1
APhA Immunization Update from the June 2011 ACIP Meeting
Stephan L. Foster, Pharm.D.CAPT (Ret) U.S.P.H.S.
Professor and Vice ChairUniversity of Tennessee College of Pharmacy
Liaison MemberCDC Advisory Committee on Immunization Practices (ACIP)
AccreditationThe American Pharmacists Association is accredited by theAccreditation Council for Pharmacy Education as a provider of
continuing pharmacy education. This activity, APHA Immunization Update from the June 2011 ACIP Meeting, is approved for 1.0 hours of continuing pharmacy education credit (0.10 CEUs). The ACPE Universal Activity Number assigned by the accredited provider is: 202-000-11-106-L04-Passigned by the accredited provider is: 202-000-11-106-L04-P.To obtain continuing pharmacy education credit for this activity, participants will be required to actively participate in the entire webinar and complete an online evaluation and CPE recording form located at www.pharmacist.com/education by July 29, 2011.Initial Release Date: June 29, 2011Target Audience: PharmacistsACPE Activity Type: Knowledge-BasedLearning Level: 1Free CPE credit is brought to you by your APhA membership. Non-members will be assessed a $25 CPE activity fee for this webinar.
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
2
Learning ObjectivesIdentify changes to vaccine recommendations necessary for compliance with standards of practiceApply recent changes to guidelines to their vaccination programEvaluate information on new or future vaccines for potential use in their practice
DisclosuresStephan Foster, Pharm.D., serves on the Merck speakers bureau and is on an Advisory Board of both Sanofi Pasteur and GSK
APhA staff member, Mitchel Rothholz, R.Ph., declares that his spouse is an employee of Merck.
All other APhA editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria.
DisclaimerThis contains data presented at the ACIP meetingSome of this data is unpublishedIf there is a slide without a reference, then it contains
h d tsuch dataDo not quote this specific data until it is publishedACIP meeting minutes will be on the ACIP website in the near future, along with the meeting slides
www.cdc.gov/vaccines/recs/acip/default.htm
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
3
Advisory Committee on Immunization Practices
Members15 Experts in the field of Immunization
Voting MembersEx-officio Members (9)Liaison Members (33)
MissionProvide advice and Guidance to CDCDevelop written recommendationsReduce the incidence of vaccine-preventable disease
Meets 3 times a year
More often in subcommittees
7
Advisory Committee On Advisory Committee On Immunization PracticesImmunization Practices
Advisory Committee On Immunization Practices
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
4
Herpes ZosterFDA license for adults 50-59 years (March 2011)
Herpes ZosterACIP Recommendation October 2006 for all > 60 years old
Contraindication of immunosuppressionNot recommended for persons who received varicellaNot recommended for persons who received varicella vaccine
Not intended to treat active diseaseRecommended regardless of previous zoster historyStorage frozen
Refrigerator stable version requires 50% more antigen
Disease Considerations Serious disease with pain and sufferingHigh direct and indirect costsWill never eliminate the diseaseBurden of disease increases sharply after age 50
Hospitalizations, death, pain, severityWorsens at older ages
Except work-loss costs
Only a few vaccines used where risk of disease increases with age
Influenza and pneumococcal
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
5
Olmstead County, MN 1998-2001
Yawn BP, et al. Mayo Clin Proc 2007;82:1341-9
Shingles Prevention StudiesOxman, et al. NEJM 2005;352(22):2271-84
38,000 patientsFollowed for 3.1 years51% reduction in cases
Effectiveness reduced with ageLess likely to progress to PHN is you get shinglesBiggest effect seen in those >70 years
Tseng, et al. JAMA 2011;305(2):160-675,000 vaccinees vs. 227,300 non-vaccineesEffectiveness 55%
Effectiveness stable with age
ZEST Trial 50-59 year oldsZostavax Efficacy and Safety Trial
2007-201122,439 patients
