Biologics More Expensive than Triple Therapy for Early Aggressive RA

San Diego—For patients with early aggressive rheumatoid arthritis (RA), initial treatment with triple disease-modifying anti-rheumatic drug (DMARD) therapy is more cost-effective long-term than initial treatment with either an immediate or step-up strategy with biologic therapy (ie, etanercept) plus methotrexate.

This is the conclusion of a study presented at the ACR/ARHP meeting in which investigators used data from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) trial and the National Data Bank for Rheumatic Diseases (NDB) to evaluate the long-term cost-effectiveness of treatment for patients with early aggressive RA.

The TEAR trial was a 2-year, double-blind, randomized trial that compared the efficacy of 4 treatment strategies for early aggressive RA. The treatment strategies included immediate triple DMARD therapy (methotrexate plus sufasalazine plus hydroxychloroquine) or immediate combination biologic therapy (etanercept plus methotrexate), or step-up strategies in which patients with persistent disease switched from methotrexate monotherapy to triple DMARD therapy or methotrexate plus etanercept after 6 months. The TEAR trial found that initial combination therapy did not confer superior clinical or radiographic outcomes compared to step-up therapy. The combination of etanercept plus methotrexate was marginally better radiographically than triple DMARD therapy, and triple DMARD therapy was marginally better clinically.

To compare the cost-effectiveness of these treatment strategies, investigators used a Markov model to estimate the quality-adjusted life years (QALYs) and costs associated with each treatment strategy. The Markov model extended the 2-year TEAR trial outcomes to the lifetime horizon using parameters from the longitudinal NDB data. These parameters included therapy discontinuation rates, Health Assessment Questionnaire (HAQ) transitions, and Disease Activity Scores in 28 joints (DAS28)-HAQ-QUALY mapping. The model also included direct and indirect cost estimates from published literature, as well as 3% annual discounting of costs and effectiveness. For example, the model included the annual costs of triple DMARD therapy ($791, range of $500-$1200) and etanercept ($24,446, range of $12,000-$26,000) based on February 2013 estimates.

The study found that both strategies using etanercept (either as immediate combination with methotrexate or in a step-up regimen) were more costly than either strategy using triple DMARD therapy. Although the lifetime benefits of all 4 strategies were comparable (ie, 0.06 QALY scores), the 2 strategies that included etanercept were almost twice as expensive as the triple DMARD therapy strategies primarily, due to the higher cost of etanercept.

Although immediate combination etanercept plus methotrexate was more effective than immediate triple DMARD therapy, lead investigator Kaleb Michaud, PhD, Assistant Professor, University of Nebraska Medical Center, who presented the results during a scientific session and press conference at the ACR/ARHP meeting, emphasized that the incremental cost-effectiveness ratio of immediate combination etanercept to immediate triple DMARD therapy was $837,100/QALY. Dr. Michaud emphasized that this difference in the incremental cost-effectiveness ratio may be too high for many healthcare settings to find acceptable.

He advises against changing practice from the current American College of Rheumatology treatment guidelines for early RA that indicate adding concomitant anti-tumor necrosis factor biologic or another nonbiologic DMARD to methotrexate in patients who fail initial methotrexate, depending on the severity of the prognosis. However, Dr. Michaud emphasized that the results of the study suggest that triple DMARD therapy be considered a viable alternative to a biologic for patients where costs may be an impediment to care.