Methotrexaat effectiever dan azathioprine bij actieve ernstige reumatoïde artritis

To determine the effectiveness of low-dose methotrexate in the treatment of severe rheumatoid arthritis, compared with that of azathioprine.

Design

Double-blind randomised 48-week trial.

Patients and method

Sixty-four patients with active rheumatoid arthritis, who either had not responded to or had suffered side effects on at least parenteral gold and penicillamine. Either azathioprine, 100 mg daily, or methotrexate, 7.5 mg weekly, was administered orally. Depending on the clinical effect after 8 weeks, the dosage was increased to either azathioprine, 150 mg or methotrexate, 15 mg. The dosages for nonsteroidal anti-inflammatory drugs and prednisone were held stable. Clinical and laboratory assessments were done every 4 weeks during the first 6 months and every 2 months thereafter, until the forty-eighth week.

Results

After 24 weeks the methotrexate group showed significantly more improvement in the clinical and laboratory parameters than the azathioprine group (12 of 13 versus 6 of 13). The difference in improvement between the azathioprine group and the methotrexate group was significant for the number of swollen joints, ESR and haemoglobin (p < 0.02). An area-under-the-curve analysis for 24 weeks showed significantly more improvement in the MTX group for pain score, number of swollen joints, ESR, C-reactive protein, and thrombocytes count. An intention-to-treat analysis after 24 weeks gave the same results except for swollen joints. After 48 weeks the differences in both treatment groups were not significant. The immunoglobulin levels IgA, IgG and IgM at 24 weeks and 48 weeks were decreased by 10-25 and the mean rheuma factor titre by the latex fixation test was decreased by more than 60 (p = 0.001) in both groups. The number of withdrawals due to side effects was significantly higher in the azathioprine group.

Conclusions

In this trial methotrexate was superior to azathioprine in the treatment of RA. The earlier and more sustained clinical improvement in methotrexate-treated patients was accompanied by a significantly lower rate of serious side effects.