physicians treating different patients enrolled in a variety of health plans must tailor treatment to the patients’ insurance. It is argued, however, that the variation in use of drugs resultant from differences among coverage policies may help accelerate our understanding of how best to use drugs.16

Drug manufacturers must account for US payers’ evidence requirements when creating clinical development programs for their products. The identified differences in the evidence base that the payers report reviewing point to challenges for manufacturers when attempting to address payers’ evidentiary needs. Greater transparency in how payers use evidence in decision making would allow manufacturers to more readily meet payers’ requirements and potentially speed patients’ access to treatments.

LimitationsNot all payers issued publicly accessible coverage policies for each of the included drugs, a finding consistent with previous research.4-6 Further, our findings may not be generalizable to payers not included in our study. We do not account for the appeals process that is typically available to beneficiaries if coverage of their preferred drugs is denied.

Not all payers reported the evidence that they reviewed in each coverage policy. As noted above, we could account for only the evidence that payers reported reviewing in their coverage policies. It may be that payers review evidence

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Blue Cross Blue Shield Michigan (7 policies, 6 studies)

Blue Cross Blue Shield Florida (11 policies, 45 studies)

Independence Health Group (6 policies, 8 studies)

Centene (12 policies, 5 studies)

Highmark (10 policies, 15 studies)

Aetna (12 policies, 187 studies)

Health Care Service Corporation (2 policies, 6 studies)

Humana (11 policies, 3 studies)

Anthem (11 policies, 85 studies)

UnitedHealthcare (11 policies, 11 studies)

Randomized controlled trials Other clinical studies Clinical guidelines

Clinical reviews Health technology assessments Cost-effectiveness analyses

Figure 2. Proportion of Each Evidence Category Reviewed in Payer Coverage Policies for Disease-Modifying Multiple Sclerosis Drugs


Commercial Payer Coverage of MS Drugs

that they do not report reviewing in their coverage policies. It may also be that payers perform their own analyses, eg, use their own data, which they do not report reviewing.

We did not consider symptomatic and reparative therapies in this study, eg, dalfampridine, a drug indicated to improve walking in patients with MS. We also excluded the recently approved daclizumab because it was first approved by the FDA to treat MS after we obtained the coverage policies for this analysis.17

Researchers in various countries have examined the influence of evidence and other factors in payer coverage of drugs and other medical technologies.18-22 However, in this study, the sample size was insufficient to facilitate an empirical evaluation of the relationship between coverage and the evidence the payers reported reviewing.

CONCLUSIONS Our data illustrate variation in how payers in our sample cover disease-modifying MS drugs and suggest that patients enrolled in different health plans may have differential access to these drugs. We found that the evidence that payers reported reviewing in their coverage policies varied in terms of volume and composition. Uncertainty in payers’ evidence requirements makes it challenging for manufacturers to design clinical programs to support their products because the generated evidence may not be sufficient for all payers. .

Author Affiliations: Tufts University School of Medicine Center for the Evaluation of Value and Risk in Health Institute for Clinical Research and Health Policy Studies, Tufts Medical Center (JC, JA, CW, PR), Boston, MA; Amgen (PR), Thousand Oaks, CA.

Source of Funding: This study was funded by Bayer HealthCare Pharmaceuticals, Inc.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (JC); acquisition of data (JA; CL; PR); analysis and interpretation of data (JC; JA; CL); drafting of the manuscript (JC; JA; CL; PR); critical revision of the manuscript for important intellectual content (JC); statistical analysis (JC; PR); provision of patients or study materials (NA); obtaining funding (JC); administrative, technical, or logistic support (JA; CL; PR); and supervision (JC).

Address Correspondence to: James D. Chambers, PhD, Center for the Evaluation of Value and Risk in Health, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington St., #63, Boston, MA 02111. E-mail: [email protected].

REFERENCES1. Elhauge E. Why we should care about health care fragmentation and how to fix it. In: Elhauge E, ed. The Fragmentation of U.S. Health Care: Causes and Solutions. New York, NY: Oxford University Press; 2010:1-20.

2. Cebul RD, Rebitzer JB, Taylor LJ, Votruba ME. Organizational fragmen-tation and care quality in the US healthcare system. J Econ Perspect. 2008;22(4):93-113.3. Austin DA, Hungerford TL; Congressional Research Service. The market structure of the health insurance industry. Federation of American Scientists website. https://www.fas.org/sgp/crs/misc/R40834.pdf Published May 25, 2010. Accessed August 29, 2016.4. Chambers JD, Chenoweth MD, Neumann PJ. Mapping US commercial payers’ coverage policies for medical interventions. Am J Manag Care. 2016;22(9):e323-e328.5. Chambers JD, Wilkinson CL, Anderson JE, Chenoweth MD. Variation in private payer coverage of rheumatoid arthritis drugs. J Manag Care Spec Pharm. 2016;22(10):1176-1181. doi: 10.18553/jmcp.2016.22.10.1176.6. Chambers JD, Chenoweth M, Thorat T, Neumann PJ. Private payers disagree with Medicare over medical device coverage about half the time. Health Aff (Millwood). 2015;34(8):1376-1382. doi: 10.1377/hlthaff.2015.0133.7. Meckley LM, Neumann PJ. Personalized medicine: factors influenc-ing reimbursement. Health Policy. 2010;94(2):91-100. doi: 10.1016/j.healthpol.2009.09.006. 8. Hresko A, Haga SB. Insurance coverage policies for personalized medicine. J Pers Med. 2012;2(4):201-216. doi: 10.3390/jpm2040201.9. National Association of Insurance Commissioners (NAIC). 2014 Accident and Health Policy Experience Report. NAIC website. http://www.naic.org/prod_serv/AHP-LR-15.pdf. Published 2015. Accessed August 29, 2016.10. The Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products. https://www.accessdata.fda.gov/scripts/cder/drugsatfda/ Accessed August 29, 2016.11. Chambers JD, May KE, Neumann PJ. Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepan-cies remain. Health Aff (Millwood). 2013;32(6):1109-1115. doi: 10.1377/hlthaff.2012.1073.12. Drug Amendments Act of 1962. Public Law 87-781, 76 STAT 780. October 10, 1962. 13. Chambers JD. Do changes in drug coverage policy point to an increased role for cost-effectiveness analysis in the USA? Pharmacoeconomics. 2014;32(8):729-733. doi: 10.1007/s40273-014-0166-6.14. Langreth R, Keller M, Cannon C. Decoding big pharma’s secret drug pricing practices. Bloomberg website. http://www.bloomberg.com/graphics/2016-drug-prices/. Published June 29, 2016. Accessed August 29, 2016.15. Dranove D, Hughes EF, Shanley M. Determinants of HMO formulary adop-tion decisions. Health Serv Res. 2003;38(1 Pt 1):169-190.16. Bailey PG. Medicare and national coverage. Health Aff (Millwood). 2005;24(1):295-296; author reply 296.17. Zinbryta (daclizumab) [highlights of prescribing information]. Cam-bridge, MA: Biogen; May 2016. FDA website. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761029s000lbl.pdf. Accessed August 29, 2016.18. Cerri KH, Knapp M, Fernández JL. Decision making by NICE: examining the influences of evidence, process and context [published correction ap-pears in Health Econ Policy Law. 2014;9(4):435]. Health Econ Policy Law. 2014;9(2):119-141.19. Chambers JD, Chenoweth M, Cangelosi MJ, Pyo J, Cohen JT, Neumann PJ. Medicare is scrutinizing evidence more tightly for national coverage deter-minations. Health Aff (Millwood). 2015;34(2):253-260. doi: 10.1377/hlthaff.2014.1123.20. Charokopou M, Majer IM, Raad J, Broekhuizen S, Postma M, Heeg B. Which factors enhance positive drug reimbursement recommendation in Scotland? a retrospective analysis 2006-2013. Value Health. 2015;18(2):284-291. doi: 10.1016/j.jval.2014.12.008.21. Harris AH, Hill SR, Chin G, Li JJ, Walkom E. The role of value for money in public insurance coverage decisions for drugs in Australia: a retrospec-tive analysis 1994-2004. Med Decis Making. 2008;28(5):713-722. doi: 10.1177/0272989X08315247. 22. Linley WG, Hughes DA. Reimbursement decisions of the All Wales Medicines Strategy Group: influence of policy and clinical and eco-nomic factors. Pharmacoeconomics. 2012;30(9):779-794. doi: 10.2165/11591530-000000000-00000.


