Real-World Comparison of Tofacitinib vs Ustekinumab Among Bio-Exposed Patients With Ulcerative Colitis: A Propensity Score Analysis

Abstract

Over the last decade, therapies for moderate-to-severe ulcerative colitis (UC) have expanded to target not only tumor necrosis factor-alpha (TNF-α; infliximab, adalimumab, golimumab) agents but also α 4β 7 integrin (vedolizumab), interleukins 12 and 23 (ustekinumab), and Janus kinase inhibitors (tofacitinib). However, head-to-head clinical trials comparing these agents are limited,1 and optimal positioning of biologics is an area of ongoing investigation. A recent meta-analysis identified infliximab as the preferred first-line therapy for induction of clinical remission in patients who are biologic-naïve and either tofacitinib or ustekinumab as preferred agents after anti-TNF failure.2 However, many patients considering tofacitinib and ustekinumab, which were approved for UC after vedolizumab, have had anti-integrin failure as well. The OCTAVE trials of tofacitinib induction and maintenance therapy did not report the number of patients previously exposed to both anti-TNFs and vedolizumab.3 In the UNIFI trials of ustekinumab induction and maintenance therapy, only 17% of patients had prior exposure to both drug classes, among whom approximately 10% achieved remission at week 8.4 Nevertheless, the efficacies of tofacitinib and ustekinumab in this refractory population within real-world settings are poorly understood. We therefore sought to compare tofacitinib vs ustekinumab among patients with UC with prior anti-TNF and anti-integrin failure.