C f Z tCases of Zoster30/11211 in vaccine group99/11228 in placebo groupEfficacy 69.8%
Generally well toleratedMore ADEs in vaccine groups
Mostly local reactions and headacheSimilar serious ADEs to placebo
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
6
HZV Duration of Protection
Schmader, IDSA 2008
PersistenceOnly short term studies
3-4 yearsLonger studies ongoingNo good or reliable immunological markers availableVaccine effectiveness wanes over timeCost effectiveness
Lower at younger age since disease incidence is lowerLower in older age due to more deaths
Supply IssuesRecurring shortages since Zostavax® licensed
Also affected MMRVNo effect on Varicella (Varivax ®)
Li i l d tiLive vaccine-complex productionVariability in bulk vaccine yields
Back-orders starting to get filledDelay still through first half of 2011Expect 2 million doses for rest of 2011Expect to meet demand for >60 year-olds in 2012
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
7
ACIPOnly about 10% of >60 years are vaccinatedLimited supplies may be diverted to younger age
C ld lt i i i t diCould result in increase in zoster diseaseACIP has never recommended expansion of vaccine usage during shortage
The working group does not propose a revision of existing recommendations regarding zoster vaccine at this time
VaricellaChanged to 2 dose recommendation in 2006
Outbreaks in highly vaccinated schools1 dose – incomplete protection
Vaccination rates 85-100%Vaccination rates 85 100%A few states do not require at kindergartenRates 63-79%
2 dose vaccination safety demonstratedVaricella Active Surveillance Project
Significant decline in disease since 2006Most cases seen in unvaccinated or only having 1 dose
Meningococcal VaccineBooster dose recommended January 2011Menveo®(Novartis) indicated for 2-10 year-oldsL t ACIP t t t 2005Last ACIP statement 2005
Under revisionMenactra®(sanofi-pasteur) licensed in infants for 2 dose series in 9 – 23 months of age (3 months a part)
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
8
Number of cases of meningococcal disease causing meningitis, pneumonia, or bacteremia, by serogroup, Active Bacterial Core surveillance sites (excluding cases from Oregon), 1998–
2007.
Cohn A C et al. Clin Infect Dis. 2010;50:184-191
Meningococcal DiseaseU.S. Serotypes 2006-2008
B – 29%C – 29%Y 33%Y – 33%W 135 – 8%
Deaths – Case Fatality Rates (CFR)W 135 – 16.3%C – 14.7%Y – 12%
Trends in meningococcal disease incidence by race, 1998–2007.
Cohn A C et al. Clin Infect Dis. 2010;50:184-191
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
9
Menactra® (sanofi-pasteur)Safety Studies
Adverse events vs. placeboAdverse events in combinationsL l ADE d t iLocal ADE and systemic
Efficacy StudiesPhase III studiesIncluded combination with MMRV, PCV7
PCV7 serotype GMCs lower Protective levels demonstrated (titers > 1:8)
Menactra® (sanofi-pasteur)FDA Approved April 2011
2 dose series9 – 23 months with booster 3 months later
Demonstrated immune response asDemonstrated immune response as protectiveSafe alone and in combinations with MMWR and PCV7
No data with PCV13Duration of effect appears to be about 3 years
ACIPAnticipates 2 more vaccines within next year
2,4,6,12-15 month schedulesWill wait to consider adding to routine schedule
R d tiRecommendationApproved for high risk
Complement deficiency, outbreak exposures, travel to endemic areasDecided to wait for functional or anatomical asplenia
Pneumococcal more important
Approved for VFC
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
10
Epidemics in AfricaEpidemics occur in dry seasonOccur every 5-12 years80-85% Type A1988-1997
704,000 cases>100,000 deaths
1998-2002224,000 new cases
Meningococcal VaccineCampaign in Sub-Saharan Africa began in 1996 (Meningitis Vaccine Project)
Serotype A Conjugate Vaccine produced in India$0.40 per dosep
MenAfriVac licensed in 2009Serotype A vaccineGiven to ages 2-29 years (>100% coverage)
Significant decline in meningococcal diseaseMay eliminate “Meningitis Belt” within 10 years
Prevent 123,000 deathsPrevent disability to 287,000
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
11