NPC

I n response to growing concerns about healthcare costs, during the past few years, we’ve seen an increase in the development and use of value

assessment frameworks. A variety of physician, payer, and patient-based organizations have created these frameworks as a way to measure the value of a healthcare treatment and define value through the lens of specific target audiences.

This list of organizations developing frameworks is growing, with the Institute for Clinical and Economic Review (ICER), Sloan Kettering Memorial Cancer Center (DrugAbacus), the American Society for Clinical Oncol-ogy, the American College of Cardiology/American Heart Association, the National Comprehensive Cancer Network (NCCN), FasterCures/Avalere, and the National Health Council among those that have created assessment tools.

In the United States, value assessments are a new and evolving area and have the potential to significantly affect payer coverage and reimbursement policies as well as the resulting access to treatments for patients. With this potential impact in mind, the National Pharmaceutical Council (NPC) developed a set of patient-centered guiding practices that can serve as a guidepost for framework developers and users. Establishing and adhering to guiding practices can help ensure that value assessment frameworks are effective tools for advancing patient care and achieving better outcomes for patients rather than well-intentioned but flawed tools that impede such progress.

At a high level, NPC’s guiding practices outline 6 main areas of focus that should guide framework developers and assessments:

w Assessment process: Stakeholder input and feedback—especially from patients—should be incorporated throughout the assessment process, from the announcement of topics to be examined through the entire review cycle. Current frameworks

still vary widely in the extent to which they embed patients in the process. Patients are ultimately affected by the value-based decisions of other stakeholders, so it is critically important to engage with patients and consider their perspectives throughout the framework development and assessment processes.

As part of the assessment process, methodologi-cal experts also need to be involved. As frameworks use more advanced methods to evaluate different types of evidence, conduct extensive economic modeling, and serve more diverse users, they should revisit their mix of expertise and ways in which experts are involved in the processes. Additionally, assessments should be reviewed regularly to keep pace with continued medical innovation and updated evidence.

w Methodology: Assessments should focus on all aspects of the healthcare system. The majority of the focus is still on drugs and biologics, leaving stakeholders without value assessments for devices, diagnostics, surgical procedures, and other interven-tions. Frameworks should use established methods, as well as transparent models and assumptions, and include guidance to help users understand key drivers behind the results.

w Benefits: Assessments should include a broad array of factors that are important to patients and society, such as quality of life, the ability to work, and a reduction of the burden on caregivers. Assessments should also consider individual treatment effects and view the value of a treatment over the long-term horizon.

w Costs: All healthcare costs and offsets over time should be considered, and these costs

Guiding Practices for Patient-Centered Value AssessmentDan Leonard, MA, President, National Pharmaceutical Council


Guiding Practices for Patient-Centered Value Assessment

should be accurate and relevant to the user of the framework. There is currently wide variation among the value frameworks with respect to cost analyses and assumptions. This highlights the importance of transparency in the assumptions, evidence, and methods used, as well as recognition of their impact on the findings of value assessments and how these findings will be applied.

w Evidence: All the sound, high-quality evidence that is currently available should be used for the assessment. It should be gathered and synthesized in a transparent and robust manner, using accepted methods.

Unfortunately, this is an area in which some frameworks are still struggling. Frameworks rely on evidence about treatments that is available at a given point in time, which can be limited to a particular population or outcome. Evidence evolves over time, providing a greater understanding of how a product works in the real world or in patients with multiple comorbidities. While payers routinely update their coverage decisions as this new evidence evolves, ICER assessments or DrugAbacus inputs, for example, are a static representation of evidence at a point in time. ICER does not conduct routine updates to its assess-ments as new findings become available; in fact, it has conducted a supplemental “brief evidence update” only once. By contrast, NCCN regularly updates its assessments, which it calls evidence blocks, as new evidence becomes available. Outdated information could hurt, rather than help, patients.

w Dissemination and utilization: Assessments should be clearly labeled for their intended use and should be easy for users to interpret and disseminated only after they are finalized. If a framework’s results are misinterpreted, patient access to appropriate treatments could be seriously affected.

It’s notable that some of the existing frameworks and the more recently developed ones, such as FasterCures/Avalere, are incorporating these guiding practices into their value assessment frameworks and processes. Developers are recognizing that these are key components to achieving a more complete and meaningful picture of the value of a health treatment.

Importantly, there should be a broad array of frameworks in healthcare decision making. Most stakeholders understand that taking a one-size-fits-all approach and relying on a single framework to evaluate a healthcare treatment or intervention is not sufficient to inform care for diverse populations. Utilizing multiple frameworks and other decision-making tools can provide far more information as well as important and different perspectives, such as those of physicians, consumers, and especially patients.

It is becoming increasingly clear, though, that frameworks will continue to evolve and be part of the landscape. Our dialogue about frameworks in the United States will be ongoing and will require input from a variety of stakehold-ers. Setting forth guiding practices can help ensure that frameworks are effective tools for decision makers who support value in patient care and outcomes rather than well-intentioned but flawed tools that impede it.


C hemotherapy-induced nausea and vomiting (CINV) is among the most common and distressing adverse events associated with chemotherapy.1,2 Experienced by up to 80% of patients undergoing

chemotherapy,3,4 CINV can have physical, mental, compliance, and financial impacts on patients. Multiple studies have demonstrated that without appropriate management, nausea has a significant impact on health-related quality of life (HRQOL).4-6 CINV can also increase the risk of electrolyte imbalance and dehydration, anorexia, paresthesia, malnutrition, and gastrointestinal complications. These can lead to hospitalization, the need for hydration therapy, and decreased HRQOL, resulting in reduced participation in activities of daily living as well as increased health-related costs.5-9 In a study of 178 patients undergoing chemotherapy, 37.2% of all patients indicated that CINV reduced their daily functioning, while 90% of patient subjects with poorly managed CINV disclosed a significant, negative impact on daily functioning.5

CINV can also affect compliance and adherence to chemotherapy. Patients who experience CINV may become noncompliant with treatment, resulting in delays in chemotherapy administration, dose reduction, or interruption of therapy, thereby potentially affecting treatment efficacy.10-15 Such delays and termination of treatment are recognized by healthcare providers. In a survey of more than 2000 clinicians, up to 32% of the hematology/oncology

Managing Chemotherapy-Induced Nausea and Vomiting (CINV) to Improve Patient CareThis activity is supported by educational grants from Eisai Inc. and Tesaro, Inc.

