[Contribution of leflunomide to the cost effectiveness of sequential DMARD therapy of rheumatoid arthritis in Germany]. / Wirtschaftlichkeit von Leflunomid bei sequentieller Basistherapie der rheumatoiden Arthritis in Deutschland.

Since November 1999, leflunomide (LEF), an innovative disease-modifying antirheumatic drug (DMARD), is available in Germany for treatment of rheumatoid arthritis (RA). LEF slows radiographic disease progression and improves functional capacity as well as healthrelated quality of life of RA patients. Resources for health care of the patients are limited in Germany as in all other countries. The purpose of the analysis therefore was to compare the cost effectiveness of the following alternatives: LEF in sequential monotherapy with other DMARDs versus sequential monotherapy of other DMARDs. The target variables of this cost-effectiveness comparison were additional direct costs per ACR20-response year (ACR20RY) gained and per quality-adjusted life year (QALY) gained, respectively, each after three years of treatment. The cost-effectiveness comparison was carried out using a modeling study after secondary analysis of relevant data. Oral methotrexate (MTX), sulphasalazine (SSZ), antimalarials (CQ/HCQ), intramuscular gold (IMG), and azathioprine (AZA) were selected as "other" DMARDs representing the current status of sequential monotherapy. Based on health care regulation in Germany-Guidelines on the Prescription of Drugs amended by the Federal Commission of Medical Practitioners and Health Insurance Funds on 10 December 1999-LEF was exclusively considered second within a DMARD sequence. Direct costs were given by outpatient and inpatient treatment, long-term care, and rehabilitation treatment. Prices relate to the period of 1998 to 2001 and were converted to Euro (euro), according to the official exchange rate of 1 euro = 1.95583 DM (1 euro approximately 0.90 US dollars; 2001 values). The comparative cost-effectiveness analysis covered a treatment period of more than one year. To estimate the net present value of future costs and effectiveness, a discount rate of 5% per year was applied. In the case of DMARD-naïve patients with RA, the sequence MTX, LEF, SSZ, IMG, AZA, CQ/HCQ was the most cost effective with direct costs of 7297 euro per ACR20RY and 6499 euro per QALY. In order to estimate the consequences of introducing LEF into the prescribing practice in Germany, the distribution of RA patients by individual DMARD in rheumatological care in 1998 was considered. This distribution was taken from the National Database of the German Collaborative Arthritis Centres. Though the sequences comprising LEF incurred 3% higher direct costs, they led to a higher effectiveness of 6% and 3% in the case of ACR20RYs and QALYs, respectively. Choosing sequences comprising LEF, there were additional direct costs of 5004 euro per ACR20RY gained and 8301 euro per QALY gained, as compared to the corresponding sequences without LEF. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. The contribution of LEF to the cost effectiveness of sequential DMARD therapy is obvious. The modeling study revealed advantages for the patients and the cost carriers. Though there were initially higher medication costs of the sequences comprising LEF, these costs were nearly compensated to remaining excess costs of just 3% after three years. This was caused by cost savings in other sectors of the health care system due to the higher effectiveness of the sequences comprising LEF.