http://www.meningvax.org/
Measles UpdateJan 1– June 17, 2011 United States
156 cases measles (largest since 1996) 12 outbreaks3-21 cases per outbreakp
89% US residents85% unvaccinated or unknown status34% hospitalized87% import associated
From all over globeMost from Europe
Outbreaks in France, Spain, and BelgiumNext largest from India
PertussisRecommendation in previous ACIP meetings
All adults need 1 dose TdapExcluded pregnancy at that time
Gi Td if d d (Td t t i di t d)Give Td if needed (Tdap not contraindicated)Give TDAP post partumCocooning of family members
Usually inactive vaccines safe in pregnancyVaccines indicated in pregnancy
Influenza and tetanus toxoidNo evidence of toxicity
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
12
Tdap in PregnancySafety
VAERS – no signalsTd and TT used for years
N id f t t i itNo evidence of teratogenicitySimilar evidence seen in post marketing surveillance by sanofi-pasteur with Adacel®
Cost EffectivenessTdap in pregnancy more cost effective than cocooning
Cost per QALY calculations18 variables used in calculations
Cost-Effectiveness ModelsQuality-Adjusted Life Year (QALY)
1 year in perfect health = 1 QALYDeath = 0 QALY1 year in less than perfect health between 0 and 1y p
Cost per QALY(Vaccine + admin cost)-(cost of illness averted by vaccination)
Number of QALYs gained by vaccination
Threshold for cost effectivessNo concensusUS: $50,000-$100,000 often citedWHO: < 3 times per capita GDP (US per-capita GDP=$50,000)
Cost per Outcome GainedChildhood
DTAP, Hib, MMR, Polio, Varicella <$0 per QALYCost saving
Influenza (LAIV) ~ $10 000Influenza (LAIV) ~ $10,000Rotavirus ~ $135,000-$225,000
AdolescentsMeningococcal
11-17 y/o ~$105,00011 y/o (routine) ~$140,000
Influenza Healthy ~$140,000High-risk ~$10,000
Tdap ~$25,000
http://www.cdc.gov/vaccines/recs/acip/slides-oct10.htm#evidence
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
13
Tdap in PregnancyImmune Interference
Transplacental antibody transmission to infant? Cause blunting of infant response to vaccinationShift i k f di f t ld i f tShifts risks of disease from younger to older infants
Reduce disease and death in <4 months of age (period of most infant deathsPossibly shifts higher risk to older infants
Tdap in PregnancyCanadian study underway
Double blinded, randomized control (Td or Tdap)Passive protection
T l t l b t ilkTransplacental or breast milkImmunization of infant with DTaPStill blinded
Elevated Ab levels at birth and 2 months in 1 groupLower antibody levels in same group at 1 month after 3rd
DTaPComparable antibody levels at 4-6 monthBoth groups increasing levels at 6-7 months
Tdap in PregnancyCocooning
Limited dataInitial evidence of effectivenessNo success at national level
Poor uptake by fathers and family membersPoor uptake by fathers and family membersConclusion
Continue to recommendInsufficient national strategy
VaccinationMost experts consider safeProgrammatic cost are equal
Tdap recommended postpartum
Protects both mother and infant
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
14
ACIP VoteRecommend Tdap vaccination preferably during the late second or third trimester of pregnancy (after 20 weeks) if they have never received a previous Tdap If it is notreceived a previous Tdap. If it is not administered during pregnancy, the Tdap should be administered immediately postpartum. Cocooning of family members is still encouraged.
Vaccine SupplyHepatitis B Vaccine
Merck – no supply except dialysis vaccineGSK OK
Hepatitis AHepatitis AMerck – Available in 2012GSK OK
MMRV – No timing details availableZoster – Previously covered (2-3 month wait)Cervarix (HPV)
Vials discontinued (Syringes available)
http://www.cdc.gov/vaccines/vac-gen/shortages/default.htm
Estimated Percentage of Cancers Associated with HPV
CANCER ANY HPV % HPV 16/18 %EstimatedAnnually
2004-2006
Cervical 96 76 9000
Vaginal 64 56 400
Vulvar 51 44 1,350
Anal 93 872,590 (F)1,410 (M)
Penile 36 31 310
Oropharyngeal 63 601,380 (F)5,360 (M)
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
15
National, State, and Local Area Vaccination Coverage among Adolescent Females Aged 13-17 Years – U.S.