EDUCATIONAL OBJECTIVESAt the completion of this activity, the participant will be able to:

■■ Explore standard and emerging treatment options to manage chemotherapy-induced nausea and vomiting (CINV)

■■ Explain appropriate monitoring parameters based on chemotherapy and CINV regimen

■■ Determine the safety and efficacy of CINV agents for different patient types

■■ Provide information needed to make antiemetic formulary decisions

TARGET AUDIENCE: Pharmacists and pharmacy directors

ACTIVITY TYPE: Application

RELEASE DATE: September 12, 2017

EXPIRATION DATE: September 12, 2018

ESTIMATED TIME TO COMPLETE ACTIVITY: 2.0 hours

FEE: This lesson is offered for free at pharmacytimes.org

Faculty

Sally Yowell Barbour, PharmD, BCOP, CPP, FHOPA

Director of Oncology Pharmacy Programs

Duke University Medical Center

Durham, North Carolina

Patrick Medina, PharmD Professor of MedicineStephenson Cancer CenterUniversity of OklahomaOklahoma City, Oklahoma

Medical Writers

Thomas J. Cook, PhD, RPh

Freelance Medical WriterStewartsville, New Jersey

Joanne FaysalMedical WriterSouth Palm Beach, Florida

DisclosuresTHE FOLLOWING CONTRIBUTOR HAS RELEVANT FINANCIAL RELATIONSHIPS WITH COMMERCIAL

INTERESTS TO DISCLOSE:

FacultySally Yowell Barbour, PharmD, BCOP, CPP

Grant/research support: Tesaro, Inc.

THE FOLLOWING CONTRIBUTORS HAVE NO RELEVANT

FINANCIAL RELATIONSHIPS WITH COMMERCIAL INTERESTS TO DISCLOSE.

Faculty/Medical WritersPatrick Medina, PharmD; Thomas J. Cook, PhD, RPh;

Joanne Faysal

PHARMACY TIMES CONTINUING EDUCATION™ PLANNING STAFF

David Heckard; Maryjo Dixon, RPh; Jyoti Arya, PharmD, RPh; Donna Fausak; and Susan Pordon

Pharmacy Times® Editorial StaffKirk McKay

An anonymous peer reviewer was part of the content validation and conflict resolution and has no relevant financial relation-

ships with commercial interests to disclose.

Pharmacy Times Continuing Education™ is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 2.0 contact hours (0.20 CEUs) under the ACPE universal activity number 0290-0000-17-143-H01-P. The activity is available for CE credit through September 12, 2018.

CONTINUING EDUCATION


Managing CINV to Improve Patient Care

healthcare provider survey responders indicated that CINV prompted a delay or termination of chemotherapy in their patients in the prior year.16

In addition to clinical concerns, the economic impact of CINV can be substantial. Haiderali et al estimated that the average total cost for CINV was $778.58 per patient from the day of administration through the 5 days following the first cycle of chemotherapy, with higher costs for patients with more severe CINV.5 One retrospective cohort analysis assessed the cost of CINV in 5912 adult patients diagnosed with breast, lung, or colon cancer who were newly treated with single-day highly or moderately emetogenic chemotherapy (HEC or MEC) and received a prophylactic 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist.17 CINV affected up to 24% of patients on HEC and up to 32% on MEC, with nearly double the overall healthcare costs for patients with CINV. The mean total healthcare costs in the first cycle for patients with CINV were $18,836, compared with $9582 for patients without CINV (P <.001).17 Similar results were seen in another retrospective analysis of medical claims of 2018 people with cancer treated with HEC or MEC.18 This study found that an estimated increase of $1300 per patient in monthly medical costs and an increase of $433 per patient per month in indirect costs could be attributed to uncontrolled CINV.18 Data have also shown that CINV-related hospitalizations and office visits were common in the first month after chemotherapy.19 As CINV remains both a clinical and economic concern for patients with cancer, appropriate management of these patients should be a priority for clinicians who care for them.

CINV BACKGROUNDCINV DefinitionsCINV can be categorized as acute, delayed, anticipatory, breakthrough, or refractory. Acute CINV occurs from 0 to 24 hours after chemotherapy initiation and is often the most intense after 5 to 6 hours.20-22 Delayed-onset CINV typically occurs 24 hours to 5 days after chemotherapy initiation and is often most intense at 48 to 72 hours.20-22 Several studies have shown delayed CINV is more common than acute CINV and often occurs in patients receiving carboplatin, cisplatin, cyclophosphamide, and doxorubicin.6,22-24 Studies have also shown that the incidence of CINV in the first cycle of chemotherapy is predictive for CINV in subsequent cycles.25 Importantly, delayed CINV can occur in patients who do not experience acute CINV, and a lack of control of CINV in the acute phase is often predictive of an inability to control delayed CINV.8 Anticipatory CINV occurs prior to the next chemotherapy treatment, often because of a previous negative experience with chemotherapy. Breakthrough

CINV occurs regardless of administration of antiemetic agents, often necessitating the use of rescue therapy, and refractory CINV is that which does not respond to antiemetic prophylaxis or rescue treatment.22 Patient factors that tend to increase the risk of CINV include a history of nausea and vomiting (eg, motion sickness, pregnancy-induced nausea and vomiting), age (<50 years old), female gender, and low alcohol consumption.26-29 However, the most important determinant of the incidence of CINV is the type and dosage of chemotherapy, administration route and/or schedule, and the emetogenicity of the chemotherapeutic agent.22

Emetic Potential of Chemotherapeutic AgentsChemotherapeutic agents have been classified according to the associated risk of inducing acute nausea and vomiting: high (HEC), moderate (MEC), low, and minimal emetic risk. HEC agents, which include cisplatin, dacarbazine, carboplatin (area under the concentration time curve [AUC] ≥4 mg/mL/min) and high-dose cyclophosphamide (≥1500 mg/m2), cause CINV in >90% of patients when untreated with antiemetics. Of note, carboplatin AUC ≥4 is classified as a high risk by NCCN guidelines but as a moderate risk by ASCO guidelines. Approximately 30% to 90% of patients experience CINV after receiving MEC agents such as carboplatin (AUC <4 mg/mL/min), cyclophosphamide (<1500 mg/m2), anthracyclines, and oxaliplatin.22,30 Low emetic risk agents including etoposide, methotrexate, taxanes, gemcitabine, pemetrexed, lenalidomide, and temsirolimus are associated with CINV in 10% to 30% of patients, and minimal emetic risk agents, which include bleomycin, bevacizumab, vincristine, and fludarabine, among others, cause CINV in <10% of patients.22,30

Effects of CINVCINV can affect patients not only physically but also mentally and financially. Dehydration, anorexia, and electrolyte imbalance often accompany CINV, which can lead to hospitalization, the need for hydration therapy, and reduced treatment compliance.7,8,30 CINV can have a major impact on patient HRQOL, resulting in reduced participation in activities of daily living as well as health-related costs.5,6 The Anti-Nausea Chemotherapy Registry (ANCHOR) study showed that persistent nausea can have a bigger impact on HRQOL than vomiting, and a greater reduction in HRQOL was experienced by patients receiving HEC compared with MEC.6 Whether or not associated with CINV, quality of life (QOL) may have prognostic value for overall survival of cancer patients.31-33 As such, QOL monitoring is important as part of comprehensive patient management, which can result in improved changes in antiemesis treatment


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and potentially improved QOL outcomes.34 While there are many assessment questionnaires available to broadly measure QOL in patients with cancer, several are designed specifically to assess the impact of CINV on QOL.

