Methotrexate is a disease-modifying antirheumatic drug suitable for moderate to severe rheumatoid arthritis. Azathioprine, ciclosporin, cyclophosphamide, leflunamide and the cytokine modulators are considered more toxic and they are used in cases that have not responded to other disease-modifying drugs.

Methotrexate is given once weekly, dose adjusted according to response. In patients who experience mucosal or GI side effects with methotrexate, folic acid given every week [unlicensed indication] on a different day from the methotrexate, may help to reduce the frequency of such side effects.

Leflunomide acts on the immune system as a DMARD, its therapeutic effect starts after 4-6 weeks and improvement may continue for a further 4-6 months. Leflunomide, which is similar in efficacy to sulfasalazine and methotrexate, may be chosen when these drugs cannot be used.

Ciclosporin is licensed for severe active rheumatoid arthritis when conventional second line tharapy is inappropriate or ineffective. There is some evidene that ciclosporin may retard the rate of erosive progression and improve symptom control in those who respond only partially to methotrexate.