Inpharma 1500 - 13 Aug 2005

Etanercept the clear winner vs infliximab in AS, PA– Kimberley Salmon –

Ankylosing spondylitis (AS) is arthritis which involves the spine, generating ongoing swelling and irritation of thevertebrae, which causes pain and stiffness in the back, and may lead to fusion of the vertebrae. Psoriatic arthritis(PA) is a chronic, debilitating, immune-mediated inflammatory disorder characterised by symptoms of skin andjoint disease; as many as 34% of patients with psoriasis will go on to develop arthritis symptoms along with theirskin symptoms. The tumour necrosis factor (TNF) inhibitors etanercept [Enbrel] and infliximab [Remicade] arelaunched to treat AS and PA, and have shown in studies to date to provide rapid and durable improvements insymptoms for patients with these disorders. Analyses of the costs associated with such therapies were conductedby investigators presenting their research at the Annual European Congress of Rheumatology (EULAR) [Vienna,Austria; June 2005].

A multinational group of researchers sought to these new biologics are associated with significantlymonitor the long-term safety and efficacy of etanercept higher costs than traditional therapies, investigatorsin patients with AS, and to assess the drug’s efficacy in from the US designed a study to assess their costpatients switched from placebo.1 effectiveness for treating patients with AS.2

The researchers’ open-label extension study followed Best for AS from US MCO perspectivepatients from a prior 24-week double-blind randomised The investigators developed an economic model withcontrolled trial (RCT) in which they had received either a one-year time horizon, using data obtained fromSC etanercept 25mg (n = 138) or placebo (139).* In the published literature and expert opinion, to determineextension study, all patients received SC the cost effectiveness of etanercept and infliximab frometanercept 25mg twice weekly for ≤ 168 weeks; 257 a US managed care organisation’s (MCO) perspective.**patients entered the extension study and 200 completed The model assumed equal efficacy rates for theit. Effectiveness of etanercept was defined (in both the medications, "supporting a cost-minimization analysis toRCT and the extension study) as a 20% improvement in quantify the per patient cost and budget impact on anAssessment in Ankylosing Spondylitis (ASAS) Response MCO", note the investigators. The total direct medicalCriteria and multiple secondary outcomes including costs associated with the administration of etanerceptspine mobility; baseline values from the RCT served as 50mg weekly and infliximab 5 mg/kg at weeks 0, 2, 6baseline assessments. and every 6 weeks thereafter were assessed for a"Sustained durability of response" hypothetical patient with AS weighing 74kg. All drug

Patients who continued etanercept treatment from acquisition costs were based on US Average Wholesalethe RCT to the open-label extension study showed Prices (AWP), and all administration costs on US"sustained durability of response" after 72 weeks of Medicare 2004 reimbursement rates. The investigatorstreatment, say the researchers. Indeed, of the 95 note that only drug and administration costs werepatients who had previously received ≤ 24 weeks of included, and that adverse event costs were excluded.etanercept treatment in the RCT, 74% achieved a 20% The model showed that the 24-week ASAS20improvement on the ASAS (ASAS20), 52% achieved the response rates were similar, at 0.57 versus 0.22 forimprovement criteria of the ASAS5/6 and 60% for the etanercept versus placebo and 0.60 versus 0.18 forASAS40 criteria by the end of 72 weeks of open-label infliximab versus placebo. However, costs associatedtreatment with etanercept. In addition, patients who with infliximab would be significantly greater than thosereceived placebo in the RCT and switched to etanercept associated with etanercept. Indeed, total one-year per-in the open-label study showed "rapid improvement" patient costs would be $US25 543 for infliximabfrom baseline, with week 24 values similar to those compared with $US14 636 for etanercept. Medicationobserved for etanercept recipients in the RCT, note the costs accounted for > 90% of the total costs, with drugresearchers. Mean Bath Ankylosing Spondylitis administration and physician visits and laboratory testsFunctional Index (BASFI) and Bath Ankylosing accounting for the remainder. Cost-effectivenessSpondylitis Disease Activity Index (BASDAI) scores also analysis indicated that infliximab would cost more thanimproved from baseline in both groups. $US150 000 per additional ASAS20 responder,