Assessment of QOLThe Functional Living Index–Emesis (FLIE) is a validated 7-point visual analog scale tool that includes 9 questions related to the effects of nausea and vomiting on activities of daily living as well as social and emotional functioning for up to 5 days after chemotherapy.35,36 The Morrow Assessment of Nausea and Emesis (MANE) is a 17-item questionnaire used to assess the severity, duration, and frequency of CINV as well as adherence to and efficacy of antiemesis treatment.37 The Rhodes Index for Nausea, Vomiting, and Retching is an 8-item questionnaire that covers CINV occurring only within the last 12 hours and is, therefore, not useful to measure the effects of delayed CINV on QOL.38 While the FLIE and MANE assessment tools are reliable and valid, barriers to their consistent use include the overall length of the tool and the required time to complete them.38,39 The Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool is an 8-item questionnaire regard-ing nausea and vomiting that is meant to be completed once during each cycle of chemotherapy; other CINV assessment tools are designed to be completed more often.40

TREATMENT OF CINVSeveral categories of drugs are available to treat CINV, including dopamine receptor antagonists, corticosteroids, serotonin (5-HT3) receptor antagonists, and neurokinin-1 (NK1) receptor antagonists, among others.

A Historical PerspectiveDopamine receptor antagonists including metoclopramide, haloperidol, and prochlorperazine were among the first agents to treat CINV and are still recommended for the treatment of low- or minimal-emetic–risk chemotherapy, as well as breakthrough and refractory CINV.22 Adverse events associated with dopamine antagonists include sedation, dystonia, akathisia, and hypotension.

Corticosteroids, including dexamethasone and meth-ylprednisolone, were the second group of drugs used for the treatment of both acute and delayed CINV. Early studies provide evidence indicating that corticosteroids are equivalent or superior compared with dopamine receptor antagonists for the prevention or management of CINV.41-44 The addition of dexamethasone was found to increase the antiemetic efficacy of the 5-HT3 receptor antagonists.45-47 As such, antiemetic combinations that include corticosteroids,

specifically dexamethasone, are now the mainstay treatment for acute and delayed CINV.22,48,49

5-HT3 Receptor AntagonistsSeveral 5-HT3 antagonists are approved for the prevention of CINV in patients receiving HEC and MEC including dolasetron (oral route only), granisetron, ondansetron, and palonosetron.22 These agents work by blocking the binding of serotonin to 5-HT3 receptors in the chemoreceptor trigger zone and solitary tract nucleus in the central nervous system.50 Dolasetron, granisetron, and ondansetron are first-generation 5-HT3 antagonists that are associated with generally similar efficacy.51-55 Among patients receiving cisplatin (>50 mg/m2), single agent 5-HT3 antagonists can reduce acute CINV in 40% to 60% of patients, and this increases to 60% to 90% when dexamethasone is added.51-55 Adverse events that commonly occur with 5-HT3 antagonists include headache, gastrointestinal effects, and elevation of liver aminotransferase levels.52,56-58 When using first-generation 5-HT3 antagonists (ie, dolasetron, granisetron, and ondansetron), clinicians should be aware of the potential for QT interval prolongation.51-55 Granisetron carries a caution for use in susceptible patients,58 while ondansetron (single doses >16 mg) and dolasetron are contraindicated in patients with long QT syndrome.56,57

Evidence suggests 5-HT3 antagonists are more effective for the prevention of acute emesis than delayed emesis, potentially because of a short half-life.3,59 Palonosetron is a second-generation 5-HT3 antagonist that has a stronger affinity for 5-HT3 receptors and a longer half-life (~40 hours). A meta-analysis of 4 studies in adults and 1 study in children and a retrospective study in adults of 5-HT3 antagonists found that palonosetron was more effective for the prevention of delayed CINV in patients receiving MEC and HEC compared with other 5-HT3 antagonists.60,61 A pooled analysis of 4 randomized, double-blind, phase 3 trials (palonosetron 0.25 mg or 0.75 mg compared with dolasetron 100 mg, granisetron 40 mcg/kg, or ondansetron 32 mg) found palonosetron was more effective in preventing both delayed and acute CINV.62

In addition to the common intravenous (IV) and oral routes of administration, 2 relatively new formulations of the first-generation 5-HT3 antagonist, granisetron, are also available. The subcutaneous (SC) product is a polymer-based, extended-release formulation for administration at least every 7 days63 and can maintain therapeutic levels for ≥5 days.64 The efficacy of the SC granisetron formulation compared favorably with ondansetron (as part of a 3-drug antiemetic regimen) and palonosetron (as an individual agent) in separate trials of patients receiving



MEC or HEC.65,66 When used in a combination regimen that included fosaprepitant and dexamethasone, a higher percentage of HEC patients receiving granisetron SC experienced delayed-phase complete response compared with ondansetron IV (64.7% vs 56.6% for granisetron and ondansetron, respectively [95% CI, 1.7–14.4; P = .014]).66 In the single-agent trial, granisetron SC at doses of 250 mg and 500 mg were noninferior to palonosetron in preventing acute CINV in patients with MEC or HEC therapy. For delayed CINV, granisetron SC was noninferior to palonosetron in MEC regimens, while noninferiority could not be analyzed in HEC regimens because parameters for palonosetron in preventing delayed CINV in HEC were not set at the time of the study.65 In both of the cited studies, granisetron SC had similar safety and adverse event profiles compared with the respective comparator drug.65,66 It is critical to note that the granisetron SC extended-release formulation cannot be substituted for the IV formulation and vice versa. The other newer formulation of granisetron is a transdermal patch that delivers the drug over a 7-day interval and is approved for treating CINV for up to 5 consecutive days in patients receiving MEC or HEC.67 In an open-label study with 196 patients, the transdermal granisetron patch was found to be noninferior to palonosetron for the prevention of acute CINV in patients receiving MEC.68 The clinical studies provide support for the use of granisetron transdermal and granisetron SC in acute and delayed CINV, respectively, in MEC regimens.

