[2009] [THU0521] COST EFFECTIVENESS OF ADALIMUMAB IN COMBINATION WITH METHOTREXATE VERSUS METHOTREXATE MONOTHERAPY BASED ON RESULTS FROM PREMIER USING DATA ON RADIOGRAPHIC PROGRESSION

B.A. van Hout¹, S. Ray², S. Thurston³, C. Bojke³, M.F. Botteman⁴, M.A. Cifaldi^{2 1}University Medical Centre Utrecht, Utrecht, Netherlands; ²Global Health Economics and Outcomes Research, Abbott, Abbott Park, United States; ³Pharmerit International, York, United Kingdom; ⁴Pharmerit North America LLC, Bethesda, United States

Background: The PREMIER study demonstrated that combination therapy with adalimumab (ADA) and methotrexate (MTX) was superior to MTX monotherapy in patients with early rheumatoid arthritis (RA) in terms of improved American College of Rheumatology (ACR) response and less radiographic progression of joint damage.¹
Objectives: To evaluate the cost effectiveness of combination therapy with ADA and MTX versus MTX monotherapy in patients with early RA, based on differences in irreversible joint damage as indicated by radiographic progression.
Methods: A patient simulation model was built with disease activity as an underlying unobserved variable. Immediate effects of disease activity were assumed to be captured by ACR response variables. Irreversible effects of joint damage were assumed to be captured by radiographic measures of erosion and joint narrowing (total Sharp score [TSS]). ACR variables and TSS were linked to the Health Assessment Questionnaire (HAQ), which in turn was linked to estimates of costs, quality of life, and survival. Data were obtained from PREMIER, a Phase III study of ADA in early RA. Long-term irreversible impairment from joint damage was estimated based on the HAQ and TSS,² and mortality was estimated based on the HAQ.³ Patients were assumed to start treatment with either combination therapy or MTX monotherapy. Patients with <50% response after 6 months were assumed to switch to a non-MTX disease-modifying antirheumatic drug (DMARD). Efficacy of DMARDs was estimated as described.⁴ Patients were assumed to discontinue DMARD therapy after 4 different failures. Patients who after 6 months had <50% response to therapy for more than 4 consecutive weeks were assumed to withdraw from therapy. Costs (in British £) and effects were calculated over 30 years and were discounted at 3.5% per year. Univariate and multivariate sensitivity analyses were applied.
Results: Combination therapy with ADA+MTX was estimated to yield more quality-adjusted life-years (QALYs) than MTX alone per patient initiating therapy. With HAQ responses decreasing on average by 0.75 points per year, the lifetime gain with ADA+MTX was estimated at 2.83 QALYs. Lifetime treatment costs were estimated at £197,391 when starting on combination therapy and at £164,481 when starting on MTX monotherapy, a difference of £32,910. When indirect costs (work productivity) were considered, the cost difference was reduced by £24,842 to £8,068. Cost effectiveness of ADA+MTX versus MTX monotherapy improved from £12,042/QALY to £2,856/QALY when indirect costs were included. Removing the difference between ADA+MTX versus MTX in preventing radiographic progression increased costs to £44,773/QALY.
Conclusion: Early prevention of radiographic progression and cost savings due to improved work productivity predicted a favorable balance between costs and effects with combination ADA+MTX therapy.
References:

1. Breedveld FC, et al. Arthritis Rheum. 2006;54:26-37;
2. Aletaha D, et al. Arthritis Rheum. 2006;54:2784-92;
3. Sokka T, et al. Ann Rheum Dis. 2004;63:494-7;
4. Geborek P, et al. Ann Rheum Dis. 2002;61:793-8.