35404550
05
1015202530
2007 2008 2009
> 1 Dose3 doses
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5932a3.htmhttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a2.htm
HPV Duration of ProtectionNordic Study – 7 years out
Original Phase IIICancer RegistriesV i Eff ti (VE)Vaccine Effectiveness (VE)
HPV 16/18 CIN 2 or worse = 100%HPV other types = 3 cases/1217
Serological Titers (Anti-HPV - % seropositive)Compared at 7 and 72 monthsTiters similar for types 6, 11, and 16Lower in type 18 but no breakthrough cases
Follow up continues
Human Papillomavirus VaccinesUse in males
Permissive recommendation in Oct 2009New FDA approval for anal cancerA i t d ith h lAssociated with oropharyngeal cancerVaccine Efficacy Males
89% Genital Wart75% Anal Intraepithelial Neoplasia 2/3
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
16
Vaccination of Males with HPV Vaccine
Cost Effectiveness - Published studies$24,000 – $62,000 (Cost effective if vaccination of girls is low)Male vaccination less cost-effective as female coverage increasesAt current female coverage, male vaccination could be cost-effectiveCost of vaccine plays most important part of calculation
October ACIP MeetingConsider policy change to include routine for malesStronger recommendation for MSMWill Catch-up schedule be recommended?
Oropharyngeal Cancer (OP)HPV 16 causes cancer on OP
Distinctly different from HPV – negative tumors
Oral HPV 16 rare in healthy personsOP cancer increasing in U SOP cancer increasing in U.S.Risk Factors for oral HPV infection
Age and GenderSexual behavior
Number of partnersKissing and other oral sexual behaviorsTobacco useHIV infection
Evidence for HPV vaccine protection is lacking
Vaccines and Febrile Seizures2-5% of children aged 6-60 monthsMentioned in most PI of vaccinesReported most commonly with:
DTwP (no increase with DTaP)MMR
2010 Australia InfluenzaSlight increase with TIV and PCV13 given together
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
17
Febrile SeizuresFever is common and can lead to febrile seizuresSimple febrile seizure
97%Last less than 15 minutes No recurrence
Complex febrile seizuresFocalLast longer than 15 minutesRecurrent within 24 hours
Risk of epilepsy same as general populationSlight increase (2.4%)
If multiple, first before age 12 months, family historyGood prognosis but frightening to parentsExpensive to work-up
Vaccines and Febrile SeizuresVaccine Safety Data Link (continued)
Looked at PCV, PCV + TIV, TIV aloneOnly increase seen in TIV + PCV13O l i ifi t i hild 12 23 th ldOnly significant in children 12-23 month old group1 case/2375 vaccinees (42/100,000)
Feb ACIP - 1 case/1,640 doses (61/100,000 doses)May have received other vaccinesOnly increase in 2010-2011 season
Risk of DiseaseInfluenza
Age 12-23 monthsHospitalizations 3-11/10,000
Seizures reported in 8%Seizures reported in 8%0.77 deaths/100,000
Pediatric Deaths282 in 2009-10106 in 2010-11
Pneumococcal Children <5 years
42,000 Hospitalizations1 million episodes of illness
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
18
Febrile Seizure DiscussionsRisk 1/1641
One every 7 years in pediatric clinicOne every 28 years in family medicine clinic
HHowever…..Risk with MMRV was 1/2000Recommendation not to give on first dose
Again seizures, while benign, are frighteningRecommend education of patients, but not to change ACIP recommendation
Hepatitis BCases in 2009-2010 Behavioral Risk Factor Surveillance System Survey (NYC)
Acute hepatitis B – 331 casesThose with diabetes 49Those with diabetes – 49
Total diabetics17.2 million total8.4 million aged 20-59
Estimates of protection with vaccineAge 29-59 years
5071 infections prevented304 chronic cases prevented
Hepatitis B VaccinationCost effectiveness
More diabetics with hepatitis B than non-diabeticsVaccination efficacy decreases with ageCost