NK1 Receptor AntagonistsFour NK1 receptor antagonists are currently available: aprepitant, fosaprepitant, rolapitant, and netupitant. The NK1 receptor antagonists prevent emesis by blocking substance P and the NK1 receptor. Aprepitant is an oral NK1

antagonist approved in combination with dexamethasone and a 5-HT3 receptor antagonist for the prevention of acute and delayed CINV in patients receiving HEC and MEC.69 Compared with ondansetron plus dexamethasone, aprepitant plus dexamethasone was superior in preventing acute and delayed CINV in patients receiving cisplatin-based chemotherapy.70 Several trials demonstrated that the addition of aprepitant to a 5-HT3 receptor antagonist and dexametha-sone is significantly more efficacious in controlling acute and delayed CINV in patients receiving HEC compared with a 5-HT3 receptor antagonist and dexamethasone alone.71-77 Common adverse events associated with aprepitant that occurred in more than 10% of patients in clinical trials include diarrhea, anorexia, constipation, and nausea; however, the incidence of these adverse events was similar among patients receiving placebo.76 Also, more patients

receiving aprepitant experienced fatigue, dizziness, diarrhea, and hiccups compared with placebo.76 Aprepitant is a moderate CYP3A4 inhibitor, and it is contraindicated in patients receiving pimozide, terfenadine, astemizole, or cisapride.69 It is also contraindicated in patients receiving warfarin. Caution should be used when using aprepitant in patients receiving chemotherapy agents that are metabolized by CYP34A, including docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine.69 When aprepitant is coadministered with dexamethasone, dose adjustments of dexamethasone are required because aprepitant can double the area under the curve of dexamethasone.78-81

Fosaprepitant is a prodrug of aprepitant adminis-tered intravenously.69 In a study of ondansetron plus dexamethasone in combination with either a 3-day regimen of aprepitant or a 1-day regimen of fosaprepitant, fosaprepitant was found to be noninferior to aprepitant for the prevention of acute and delayed CINV in patients receiving cisplatin-based chemotherapy.82 Studies have also shown that adding single-dose fosaprepitant to a 5-HT3 antagonist and dexamethasone is more efficacious in preventing acute and delayed CINV in patients receiving HEC compared with 5-HT3 plus dexamethasone alone.83,84 A phase 3 trial evaluating ondansetron and dexamethasone ± fosaprepitant in patients receiving MEC demonstrated that the addition of fosaprepitant was superior to the ondansetron/dexamethasone regimen in preventing CINV in the delayed and overall phases, while there was no statistically significant difference between regimens in the acute phase.85 Treatment with fosaprepitant was well tolerated; the majority of adverse events did not vary significantly between patients receiving fosaprepitant and those receiving placebo.83,85 Common adverse events among patients in both groups included diarrhea, constipation, and fatigue. More patients receiving fosaprepitant experienced infusion-related adverse events, most of which were mild to moderate in severity.

Rolapitant is an oral NK1 antagonist approved in combination with dexamethasone and a 5-HT3 recep-tor antagonist for the prevention of delayed CINV in patients receiving HEC and MEC.86 In combination with ondansetron and dexamethasone, rolapitant was superior to ondansetron and dexamethasone alone in preventing acute and delayed CINV in patients receiving HEC or MEC over multiple cycles of chemotherapy.87,88 In combination with granisetron and dexamethasone, rolapitant was more effective than granisetron and dexamethasone alone in preventing delayed CINV in patients receiving MEC.89 Studies also indicate rolapitant is well tolerated, with


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fewer than 10% of patients experiencing treatment-related adverse events.87,89 The most common adverse events associated with rolapitant therapy include neutropenia, hiccups, decreased appetite, and dizziness.86 Rolapitant can inhibit CYP2D6 and should be avoided in patients receiving pimozide, as the combination may result in QT prolongation.86 In addition, strong CYP3A4 inducers such as rifampin can reduce the efficacy of rolapitant by decreasing plasma concentrations because rolapitant is metabolized by CYP3A486; however, rolapitant is neither an inhibitor nor an inducer of CYP3A4.90

Netupitant is an oral NK1 antagonist that is currently available in a fixed-dose combination with palonosetron (NEPA) for the prevention of acute and delayed CINV in patients receiving HEC and MEC.91 In a phase 3 study, NEPA in combination with dexamethasone was compared with palonosetron plus dexamethasone for the prevention of CINV after MEC.92 Results indicated that NEPA was superior to palonosetron plus dexamethasone in preventing acute and delayed CINV. NEPA plus dexamethasone has also been shown to effectively prevent acute and delayed CINV in patients receiving HEC.93 Common adverse events associated with NEPA include headache, constipation, asthenia, dyspepsia, fatigue, hiccups, and erythema.92,93 Severe adverse events reported in clinical trials include neutropenia and leukopenia.93 Importantly, netupitant is a moderate inhibitor of CYP3A4, and caution is advised when prescribing NEPA to patients receiving concomitant drugs that are metabolized by CYP3A4, including dexa-methasone, benzodiazepines, oral contraception, and some chemotherapeutics. In addition, NEPA should be avoided in patients with renal or hepatic impairment.91 As dexamethasone is commonly coadministered in antiemetic regimens, the dose of dexamethasone should be reduced with concomitant administration with NEPA.94,95

OlanzapineOlanzapine is an oral antipsychotic that interacts with numerous receptors, including dopamine, serotonin, histamine, adrenergic, and muscarinic receptors.96 Several trials provide evidence for the efficacy of olanzapine as an antiemetic among patients receiving chemotherapy. In a phase 3 trial, patients receiving HEC were treated with palonosetron and dexamethasone combined with either olanzapine or aprepitant for the prevention of CINV.97 Data indicate the 2 combinations were similar in their ability to prevent CINV; however, it was noted that the olanzapine combination was better able to control nausea. In the Phase III Trial of Olanzapine Combined With NK1, 5HT3, and Dexamethasone (Alliance A221301), olanzapine

was combined with aprepitant, a 5-HT3 antagonist, and dexamethasone in patients receiving HEC. Compared with control treatment (ie, aprepitant + a 5-HT3 antagonist + dexamethasone), olanzapine was more efficacious in controlling acute and delayed CINV.98 Olanzapine was also found to be more effective than metoclopramide for treatment of breakthrough nausea and vomiting.99 Adverse events associated with olanzapine-based combinations include fatigue, hyperglycemia, headache, dry mouth, and diarrhea.100,101 Caution should be used in patients receiving concomitant metoclopramide or haloperidol because of an increased risk of extrapyramidal symptoms.96 Dose reduction to 5 mg can be considered if the standard 10-mg dose causes excess sedation.98,102

EVIDENCE-BASED TREATMENT OF CINVGuidelines for the prevention and treatment of CINV are available from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO).22,30,48,49 In general, standard antiemetic guidelines recommend that antiemesis treatment be initiated before and throughout the first 24 hours following the administration of chemotherapy to prevent acute CINV, with treatment scheduled throughout the duration of chemotherapy to prevent delayed CINV.22,48 Antiemetics of differing mecha-nisms of action are also recommended. In patients receiving combination chemotherapy, the potency of the antiemetic regimen should align with the chemotherapeutic agents with the highest risk of CINV.22,48 The recommendations within the guidelines vary based on the emetic risk group of the chemotherapeutic agents administered.

