Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
Rheumatoid arthritis is a chronic inflammatory disorder that mainly affects the peripheral joints and surrounding tissue.
It usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions.The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
The DMARD methotrexate is widely used as first-line treatment in people with rheumatoid arthritis because of consensus about its effectiveness in practice.
Sulfasalazine and combined treatment with methotrexate and sulfasalazine are as effective as methotrexate in improving pain, joint swelling, and function in people with early rheumatoid arthritis who have not previously received DMARDs.
Antimalarials may improve symptoms and function in DMARD-naïve people, and are reasonably well tolerated, but radiological evidence of erosion is more marked with antimalarials than with sulfasalazine.
There is a variety of DMARDs available for second-line treatment of rheumatoid arthritis, and we found no clear evidence that one is superior.
Methotrexate, sulfasalazine, penicillamine , and leflunomide cause similar improvements in symptoms and function when given to people as second-line DMARD treatment, although methotrexate causes fewer adverse effects.The combination of methotrexate plus sulfasalazine plus hydroxychloroquine is more effective in reducing measures of disease activity in people receiving second-line treatment than any of the drugs used alone. Adding the cytokine inhibitors infliximab or etanercept to methotrexate is more effective than using methotrexate alone.Although antimalarials and oral gold seem to improve clinical disease activity when given as second-line treatment, they are not as effective as methotrexate or sulfasalazine. Although parenteral gold is more effective than oral gold, it leads to higher levels of toxicity than most of the other commonly used DMARDs.
Ciclosporin offers short-term control of rheumatoid arthritis when used as second-line treatment, but is associated with nephrotoxicity.We don′t know whether cyclophosphamide is as effective as other DMARDs for second-line treatment.Cytokine inhibitors may offer an alternative to traditional DMARDs for second line treatment of rheumatoid arthritis, but more research is needed.
Etanercept may be as effective as methotrexate in improving symptoms, function, and radiological evidence of progression, but more evidence for its effect is needed
Azathioprine is less effective and is less well tolerated than methotrexate.We don't know whether anakinra or adalimumab are as effective as other DMARDs for second-line treatment.Although widely used for the initial short-term relief of clinical disease activity in rheumatoid arthritis, we don't know how corticosteroids compare with other drugs for first or second-line treatment.