To evaluate the effectiveness of disease-modifying antirheumatic drugs, namely, methotrexate (MTX), sulfasalazine (SSZ) and bucillamine (BUC) at low-doses (4, 6 or 8 mg MTX, 500 or 1,000 mg SSZ, and 100 or 200 mg BUC) in 1,358 patients with a follow-up of at least 12 months and more than 120 months.
Clinical assessments were based on the number of painful joints (NPJ) and that of swollen joints (NSJ), CRP level, erythrocyte sedimentation rate, rheumatoid factor level and morning stiffness before and after treatment. Results were evaluated on the basis of the duration of treatment for each drug with inefficacy or inadequate efficacy as one endpoint for discontinuation and adverse drug reactions (ADRs) as the other in single agent and combination therapy. The incidence and nature of ADRs in single and combination treatment are described.
The effects of MTX, SSZ and BUC on clinical parameters were monitored over the first three months, and in particular, NPJs and NSJs were found to decrease significantly during single agent MTX or BUC treatment over 108 months. CRP levels remained significantly improved for more than 120 months with MTX. In the single and combination long-term treatments, continuation rate with inefficacy or inadequate efficacy as the end point achieved for each of the treatments were 83.1% for MTX, 76.0% for BUC, 68.5% for SSZ, and in the case of the combination treatments, these rates were 83.3% for MTX + BUC and 71.0% for MTX+SSZ. Continuation rates using ADRs as the end point were 88% for SSZ, 79.6% for BUC and 79.4% for MTX. The incidences of ADRs for the various treatments were: MTX 22.2%, SSZ 11.0%, BUC 20.6%, MTX + BUC 30.0% and MTX + SSZ 31.2%.
MTX showed the highest efficacy even though it was administrated at a low dose (6-8 mg), as a single agent or in combination with other treatment. However, in combination treatments, the continuous duration of treatment ending in ADRs as the end point were lower than those in single treatments with MTX, SSZ and BUC.