Adverse drug events associated with 5mg versus 10mg Tofacitinib (Janus kinase inhibitor) twice daily for the treatment of autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials.

Several recently published clinical trials have shown tofacitinib to be effective in the treatment of autoimmune diseases. This drug is commonly prescribed either in a 5-mg or in a10-mg dosage twice daily. In this review, we aimed to systematically compare the adverse drug events which were observed with 5 mg versus 10 mg tofacitinib for the treatment of autoimmune diseases. MEDLINE, EMBASE, the Cochrane library, and www.ClinicalTrials.gov were searched (from March to April 2018) for suitable English publications (published before April 2018). The inclusion criteria were as follows: randomized controlled trials, autoimmune disorders (rheumatic arthritis, psoriatic arthritis, moderate to severe psoriasis, and ankylosing spondylitis), and comparison of adverse drug events associated with 5 mg versus 10 mg tofacitinib. This study had follow-up time periods of 3 months and ≥ 6 months. Statistical analysis was carried out by RevMan 5.3 whereby risk ratios (RRs) and 95% confidence intervals (CIs) were generated. A total number of 4287 participants were included (2144 versus 2143 participants who received 5 mg and 10 mg tofacitinib twice daily respectively). The results showed that at 3 months, similar risks of adverse drug events, serious adverse events, and adverse events leading to drug discontinuation were observed with 5 mg versus 10 mg tofacitinib (RR 1.04, 95% CI 0.98-1.10; P = 0.17, I2  = 0%; RR 1.06, 95% CI 0.77-1.48; P = 0.71, I2  = 0%; and RR 1.06, 95% CI 0.78-1.43; P = 0.73, I2  = 32%, respectively). The other outcomes including serious infection events, adjudicated herpes zoster infection, adjudicated opportunistic infection, mild and severe neutropenia, malignancies, and adjudicated major adverse cardiovascular events were also similarly manifested. However, a decreased level of hemoglobin significantly favored 5 mg tofacitinib (RR 1.75, 95% CI 1.19-2.58; P = 0.005, I2  = 49%). Even at a follow-up time period of ≥ 6 months, adverse drug events, serious adverse events, adverse drug events leading to drug discontinuation, and serious infection were still similarly observed. According to this current review, both dosages of tofacitinib were safe to use. Even if similar adverse drug events were observed with 5 mg versus 10 mg tofacitinib twice daily for the treatment of autoimmune disorders, anemia was more prominent with 10 mg tofacitinib at a 3 month follow-up. Nevertheless, future studies based on a larger population size with longer follow-up time periods should further be considered.