GENDER DOES NOT INFLUENCE CLINICAL RESPONSE TO JAK INHIBITORS IN RHEUMATOID ARTHRITIS: AN ITALIAN MULTICENTRE ANALYSIS

Background: According to preliminary analysis of study A3921133, tofacitinib10 mg twice daily was associated with increased occurrence of all-cause mortality and pulmonary embolism compared with anti-tumor necrosis factor (anti-TNF), whereas 5 mg tofacitinib twice daily exhibited similar safety profile with anti-TNF. Objectives: We aim to investigate the role of Janus kinase inhibitors (Jakinibs) in all-cause mortality among RA population via a meta-analysis of RCTs. Methods: PubMed, Embase and Cochrane Library were systemically searched for RCTs reporting adverse events in RA patients receiving Jakinibs, from inception to October 2018. Absolute risk differences (RD) and 95% confidence interval (CI) were used as an effect measure using the Mantel-Haenszel fixed-effect method. Results: A total of 31 RCTs randomizing 13,065 patients met the inclusion criteria. During the placebo-controlled phase, there were 16 and 6 deaths in Jakinibs and placebo respectively, accompanied by a numerically higher absolute incidence mortality rate in Jakinibs than in placebo (0.651 vs. 0.531 per 100 patient-years). In direct pairwise comparisons, 2,194 and 2,246 patient-years of exposure in lower and higher Jakinibs reported a total of 19 deaths (10 with lower dose [0.456 per 100 patient-years] and 9 with higher dose [0.401 per 100 patient-years]). Compared with placebo, no significant difference was observed in tofacitinib (RD,0.01 events/person-year; 95% CI, -0.01 to 0.02; P =0.52); barictinib (RD,-0.00 events/person-year; 95% CI, -0.01to 0.01; P =0.59); upadacitinib (RD,0.00 events/person-year; 95% CI, -0.02to 0.03; P =0.71); perficitinib (RD,0.00 events/person-year; 95% CI, -0.05 to 0.06; P =0.86); decernotinib (RD,0.02 events/person-year; 95% CI, -0.03 to 0.06; P =0.44); fligotinib (RD,0.00 events/person-year; 95% CI, -0.05 to 0.06; P=0.85). In pairwise comparisons, no dose-dependent impact of Jakinibs on all-cause mortality was not observed in tofacitinib (5mg vs. 10mg, bid), baricitinib (2mg vs. 4mg, qd) upadacitinib (15mg vs. 30mg, qd). Conclusion: Compared with placebo, there was no significant difference in the all-cause mortality rate observed in patients receiving Jakinibs treatments, but post-marketing data in real-life setting are sorely needed to ascertain their safety in general population. Large, prospective, well-designed studies are needed to explore the effects of such drugs on diabetes development in the RA patients with high-risk diabetes. Disclosure of Interests: None declared