Moreover, among patients with impaired spinal compared with etanercept.mobility at baseline, all mean and median measures of The investigators estimated the budget impact for aspinal mobility improved with etanercept treatment. The US MCO by assuming the following:majority of adverse events associated with etanercept • that 35% of AS patients in the plan that arewere of "mild or moderate" intensity, comment the candidates for either infliximab or etanerceptresearchers, and there were no deaths, opportunistic therapy would receive such therapy for 6 monthsinfections, diagnosable cases of multiple sclerosis, • only patients responding to therapy (approximatelyincreased incidence of pneumonia or drug-induced 60% of patients for both agents) would continue tolupus reported. The researchers conclude that SC receive treatment in the first yearetanercept is "well tolerated" and "improves signs and • in years 2 and 3, 50% of responders would continuesymptoms of AS, which is maintained for up to and remain on therapy.two years". Under these assumptions, the MCO budget impact

The comparative efficacy of etanercept and infliximab over 3 years was estimated at just over $US13.6 millionin AS is not known, as no head-to-head clinical trials for etanercept and just over $US22.6 million forhave been carried out. However, as both have been infliximab.recently approved for treating AS, the costs and effects Sensitivity analysis showed the model to be mostof the therapies are of interest to healthcare payers. As sensitive to the infliximab dose and infusion frequency.

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Etanercept the clear winner vs infliximab in AS, PA – continuedHowever, multi-way sensitivity analyses that varied the events were assumed to be equal in both treatment armsinfliximab does, infusion frequency and duration and were therefore not included in the analysis."simultaneously indicated that most infliximab regimens It was estimated that the total costs of therapy wouldwould be more costly than etanercept", the investigators be significantly higher with infliximab versus etanerceptnote. ($US26 369 vs $US18 692 per patient). Moreover,

Etanercept and infliximab are both currently approved infliximab would have an additional cost of $US255 900in the EU to treat psoriatic arthritis (PA), while per ACR20** responder relative to etanercept, makingetanercept is the only approved biologic for this etanercept the economically preferred option, say theindication in the US. The comparative cost effectiveness researchers.of etanercept and infliximab in psoriatic arthritis (PA) Sensitivity analysis proved the results to be relativelywas assessed by researchers from the US.3 robust, with the cost of drug acquisition having the

greatest influence.Economically superior in PA* The research was funded by Immunex Corporation, a subsidiary ofThey performed their cost-effectiveness analysis fromAmgen Inc., and by Wyeth Research. Some of the researchers werethe perspective of a US MCO, comparing SC etanerceptaffiliated with Amgen Inc.25mg twice weekly with IV infliximab 5 mg/kg** improvement from baseline of ≥ 20% in American College ofadministered at weeks 0, 2 and 6 and then every Rheumatology (ACR) score

8 weeks thereafter among patients with PA.* A one-year1. Davis JC, et al. Sustained efficacy of etanercept in ankylosing spondylitis for uptime horizon was adopted, and a mean patient weight of to 2 years. Annals of the Rheumatic Diseases 64 (Suppl. III): 336 (plus poster)

90kg was assumed. All patients completed a full year of abstr.FRI0262, Jul 2005.2. Duff SB, et al. The economic impact of etanercept and infliximab treatment intherapy, regardless of their response. Efficacy rates for

ankylosing spondylitis. Annals of the Rheumatic Diseases 64 (Suppl. III): 400the drugs were obtained from two phase III clinical trials, (plus poster) abstr.FRI0474, Jul 2005.3. Yu EB, et al. A cost-efficacy analsysis of etanercept and infliximab in themedication costs were based on US Average Wholesale

treatment of psoriatic arthritis. Annals of the Rheumatic Diseases 64 (Suppl. III):Prices and administration rates on 2004 US Medicare400 (plus poster) abstr.FRI0473, Jul 2005.

reimbursement rates. Only costs associated with 800999404

medication and administration were included; thoseassociated with adverse events were excluded. Adverse

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