RISK FACTORS FOR COLECTOMY FOLLOWING JANUS KINASE INHIBITOR RESCUE THERAPY IN ACUTE SEVERE ULCERATIVE COLITIS: AN INDIVIDUAL PARTICIPANT DATA META-ANALYSIS

Abstract INTRODUCTION Janus kinase inhibitor (JAKi) therapy, including tofacitinib and upadacitinib, has been increasingly used as rescue therapy for acute severe ulcerative colitis (ASUC). However, risk factors associated with non-response to JAKi rescue therapy and need for colectomy have not been well defined. METHODS We systematically searched PubMed to identify real-world observational studies reporting the use of JAKi as rescue therapy in adult patients with ASUC. Studies including more than 2 patients with available patient-level data were included in an individual participant data (IPD) meta-analysis. Associations between patient characteristics and 30-day colectomy after JAKi rescue therapy were assessed using a generalized linear mixed model. RESULTS Eighteen studies including 117 patients were included. The overall 30-day colectomy rate was 15.4%. Between-study heterogeneity was minimal (variance of the study-level random intercept=0.05). Fifty-six (54.9%) patients had prior exposure to anti-tumor necrosis factor (anti-TNF) therapy, which was significantly associated with a lower risk of 30-day colectomy in univariate analysis (OR 0.53, 95% CI 0.28–0.98, p = 0.04). In contrast, treatment with tofacitinib (n = 80 [68.4%]) versus upadacitinib (n = 37 [31.6%]) was associated with a higher risk of 30-day colectomy, although not statistically significant (OR 1.99, 95% CI 0.98–4.06, p = 0.06). After adjusting for JAKi type and age in multivariate analysis, prior exposure to anti-TNF therapy continued to appear associated with a reduced risk of 30-day colectomy (OR 0.31, 95% CI 0.08–1.13, p = 0.08). Endoscopic and laboratory parameters, including Mayo endoscopic score, ulcerative colitis endoscopic index of severity (UCEIS), C-reactive protein (CRP), hemoglobin, albumin, and fecal calprotectin (FCP), were not associated with 30-day colectomy. CONCLUSIONS In this one-stage IPD meta-analysis, prior exposure to anti-TNF therapy was significantly associated with reduced risk of 30-day colectomy following JAKi rescue therapy in ASUC, whereas treatment with tofacitinib versus upadacitinib appeared to be associated with increased risk. Common endoscopic indices and laboratory markers were not associated with 30-day colectomy and are unlikely to predict non-response to JAKi rescue therapy. These findings may help inform clinical decision-making regarding JAKi rescue therapy in ASUC and highlight the need for new biomarkers to identify patients at risk of non-response.