SAN DIEGO, CA—Tofacitinib may be a viable option for patients with moderate-to-severe rheumatoid arthritis (RA), according to a systematic review and meta-analysis reported at the 2013 ACR/ARHP Annual Meeting.
Tofacitinib, a small molecule inhibitor of the Janus kinase pathways central to the maintenance of the inflammatory state in rheumatoid arthritis, offers a different mechanism of action compared with other agents, noted Jean Tayar, MD, University of Texas MD Anderson Cancer Center, Houston, TX, and colleagues.
They conducted a comprehensive database search through October 2013 for any randomized controlled trial that compared tofacitinib alone or in combination with any disease-modifying anti-rheumatic drug (DMARD) vs. placebo or other DMARDs (traditional or biologic) for the treatment of patients with rheumatoid arthritis. Databases included Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, Web of Science, International Pharmaceutical Abstracts (IPA) database and Biological abstracts.
“Study selection, data collection and risk of bias assessment were performed by two independent reviewers,” Dr. Tayar noted. “We performed a meta-analysis when there was more than one study reporting in the percent of patients achieving an ACR50 response, clinical remission (DAS <2.6), discontinuations due to adverse events, and serious adverse events.”
Of 310 citations, 11 randomized controlled trials met inclusion criteria. Although most studies compared more than two doses of tofacitinib, the investigators only evaluated those that included the recommended dose, 5mg twice daily. Outcomes were analyzed at 12, 24, and 52 weeks.
The meta-analysis showed that at 6 to 24 weeks, a greater percentage of patients in the tofacitinib group achieved an ACR50 response (RR 3.4; 95% CI 2.3–5.0) and clinical remission (RR 3.1; 95% CI 1.4–6.7 vs. controls (eg, placebo + methotrexate). No differences between groups were observed in rate of discontinuations.
At 6 to 24 weeks, serious adverse events (AEs) were less likely to occur in the tofacitinib group vs. controls (RR 0.13; 95% CI 0.03–0.56). When tofacitinib was compared with adalimumab, similar rates of ACR50 response as well as discontinuations due to AEs and serious AEs were observed between groups.
Safety concerns with tofacitinib were identified as increased lipid, creatinine, and liver enzyme levels as well as decreased neutrophil count. “Oral tofacitinib 5mg twice daily could be beneficial for certain difficult to treat RA cases with appropriate monitoring for side effects,” the researchers concluded.