Efficacy and safety of a combination therapy of methotrexate, chloroquine and cyclophosphamide in patients with refractory rheumatoid arthritis: results of an observational study with matched-pair analysis.

The efficacy and safety of a combination of methotrexate (MTX), chloroquine (CQ) and cyclophosphamide (CYC) were studied in patients with refractory rheumatoid arthritis. A single-centre, matched-pair observational study with prospectively gathered data was performed. Fifty-six patients who had previously failed with MTX were treated with 15 mg MTX per week, 50 mg CYC three times a week and 250 mg CQ per day (group A). A 50% improvement of the swollen joint count was required to continue therapy. Data were compared with the results of the previous MTX therapy in the same group and with a matched-patient cohort receiving MTX monotherapy for the first time (group B). In group A, the combination therapy resulted in a significant decline of the swollen joint count after 1 year, in contrast to the previous MTX monotherapy in the same group. Complete remission of joint swelling was achieved in 13 patients (23%), compared with 26 patients in group B (47%). The median duration of effective combination treatment in group A was significantly longer than preceding therapies with MTX alone (19 vs 13 months, p<0.05). However, patients in group B could be treated for a median of 57.5 months (p<0.0001 compared with group A). Side-effects were comparable in both groups. The applied DMARD combination is safe and beneficial in a significant proportion of patients if MTX monotherapy is ineffective.