REMIT-UC: Real-World Effectiveness and Safety of Tofacitinib for Moderate-to-Severely Active Ulcerative Colitis: A Canadian IBD Research Consortium Multicenter National Cohort Study.

"CONFLICTS OF INTEREST Guarantor of the article: Christopher Ma, MD, MPH. Specific author contributions: Study conceptualization and design: C.M., R.P., F.P., B.B., V.J., T.B. Data collection: C.M., Y.X., Y.K., E.C.L.W., C.T., M.R.F., S.Y.S., R.S. Data analysis: C.M. Manuscript drafting: C.M. Manuscript editing for important intellectual content: all authors. All authors have approved the final version of this manuscript. Financial support: This study was cofunded by Canadian IBD Research Consortium (CIRC) and Pfizer. Pfizer and associated employees did not have access to any data. CIRC provided comments on the study design and input on data interpretation. All data collection was performed by CIRC investigators at each site; all data analyses were performed centrally at the University of Calgary. Potential competing interests: C.M. has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, and Roche; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Ferring, Janssen, Takeda, and Pfizer; research support from Ferring and Pfizer. R.P. has received consulting fees from Abbott, AbbVie, Alimentiv Inc Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, BioJAMP, Janssen, Merck, Mylan, Oppilan, Organon Pharma, Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, and Viatris; speaker's fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Fresenius Kabi, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; advisory boards fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, Glaxo-Smith Kline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Theravance Biopharma; and research/educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda Pharmaceuticals. Y.X., Y.K., S.M., and E.C.L.W. have no conflicts of interest. N.N. has received consulting fees from Iterative Scopes, Abbvie, Takeda, Janssen, and Pfizer; lecture fees from Janssen, Abbvie, Takeda, and Pfizer. C.T. has no conflicts of interest. F.P. has received speaker/advisory board fees from Janssen, AbbVie, Takeda, Pfizer, and Pharmascience. M.R.F. has no conflicts of interest. B.B. has received advisor/speaker fees: Ferring, Janssen, Abbvie, Takeda, Pfizer, Novartis, BMS, and Merck. Advisor: Alimentiv, Gilead, Iterative Scopes, AMT, Celgene, Microbiome Insights, Merck, Amgen, Pendopharm, Genentech, BMS, Allergan, Protagonist, Fresenius Kabi, Mylan, and Bausch Health; research support: Janssen, Abbvie, GSK, BMS, Amgen, Genentech, Merck, BI, Qu Biologic, Celgene, and Alvine; and stock options: Qu Biologic. S.Y.S. has no conflicts of interest. D.L. has received consulting fees for Abbvie, Amgen, Bristol Myers Squibb, Ferring, Fresenius-Kabi, Gilead, Janssen, McKesson, Merck, Organon, Pendopharm, Pfizer, Sandoz, Shire, Samsung, and Takeda and speaker fees from Abbvie, Amgen, Bausch, Ferring, Fresenius Kabi, Janssen, Lupin, Organon, Mylan, Pfizer, Sandoz, Shire, and Takeda. R.S. has no conflicts of interest to declare. V.J. has received advisory board/consulting fees from AbbVie, Alimentiv Inc. (formerly Robarts Clinical Trials Inc), Amgen, Applied Strategic, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Celgene/BMS, Celltrion, Eli Lilly, Ferring, F. Hoffman-La Roche Ltd, Flagship Pioneering, Fresenius Kabi, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Organon (Merck), Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion Therapeutics; speaker fees from Abbvie, Ferring, Galapagos, Janssen, Pfizer, and Takeda; and research support from Celgene/BMS, Pfizer, Abbvie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead Sciences, and Tigenix. T.B. has received consulting or speaker fees for Abbvie, Alimentiv, Amgen, Bristol Myers Squibb, Ferring, Janssen, Merck, Pfizer, Roche, Sandoz, Takeda, Gilead, Viatris, Fresenius, and Kabi. Study HighlightsWHAT IS KNOWN✓ Tofacitinib, a pan-Janus kinase inhibitor, is an effective treatment for patients with moderate-to-severely active ulcerative colitis (UC).✓ Concerns regarding the safety profile of Janus kinase inhibitors have been identified, although adverse events occurring in trial populations may not be generalizable to real-world practice.✓ During maintenance, the lowest dose of tofacitinib required to maintain remission is recommended, but some patients who dose reduce from 10 to 5 mg twice daily will lose response.WHAT IS NEW HERE✓ REMIT-UC is the largest multicenter, real-world cohort study of patients with UC treated with tofacitinib to date, including more than 375 patient-years of follow-up.✓ Nearly half of patients who de-escalate from 10 to 5 mg lost response, and this was only recaptured in half of patients who re-escalated treatment.✓ Patients with severe endoscopic activity and prior biologic failure are at over 3-fold increased risk for loss of response after dose reduction. Dose de-escalation must be considered judiciously in this population.✓ The safety profile of tofacitinib in this real-world cohort of younger patients with UC who are predominantly vaccinated against herpes zoster was reassuring, with low rates of venous thromboembolism and infections."

"Financial support: This study was cofunded by Canadian IBD Research Consortium (CIRC) and Pfizer. Pfizer and associated employees did not have access to any data. CIRC provided comments on the study design and input on data interpretation. All data collection was performed by CIRC investigators at each site; all data analyses were performed centrally at the University of Calgary."