Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus

To evaluate the capacity of methotrexate (MTX) to control mild activity of systemic lupus erythematosus (SLE), and to evaluate the capacity of MTX to reduce steroid requirement, as well as to evaluate the side effects of MTX in patients with SLE.

A prospective, randomized, controlled, double blind trial. Forty-one patients with SLE began and 37 completed the 6 months of study. The mean disease duration was 82.5 months. Twenty patients received MTX 15-20 mg/week (MTX group) and 21 received placebo (PL group). The dose of prednisone was maintained, increased, or reduced after the first month, according to monthly clinical and laboratory evaluation. Dose of prednisone, SLE Disease Activity Index (SLEDAI) scores, the score by visual analog scale (VAS) for articular pain, and laboratory results were recorded monthly. Both groups were homogeneous and comparable for clinical manifestations and laboratory results.

Two placebo patients dropped out due to severe flare of disease requiring hospitalization, and 2 patients taking MTX dropped out due to side effects (one with pulmonary tuberculosis, one with urticaria and severe dyspepsia). Thirty-seven patients (18 MTX and 19 PL) completed the study. At the end of the study 16 PL patients and one MTX patient presented articular complaints (p < 0.001). VAS scores for pain were significantly higher in the PL group than in the MTX group after the first month of study. Sixteen PL patients and 3 MTX patients presented cutaneous lesions after 6 months of treatment (p < 0.001). At the end of the study 4 MTX patients and 11 PL patients presented hypocomplementemia (p < 0.001). Mean SLEDAI scores in PL patients were significantly higher than in MTX patients at Months 3, 4, 5, and 6. It was possible to decrease the prednisone dose for 13 MTX patients during the study but for only one PL patient (p < 0.001). Fourteen MTX patients (70%) presented side effects, mainly dyspepsia and increase in hepatic enzyme serum levels, and 3 PL patients (14%) presented dyspepsia.

MTX 15 to 20 mg/week for 6 months was effective in controlling cutaneous and articular activity of SLE and permitted prednisone dose reduction. At these doses MTX presented frequent but mild side effects that did not result in drug discontinuation in the majority of patients.