Treatment of Acute and Delayed CINVFor the best outcomes in patients receiving HEC, a combina-tion of 3 to 4 antiemetic agents of differing mechanisms of action (eg, NK1 receptor antagonists, 5-HT3 receptor antagonists, dexamethasone, olanzapine) is recommended for the treatment of acute CINV, while a combination of 2 to 3 drugs is recommended for patients receiving MEC, and monotherapy is recommended for patients receiving low-emetic chemotherapy (TABLE22,30,48). Since no specific regimen is recommended for patients receiving minimal-risk chemotherapy,22 practitioners may use their best clinical judgment. In addition, MASCC/ESMO recommends a combination of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant in patients receiving high-dose chemotherapy for stem cell transplant as well as for patients receiving multiday chemotherapy.103 The regimens for preventing



delayed CINV require administration of antiemetic agents on days 2, 3, and generally day 4 as well. Dexamethasone, while not a preferred agent, is a com-mon drug for delayed CINV for HEC and MEC. Other agents include aprepitant and olanzapine.22

Treatment of Breakthrough and Refractory CINVWhile guidelines for the treatment of breakthrough CINV vary, the NCCN and MASCC generally recommend to add a drug to the current regimen, where the added agent is from a different drug class.22,30 In the NCCN guidelines, olanzapine is a preferred agent for breakthrough CINV when olanzapine is not part of the original CINV regimen.22 ASCO guidelines for breakthrough CINV include adding olanzapine, if the patient has not previously received olanzapine. Patients who have previously received olanzapine may be offered drugs from a different class in addition to current prophylactic treatment.48

Refractory CINV presents additional challenges. The highest practical level of antiemetic therapy is generally recommended from the beginning of chemotherapy treatment. When CINV occurs despite optimal antiemetic therapy (ie, refractory CINV), options include increasing antiemetic therapy for subsequent cycles,22 using a different 5-HT3 receptor antagonist, and adding a dopamine antagonist or benzodiazepine.30 Olanzapine and cannabinoids may also be considered for the treatment of refractory CINV.22 Dronabinol and nabilone are 2 oral cannabinoids that are FDA approved for CINV in patients who have not adequately responded to standard antiemetic therapy. Adverse events associated with cannabinoids include sedation, dizziness, dysphoria, paranoia, hallucinations, and arterial hypotension.104,105

Emphasis on PreventionDespite several guidelines available, adherence to these guidelines is variable, and an increased emphasis on CINV needs to occur. Although a variety of treatments including serotonin and neurokinin-1 receptor antagonists are available to treat CINV, acute CINV is often inadequately controlled in approximately 35% of patients.24 Several factors associated with poor control of CINV include underestimating the incidence of CINV as well as the effectiveness of antiemet-ics, poor compliance with evidence-based guidelines, the high cost of antiemetics, and a lack of knowledge or

familiarity regarding guidelines.16,23,24,106-108 Several studies have found that roughly 40% of clinicians did not follow guidelines when making treatment decisions related to CINV prophylaxis.106,107 Following guideline-based treatment resulted in significant reductions in the occurrence of CINV and improved outcomes.106,107,109 In addition, nonadherence to guidelines, especially for delayed CINV, can result in the over- and under-prescribing and dosing of antiemetics.110

PHARMACIST’S ACTIVE ROLE IN THERAPY MANAGEMENTAs part of the multidisciplinary care team, pharmacists, formulary decision makers, and managed care professionals have an opportunity to have a significant impact on patient care. Many of these healthcare professionals play key roles in developing and/or implementing guidelines that provide guidance for treatment selection that are specific to the institution or patient population they serve. Ensuring that appropriate guidelines are in place for chemotherapy treatment selection and that emetogenicity of treatment is included can help in preventing or mitigating adverse events. Institutional guidelines should include:

w Using evidence-based strategies for the treatment and management of CINV through a multidisci-plinary approach

w Patient-centered care and outcomes achieved in a cost-effective manner using evidence-based care and data-supported best practices

w Value-based care that includes prevention or mitigation of adverse events such as CINV

Through a multidisciplinary team approach, pharmacists also play a key role in the ongoing assessment of a patient’s

Table. Abridged Guidelines for the Prevention of Acute or Delayed CINV22,30,48

Chemotherapy Emetic Risk Group

Acute CINV – Antiemetic Regimensa

Delayed CINV – Antiemetic Regimensa

High

5-HT3 + NK1 + DEX 5-HT3 /NK1 combo + DEX

5-HT3 + DEX + NK1 + olanzapineOlanzapine + palonosetron + DEX

DEX + NK1

DEXOlanzapine

Moderate

5-HT3 + DEX5-HT3 + NK1 + DEX

5-HT3 /NK1 combo + DEXOlanzapine + palonosetron + DEX

DEX or 5-HT3 or olanzapine

Low 5-HT3 , DEX, DRA, or olanzapine DEX, DRA, or 5-HT3

Minimal Per clinical judgment Per clinical judgment

DEX: dexamethasone; DRA: dopamine receptor antagonists; NK1: NK1 receptor antagonists; 5-HT3: 5-HT3 receptor antagonists.aOrder of regimens or agents does not indicate preferential status. Also, the delayed regimen depends on which acute regimen was used.


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risk factors for CINV and response to therapy.111 As the incidence of delayed CINV is often underestimated, it is important that clinicians, including pharmacists, closely monitor patients throughout the entire treatment period.23 On an ongoing basis, pharmacists can ensure that the goals of treatment—length of therapy, appropriate use of medica-tions, and the importance of adherence to treatment—are discussed with the patients and within the multidisciplinary team to ensure that patients are appropriately managed and educated about their treatment. Effective patient education by pharmacists may help ensure better self-management and treatment of CINV.

Pharmacists function as an extension of the healthcare practice and can therefore alleviate some of the burden placed on other members of the healthcare team by ensuring that patients understand and have realistic expectations of the treatment and potential adverse effects. This includes addressing potential drug–drug interactions for patients with comorbid conditions or those on polytherapy. Additionally, when involved in planning therapy and supportive care, pharmacists can help assist patients with inquiries about plan benefits, prior authorizations, and co-pays. Because many of these agents are expensive and require prior authorization, involving pharmacists in the decision-making process is ideal so that financial issues can be identified before initiation of therapy. Research suggests that pharmacist intervention can reduce costs of antiemetics by 16% in outpatient clinics.112 Further, knowledge of cost and drug efficacy data is relevant to formulary decision mak-ers to ensure that drug therapy benefits are maximized and cost is minimized.

FORMULARY DECISIONSThe antiemetic guidelines provide a foundation for making appropriate formulary decisions. Common formulary decision processes113 would apply to the majority of antiemetic drugs, as there are no biologic or specialty drugs in the guidelines. Beyond representative compounds from each class, formulary decisions will likely focus on which and how many 5-HT3 and NK1 inhibitors to include, as they are the most recent additions to antiemetic therapy. The first-generation 5-HT3 inhibitors are similar in their duration of action and efficacy, while the second-generation 5-HT3 inhibitor, palonosetron, has a longer half-life. Other considerations involve the potential inclusion of the 5-HT3/NK1 combination product and newer formulations of established drugs. Newer formulations of established drugs would not be automatically added to a formulary, pending clinical and pharmacoeconomic analyses. In addition to the standard cost of the drug, the economic

impact of CINV incidence is an important factor to consider along with how drug efficacy reduces that impact. When available, cost-benefit analyses that are independent of industry sponsorship may be helpful when rounding out the list of available antiemetics in a formulary.

