Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis

Abstract

Objective:To evaluate the efficacy and toxicity of methotrexate (MTX) monotherapy compared with MTX combination with non-biological disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis.Method:A systematic review of randomised trials comparing MTX alone and in combination with other non-biological DMARDs was carried out. Trials were identified in Medline, EMBASE, the Cochrane Library and ACR/EULAR meeting abstracts. Primary outcomes were withdrawals for adverse events or lack of efficacy.Results:A total of 19 trials (2025 patients) from 6938 citations were grouped by the type of patients randomised. Trials in DMARD naive patients showed no significant advantage of the MTX combination versus monotherapy; withdrawals for lack of efficacy or toxicity were similar in both groups (relative risk (RR) = 1.16; 95% CI 0.70 to 1.93). Trials in MTX or non-MTX DMARD inadequate responder patients also showed no difference in withdrawal rates between the MTX combo versus mono groups (RR = 0.86; 95% CI 0.49 to 1.51 and RR = 0.75; 95% CI 0.41 to 1.35), but in one study the specific combination of MTX with sulfasalazine and hydroxychloroquine showed a better efficacy/toxicity ratio than MTX alone with RR = 0.3 (95% CI 0.14 to 0.65). Adding leflunomide to MTX non-responders improved efficacy but increased the risk of gastrointestinal side effects and liver toxicity. Withdrawals for toxicity were most significant with ciclosporin and azathioprine combinations.Conclusion:In DMARD naive patients the balance of efficacy/toxicity favours MTX monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used MTX doses and combination therapies.

The effect of low-dose methotrexate on autologous fat graft survival

“…LD-MTX was recently reported to be an inhibitor of lymphocyte proliferation and the destructive capacity of leukocytes that reach the inflammatory area (14). It also promotes extracellular adenosine accumulation at the inflammatory site, which inhibits some cytokines, superoxide, nitric oxide, and TNF-α (14,15).…”

“…It also promotes extracellular adenosine accumulation at the inflammatory site, which inhibits some cytokines, superoxide, nitric oxide, and TNF-α (14,15). Adenosine is a cytoprotective molecule due to its inhibitor effect on toxic oxygen metabolites created from the adhesion of stimulated neutrophils to the endothelium (11,16).…”

Effects of low-dose methotrexate in spinal cord injury in rats

“…[1] Recently, low-dose methotrexate (MTX) has become the mainstay in the treatment of some inflammatory diseases such as rheumatoid arthritis. [3,4] Chronstein et al [3] showed that low-dose MTX can inhibit both proliferation of lymphocytes in an inflammatory exudate and reduce the destructive capacity of the leukocytes that do arrive at the inflammation site. Although its exact mechanism of action has not been clarified yet, low-dose MTX promotes extracellular adenosine accumulation at the inflammation sites.…”

Drug Rediscovery to Prevent O-Label Prescription Reduces Health Care Costs: the Case of Tioguanine in e Netherlands

“…Methotrexate in rheumatoid arthritis has shown robust on-label evidence for e cacy over the years [3]. Aspirin, developed as a painkiller more than 100 years ago, is nowadays widely and successfully used in cardiology and neurology, and can perhaps in the near future be used to decrease the risk of developing cancer [4].…”