Effectiveness profiles and dose dependent retention of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. An observational study

Objective. To determine the fate of traditional disease modifying antirheumatic drugs (DMARD) in the longer term, with special respect to dose related effects on drug retention rates, efficacy, and toxicity. Methods. Historical analysis of DMARD therapies in 593 patients, comprising a total of 1319 courses of DMARD over a period of 2378 patient-years of therapy. DMARD dosages, treatment durations, and reasons for discontinuation, and measures of C-reactive protein and erythrocyte sedimentation rate were analyzed. Drug retention rates were estimated by Kaplan-Meier analysis. Results. Methotrexate (MTX), chloroquine, and sulfasalazine (SSZ) emerged as the drugs most commonly applied during the past 15 years, whereas gold salts and D-penicillamine became less frequently used during the past decade. Therapies had to be terminated mostly for adverse events (42%) or inefficacy (37%). Patients taking high dose therapy had significantly longer median retention rates than those taking low doses (SSZ 34 vs 7 mo; MTX 73 vs 39 mo). Toxicity, rather than inefficacy, was the main reason for discontinuation of MTX and SSZ at low doses (p < 0.001). Median retention rates lasted < 24 mo for most DMARD, except for high dose MTX (> 36 mo). Conclusion. MTX, SSZ, and antimalarials have become the most commonly used traditional DMARD for rheumatoid arthritis. Their use is more often limited by toxicity than by inefficacy. If tolerated, they can be retained for long periods of time.