Tofacitinib for acute rheumatoid arthritis patients who have had an inadequate response to disease-modifying antirheumatic drug (DMARD): a systematic review and meta-analysis

Abstract

The aim of this systematic review and meta-analysis is to assess the efficacy and safety of tofacitinib for the treatment of patients with acute rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drug (DMARD). Randomized controlled trials were searched in MEDLINE (1966-2013), Embase (1947-2013), the Cochrane Central Register of Controlled Trials (1948-2013), WHO International Clinical Trial Registration Platform (2004-2013), Clinical Trial.gov (1999-2013), and China Biology Medicine disc (1978-2013). The review included 10 studies involving 4,929 patients. A pooled analysis of six studies showed that tofacitinib had a superior effect over placebo (both with background therapy) at weeks 12 and 24. Also, the pooled results of three studies showed that tofacitinib monotherapy had a significantly greater effect over placebo. Compared to adalimumab, tofacitinib was found to be more efficacious as well. For safety, tofacitinib monotherapy had less serious adverse events (sAE) than placebo but not other adverse effects (oAE). In the comparison of tofacitinib and placebo both with background therapy, no difference in sAE and oAE were found. However, the quality of the evidence was quite low when evaluated using GRADE. Tofacitinib alone, or together with non-biologic DMARDs, was associated with more favorable remission in the signs and symptoms of RA than adalimumab or placebo. Also, tofacitinib monotherapy was safer than placebo with regards to reported sAE, but not oAE. However, the quality of evidence is exceedingly low; long-term, large-scale, and high-quality post-marketing research is suggested to further verify the conclusion.

The molecular regulation of Janus kinase (JAK) activation

“…Ruxolitinib™ treatment substantially reduced spleen size and improved quality of life in a significant proportion of patients with myelofibrosis but, surprisingly, treatment was also effective in patients without mutated JAK2 and there was not convincing evidence of reduction in mutated allele burden or progression to AML [58, 59]. Tofacitinib™ was more effective in improving symptoms in rheumatoid arthritis than placebo or existing anti-TNF receptor therapy [60]. While some of these results are promising, it is clear that a better understanding of the specificity of JAK inhibitors is required to draw firm conclusions about optimal therapies for these diseases.…”

Impact of tofacitinib on patient outcomes in rheumatoid arthritis – review of clinical studies

“…These findings are similar to findings reported in prior meta-analyses, but this review includes all patient-centered outcomes mentioned in the studies reviewed and also includes data from more recent studies. 14 , 16 Measurements of patient’s pain and global assessment of disease demonstrated that tofacitinib 5 mg bid was more effective than both placebo and tofacitinib 1–3 mg bid in both monotherapy and combination therapy studies.…”

2016 updated Thai Rheumatism Association Recommendations for the use of biologic and targeted synthetic disease‐modifying anti‐rheumatic drugs in patients with rheumatoid arthritis

“…The combination of anti‐TNFα and MTX had a better response than anti‐TNFα alone, despite certain anti‐TNFα being suggested as monotherapy . Tofacitinib in active RA patients with inadequate response or intolerance to csDMARDs showed similar results to bDMARDs . Etanercept, tocilizumab and tofacitinib are very effective in reducing signs and symptoms even when used as monotherapy.…”