A 20 59 $58 762 QALYAge 20-59 = $58,762 per QALYAll ages = $159,000
Options for ACIP vote in OctoberAll diabetics at time of diagnosisAll diabetics <60 years of age
Consideration of risk factors
ConsiderationsEfficacy at what age groupCatch-up
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
19
13-Valent Pneumococcal Conjugate Vaccine
PCV 13 anticipated FDA approval in Adults >50 years (October 2011)Public Health and economic impact
P t d b PfiPresented by PfizerBased assumptions on limited dataExtrapolated to all adultsModel with minimal clinical dataModel with many assumptions
Pneumococcal Disease and VaccinationEpidemiology
Large herd effect from PVC7Expectations from PCV13 unknown
Pneumococcal disease high among adults >50 yearsVariable efficacy data for PCV 23
Considerations for PVC13Considerations for PVC13Published immunogenicity studies non-inferior for select serotypes in vaccineEfficacy in HIV adult adults
74% for vaccine serotypes vs 25% for all cause pneumoniasApproximately 20-30% disease in adults from Non-PVC13 serotypes
Cost Effectiveness – Possibly!Many assumptions
PVC13 effectiveness against noninvasive pneumoniaPPSV23 effectiveness against IPDHerd Immunity of PCV13
Working group waiting for more data
InfluenzaEpidemiology2010-2011 vaccine coverage2010-2011 vaccine effectivenessFluzone High doseIntradermal VaccineInfluenza and egg allergies
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
20
2010-3
2010-3
Pediatric Deaths 2010-11106 Total (110 latest)
27 (26%) A(H1N1)18 (17%) A(H3N2)20 (19%) A k t20 (19%) A unknown type40 (38%) B
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
21
InfluenzaActivity currently lowStrains matched vaccine well last yearVaccine effectiveness estimated at ~60%No evidence of antigenic driftTotal Vaccine Distributed – 163 million
http://www.cdc.gov/mmwr/PDF/wk/mm6022.pdf
Seasonal Vaccination Coverage 2010-2011
Group 2009-2010 (%) 2010-2011 (%)Overall (>6 Months) 41.3 42.8Children 6 Months-17 years 42.3 49.0Persons > 18 years 40.5 40.9
18-49 yrs 30.3 30.250-64 years 44.8 45.6> 65 years 68.9 68.6
Pregnant Women 32-51 44-49Healthcare Providers 62 56-65
http://www.cdc.gov/mmwr/PDF/wk/mm6022.pdf
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
22
Fluzone® High-DoseLicensed December 2009Available 2010-2011 Season10% of persons >65 years immunizedHigher rates of nausea, vomiting and diarrhea than regular Fluzone®
Clinical trial to begin in Fall 2011
Intradermal Influenza Vaccine
Intradermal Influenza VaccineSkin plays major role in immune functionRich in immune cellsGreat blood vasculature and lymphatic
tsystemDendritic cells contibute to immune memory and long-lasting B cell response
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
23
Micro-Injection system
ID Administration
Intradermal Influenza Vaccination90% smaller needle (1.5mm)27 mcg antigen (45 mcg in regular dose)/ 0.1mlI di t d 18 64Indicated 18-64 yearsGood immune responseMore injection site reactionsHigh level of provider and patient acceptance
Copyright (C) 2011, American Pharmacists Association. All rights reserved.
24
Influenza Vaccine and Egg AllergyReview of data
Risk of allergy much lower than risk of influenzaNo reported serious reactions to 2700 egg allergic patientsSkin testing not predictive of reaction
ACIP voteNot a contraindication but a precautionIf problem with eggs is hive
Receive TIV and not LAIVLow ovalbumin product (all 2011 products are)Observe for 30 minutes
Persons with risk for more serious reactionsReferred for further work-up
Summary and ConclusionsNext ACIP Meeting October 25-26, 2011 in Atlanta, GA
Next Webinar scheduled for November 9, 2011
If you have questions please contact:Stephan L. Foster, Pharm.D.E-mail: [email protected]
Questions/comments
Copyright (C) 2011, American Pharmacists Association. All rights reserved.