Thromboembolic Safety Reporting of Tofacitinib and Baricitinib: An Analysis of the WHO VigiBase

Introduction The Janus kinase (JAK) inhibitors tofacitinib and baricitinib are new treatments for rheumatic diseases. Recent concerns regarding the risk of thrombosis have led to warnings by competent authorities. We therefore aimed to examine the thromboembolic safety signal for tofacitinib and baricitinib. Methods Individual case safety reports (ICSRs) for tofacitinib and baricitinib were retrieved from the World Health Organization global database VigiBase in April 2019. Primary outcomes were deep vein thrombosis (DVT) and pulmonary thrombosis (PT) or pulmonary embolism (PE). Patient demographics were summarized and then stratified by outcome. Disproportionality analyses were conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals (CIs) worldwide, and stratified by either Europe or the US. Results In both the tofacitinib (n = 40,017) and baricitinib (n = 2138) ICSRs, patients with reported DVT or PT/PE were older and had higher reporting of prothrombotic medications or antithrombotic treatments, suggesting a pre-existing thromboembolic risk/event. In Europe, tofacitinib was associated with increased reporting for DVT (ROR 2.37, 95% CI 1.23–4.56) and PT/PE (ROR 2.38. 95% CI 1.45–3.89). For baricitinib, a threefold increased reporting odds was observed for DVT (ROR 3.47, 95% CI 2.18–5.52) and PT/PE (ROR 3.44, 95% CI 2.43–4.88) in Europe. In the US, tofacitinib was only associated with an elevated ROR of PT (ROR 2.05, 95% CI 1.45–2.90) and no baricitinib ICSRs were reported. Conclusion This study supports the current recommendation for cautious use of tofacitinib in patients with high thromboembolic risk. Moreover, with a similar patient profile and elevated reporting for baricitinib, a potential class effect of JAK inhibitors cannot be ruled out.