SUMMARYCINV is a well-known and common adverse event in cancer chemotherapy that is dreaded by patients and caregivers. With multiple effects on the well-being of patients (eg, mental, physical, financial), the prevention, treatment, and control of CINV is critical for optimizing patient and therapeutic outcomes. Multiple antiemetic guidelines provide pharmacists with direction on how to manage and recommend antiemetic therapy regimens for each emetogenic risk type of chemotherapy (HEC, MEC, low, and minimal). With a variety of antiemetic compounds, CINV can be approached from multiple therapeutic mechanisms. The expertise of pharmacists can help provide critical support in the prevention and treatment of CINV. Formulary decisions could be driven not only by the cost of medication therapy but also by the cost savings in preventing incidence of CINV.

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102. Hashimoto H, Yanai T, Nagashima K, et al. A double-blind randomized phase II study of 10 versus 5 mg olanzapine for emesis induced by highly emetogenic chemotherapy with cisplatin. J Clin Oncol. 2016;34(15 sup-pl):10111. doi: 10.1200/JCO.2016.34.15_suppl.10111.103. Einhorn LH, Rapoport B, Navari RM, Herrstedt J, Brames MJ. 2016 up-dated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. Support Care Cancer. 2017;25(1):303-308. doi: 10.1007/s00520-016-3449-y.104. Tramèr MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001;323(7303):16-21. 105. Ahmedzai S, Carlyle DL, Calder IT, Moran F. Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy. Br J Cancer. 1983;48(5):657-663. 106. Gilmore JW, Peacock NW, Gu A, et al. An-tiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting in US community oncology practice: INSPIRE study. J Oncol Pract. 2014;10(1):68-74. doi: 10.1200/JOP.2012.000816.107. Affronti ML, Schneider SM, Herndon JE, Schlundt S, Friedman HS. Adher-ence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice. Support Care Cancer. 2014;22(7):1897-1905. doi: 10.1007/s00520-014-2136-0.108. Wood M, Hall L, Hockenberry M, Borinstein S. Improving adherence to evi-dence-based guidelines for chemotherapy-induced nausea and vomiting. J Pe-diatr Oncol Nurs. 2015;32(4):195-200. doi: 10.1177/1043454214563403.109. Abunahlah N, Sancar M, Dane F, Özyavuz MK. Impact of adherence to antiemetic guidelines on the incidence of chemotherapy-induced nausea and vomiting and quality of life. Int J Clin Pharm. 2016;38(6):1464-1476. doi: 10.1007/s11096-016-0393-3.110. Burmeister H, Aebi S, Studer C, Fey MF, Gautschi O. Adherence to ESMO clinical recommendations for prophylaxis of chemotherapy-induced nausea and vomiting. Support Care Cancer. 2012;20(1):141-147. doi: 10.1007/s00520-010-1079-3.111. Barbour SY. The pharmacist’s perspective on the management of CINV. Medscape website. www.medscape.org/viewarticle/729999. Published 2010. Accessed June 6, 2017.112. Iihara H, Ishihara M, Matsuura K, et al. Pharmacists contribute to the improved efficiency of medical practices in the outpatient can-cer chemotherapy clinic. J Eval Clin Pract. 2012;18(4):753-760. doi: 10.1111/j.1365-2753.2011.01665.x.113. Schiff GD, Galanter WL, Duhig J, et al. A prescription for improving drug formulary decision making. PLoS Med. 2012;9(5):1-7. doi: 10.1371/journal.pmed.1001220.


Barbour | Medina

1. The first-generation 5-HT3 receptor antagonists have a potential for QT interval prolongation. Two of the 3 drugs in this class are contraindicated in patients with long QT syndrome. Which of the following drugs are contraindicated in patients with long QT syndrome?

A. Palonosetron and ondansetronB. Olanzapine and dolasetronC. Granisetron and dolasetronD. Ondansetron (single doses >16 mg)

and dolasetron

2. Which of the following NK1 receptor antagonists is an inhibitor of CYP2D6?

A. RolapitantB. NetupitantC. FosaprepitantD. Aprepitant

3. When considering formulary decisions, which of the following 5-HT3 inhibitors has the longest half-life and is indicated for both acute and delayed CINV?

A. GranisetronB. OndansetronC. PalonosetronD. Dolasetron

4. CINV can have a major impact on a patient’s qual-ity of life. Several tools are available for clinical assessment of nausea and vomiting in patients. Which of the following tools has 17 items in the questionnaire that may be a barrier to its use?

A. Functional Living Index–Emesis (FLIE)B. Morrow Assessment of Nausea and Emesis

(MANE)C. Rhodes Index for Nausea, Vomiting, and Retching

(INVR)D. MASCC Antiemesis Tool (MAT)

5. WL is a 67-year-old male being treated with cisplatin for lung cancer. Which of the following 4-drug combinations is a recommended regimen for preventing acute CINV for WL?

A. Aprepitant + dexamethasone + palonosetron + olanzapine

B. Aprepitant + metoclopramide + palonosetron + olanzapine

C. Aprepitant + dronabinol + NK1 + olanzapineD. Fosaprepitant + dexamethasone + NK1 + nabi-

lone

6. BR is a 47-year-old female being treated for breast cancer with TAC regimen (docetaxel, doxorubicin, and cyclophosphamide), a protocol with moderate emetogenicity risk. BR had been receiving NEPA and dexamethasone for CINV prevention. During her fourth round of TAC, BR experienced breakthrough CINV. Which of the following agents would be preferred per National Comprehensive Cancer Network guidelines to treat the breakthrough CINV?

A. High-dose metoclopramideB. LorazepamC. OlanzapineD. Haloperidol

7. Which of the following 5-HT3 antagonists is available as a transdermal patch?

A. PalonosetronB. OndansetronC. DolasetronD. Granisetron

8. CINV is one of the most well-known and common adverse events in cancer chemotherapy. Patients often negatively anticipate the symptoms of nausea and vomiting when starting chemotherapy. CINV can negatively affect a patient’s quality of life, including increased healthcare costs. Based on studies cited in this module, overall health care costs can increase for patients with CINV by what factor?

A. A factor of 2B. A factor of 4C. A factor of 6D. A factor of 10

9. Of the following compounds, which is the most likely to be included in the antiemetic formulary for CINV?

A. GingerB. Medical marijuanaC. DronabinolD. Cannabis oil

10. Studies suggest that approximately 40% of clini-cians did not follow antiemetic guidelines regarding CINV prophylaxis. Which of the following is the most appropriate reason for following antiemetic prophylaxis guidelines?

A. Following guidelines may result in significant reductions in the occurrence of CINV and improved outcomes.

B. Following guidelines will eliminate risk of CINV.C. Following guidelines will eliminate risk of mal-

practice.D. Following guidelines will ensure the lowest-cost

antiemetic treatment.

Educational Disclaimer: Continuing professional education (CPE) activities sponsored by Pharmacy Times Continuing EducationTM are offered solely for educational purposes and do not constitute any form of professional advice or referral. Discussions concerning drugs, dosages, and procedures may reflect the clinical experience of the author(s) or they may be derived from the professional literature or other sources and may suggest uses that are investigational in nature and not approved labeling or indications. Participants are encouraged to refer to primary references or full prescribing information resources.

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POSTTEST

DIP Fall Overview7 Live CE Sessions in 1 Day! The role of the pharmacist is evolving! Today, pharmacists are called upon as crucial members of the health care team to routinely discuss safety, efficacy and reimbursement issues with physicians, patients, caregivers and payers.

