Characteristics and Outcomes of IBD Patients with COVID-19 on Tofacitinib Therapy in the SECURE-IBD Registry

INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented loss of life and health on a global scale.1 COVID-19 outcomes are more severe among those with comorbid conditions,1 which raises concerns for patients with inflammatory bowel disease (IBD), especially given the increased infection risk with immunosuppression used for IBD therapy. Tofacitinib is a Janus kinase inhibitor (JAKi) approved for the treatment of ulcerative colitis (UC)2 and other immunemediated diseases. Tofacitinib is associated with higher risk of herpes zoster (HZ) infection.2 Although HZ is a DNA virus, little is known regarding risks and outcomes of RNA viral infections such as SARS-CoV-2 with JAKi. Type 1 interferons, central to anti-SARS-CoV-2 activity and induced by the JAKSTAT pathway, were found to be impaired in severe COVID-19 in some studies and conversely upregulated in others, possibly reflecting heterogeneity in COVID-19 severity.3 Emerging data in non-IBD patients suggest that JAKi may blunt the cytokine storm that characterizes severe COVID-19 and potentially improve outcomes.4 In fact, a number of JAKi such as tofacitinib, baricitinib and ruxolitinib are being studied in clinical trials for COVID-19 treatment. Moreover, hospitalized COVID-19 patients are at a greater risk of thromboembolic events. This is important because findings from an interim analysis of a rheumatoid arthritis study for tofacitinib in older patients with ≥1 cardiovascular risk factor, alongside data from other JAKi clinical programs, suggest a higher risk of venous thromboembolic events.5 Emerging data on COVID-19 outcomes in patients with immune-mediated diseases treated with JAKi do not indicate worse outcomes compared with other immunosuppressive therapies; prior studies have been limited by very small sample sizes of fewer than 10 patients.6–9 To address this critical knowledge gap, we analyzed characteristics and outcomes of tofacitinib-treated IBD patients with COVID-19 compared with those on other medications in a global registry. applyparastyle "fig//caption/p[1]" parastyle "FigCapt"