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.
Objective. To summarize the potential predictors of remission in patients with rheumatoid arthritis (RA). Methods. We performed a systematic review of prognostic studies that identified the predictors of remission in RA patients. Studies were identified in Medline, EMBase, and the Cochrane Registry, and by hand search. We included only studies performing multivariate analysis. Results. A total of 18 studies from 2,062 citations were included. The following variables were found to be the independent predictors of RA remission: male sex; young age; late-onset RA; short disease duration; nonsmoker; low baseline disease activity; mild functional impairment; low baseline radiographic damage; absence of rheumatoid factor and anti-citrullinated peptide; low serum level of acute-phase reactant, interleukin-2, and RANKL at baseline; MTHFR 677T alleles and 1298C alleles in the methotrexate (MTX)-treated patients; magnetization transfer ratio 2756A allele ؎ either the SLC 19A180A allele or the TYMS 3R-del6 haplotype in the MTX plus sulfasalazine combination-treated patients; early treatment with nonbiologic disease-modifying antirheumatic drug (DMARD) combinations; the use of anti-tumor necrosis factor (anti-TNF); the concurrent use of DMARDs in anti-TNF-treated patients; and moderate or good response to treatments at the first 6 months. The magnitude of the association in the individual predictor was diverse among the studies depending on the patient characteristics, the study characteristics, and the variables used to adjust for in the models. Conclusion. A number of independent predictors of remission, i.e., baseline clinical and laboratory characteristics and genetic markers, were summarized. The predictive value of prognostic factors recently identified needs to be confirmed.
Anti-tumor necrosis factor-α agents may improve inflammatory arthritis and disability in SSc. The effect on skin score is uncertain. Adequately powered trials are needed to evaluate efficacy, and longitudinal studies are needed to evaluate longterm safety of these agents in SSc.
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