HAVING CONFIDENCE TO INITIATE THESE DISCUSSIONS IS CRITICAL!

Pharmacy Times Continuing Education™ is offering a 1-day regional meeting for pharmacists to increase their knowledge and confidence in disease topics that are impacting health care today.

Fall Series

N E W B R U N S W I C K , N E W J E R S E Y

October 21, 2017 Hyatt New Brunswick

A N A H E I M , C A L I F O R N I A

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D A L L A S , T E X A S

September 9, 2017 Sheraton Dallas Hotel

C H I C A G O , I L L I N O I S

September 23, 2017Chicago Marriott O’Hare

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C O M P L E T E

C O M P L E T E

Use Code: SEPTEMBERand get 50% off registration fee

Register Here: www.PharmacyTimes.org/dipfall17

Fall 2017 — Preliminary Agenda* Registration/ Breakfast

Welcome

Keynote Address

Session 1: Identifying Opportunities to Improve Vaccination Rates for Adult and Pediatric Populations (0.1 CEU)

Session 2: The Role of the Pharmacist in Pneumococcal Vaccination (0.1 CEU)

Break

Session 3: The Role of the Pharmacist in Managing HIV Treatment (0.1 CEU)

Session 4: Applying Quality to Heart Failure Readmission in Heart Failure (0.1 CEU)

Lunch

Session 5: Improving Cardiovascular Health in Patients with Diabetes: The Pharmacist’s Role in Interpreting and Applying Quality Measures (0.1 CEU)

Session 6: Applying Quality to Post-Surgical Opioid-Induced Constipation (0.1 CEU)

Break

Session 7: Role of the Pharmacist in Adverse Event Management and Prevention with Oral Targeted Anticancer Agents (0.1 CEU)

Adjourn

7:00am

7:30am

7:45am

8:15am

9:15am

10:15am

10:30am

11:30am

12:30pm

1:30pm

2:30pm

3:30pm

3:45pm

4:45pm

*Proposed Timeline: Subject to Change

• Circulation to over 20,000 pharmacy benefit decision makers

• An expedited review process

• Exposure through Web and print publication opportunities

•

OUR JOURNAL BOASTS:

2017 TOPICS:

AJPB® is continually seeking submissions on a variety of topics. Areas of particular interest include utilization management, outcomes research on

Medicare Part D, analysis of drug therapies, cost utility analyses, and more.

www.ajpb.com/call-for-papers/information-for-authors

• Alternative Payment Models

• Biosimilars

• Cost-Sharing Strategies

• Economic Burden of Disease

• e-Prescribing

• Opioid Agonists

• Readmissions

• Specialty Pharmacy

• Value-Based Care

Call for Papers

Indexing in EMBASE/Excerpta Medica and Cumulative Index to Nursing and Allied Health Literature

www.ajpblive.com

© 2017 by Pharmacy & Healthcare Communications, LLC

Volume 9, No. 1 January/February 2017

FROM THE EDI TOR

The Value of Vaccination:

Myth vs Evidence in the

New Administration

In our quest to identify the areas and activities

that show the greatest positive impact and value

in care and outcomes, we must aim to not let

good science and evidence get away from us,

particularly when considering vaccination.

Berger

NAT IONAL PHARMACEU T ICAL COUNCIL

What Are Key Considerations

for Health Reform?

Having the right evidence, using high-value care,

and developing strong incentives to improve pay-

ment and delivery systems are among the ways

we can improve healthcare.

Leonard


®

®


PHARMACY BENEFITS

ORIG INAL RESE ARCH

Modeled Cost Differences Associated

With Use of Levonorgestrel Intrauterine

Devices

This analytic model assessed the per-woman cost differences

between the use of 2 levonorgestrel-releasing intrauterine devices, from

a US payer perspective.

Law, McCoy, Lingohr-Smith, Lin, and Lynen

ORIG INAL RESE ARCH

Patient Characteristics’ Effect on the

Conversion Between Basal Insulins

The characteristics of patients who require increases in their basal insulin

dose were compared with those requiring no increase following

conversion between basal insulin analogues.

Donaldson, Greck, Michalove, and Al-Achi

ORIG INAL RESE ARCH

Cost-Effectiveness of Extended-Release

Carbidopa-Levodopa for Advanced

Parkinson’s Disease

Existing levodopa therapies for Parkinson’s disease often provide

inadequate symptom control after prolonged treatment. This study

assessed the cost-effectiveness of an extended-release carbidopa-

levodopa formulation (IPX066).

Arnold, Layton, Rustay, and ChenVisit ajpb.com

www.ajpblive.com© 2017 by Clinical Care Targeted Communications Group, LLC | www.ajpb.com

Volume 9, No. 2 March/April 2017

FROM THE EDI TORFollow the Numbers: A Focus on Anti-Inflammatory Medications

In addition to having a major impact on patient health outcomes, medications can have significant cost implications for all stakeholders; insurers and employers need to work with their pharmacy benefit managers to ensure that the right patients are getting the right medications at the right time.Berger

NAT IONAL PHARMACEU T ICAL COUNCILHow Can We Address Barriers to Accessing Needed Care?Adherence and access to higher-value care can make a big difference in reducing costs for patients and our healthcare system; however, the financial burden of high-deductible health plans and out-of-pocket costs must also be considered.Dubois


®

®

The American Journal ofPHARMACY BENEFITS

ORIG INAL RESE ARCHLarge-Scale, Community-Based Trial of a Personalized Drug-Related Problem Rectification System

A controlled trial of a system for rectifying and preventing drug-related problems was conducted to evaluate improvement in the efficiency of resource utilization.Kahan, Waitman, Berkovitch, Yosselson Superstine, Glazer, Weizman, and Shiloh

ORIG INAL RESE ARCHTelephone-Based Cardiovascular Medication Therapy Management in Medicare Part D Enrollees With Diabetes A telephonic pharmacist-delivered medication therapy management intervention is an effective method for increasing the use of guideline-recommended cardiovascular therapies in high-risk Medicare patients with diabetes.

Caplan, Guy, Chang, and Boesen

ORIG INAL RESE ARCHGeneric Use Under Changing Co-Payments: Implications for Those With Multiple Chronic ConditionsPatients with multiple chronic conditions are less likely to use generic drugs, even when facing lower co-payments.

Buttorff

• Circulation to over 20,000 pharmacy benefit decision makers

• An expedited review process

• Exposure through Web and print publication opportunities

•

OUR JOURNAL BOASTS:

2017 TOPICS:

AJPB® is continually seeking submissions on a variety of topics. Areas of particular interest include utilization management, outcomes research on

Medicare Part D, analysis of drug therapies, cost utility analyses, and more.

www.ajpb.com/call-for-papers/information-for-authors

• Alternative Payment Models

• Biosimilars

• Cost-Sharing Strategies

• Economic Burden of Disease

• e-Prescribing

• Opioid Agonists

• Readmissions

• Specialty Pharmacy

• Value-Based Care

Call for Papers

Indexing in EMBASE/Excerpta Medica and Cumulative Index to Nursing and Allied Health Literature

volume 9, no. 5 september/october 2017 - amazon web … › _media › _pdf ›...

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