Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry
Biemans, Vince B C; Sleutjes, Jasmijn A M; de Vries, Annemarie C; Bodelier, Alexander G L; Dijkstra, Gerard; Oldenburg, Bas; Löwenberg, Mark; van Bodegraven, Adriaan A; van der Meulen-de Jong, Andrea E; de Boer, Nanne K H; Srivastava, Nidhi; West, Rachel L; Römkens, Tessa E H; Horjus Talabur Horje, Carmen S; Jansen, Jeroen M; van der Woude, C Janneke; Hoekstra, Jildou; Weersma, Rinse K; van Schaik, Fiona D M; Hoentjen, Frank; Pierik, Marieke J; Dutch Initiative on Crohn and Colitis (ICC)
(2020) Alimentary Pharmacology & Therapeutics, volume 51, issue 9, pp. 880 - 888
(Article)
Abstract
BACKGROUND: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). AIM: To evaluate effectiveness, safety and use of tofacitinib in daily practice. METHODS: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI]
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≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. RESULTS: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. CONCLUSION: Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.
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Keywords: real world, tofacitinib, ulcerative colitis, Prospective Studies, Humans, Middle Aged, Antibodies, Monoclonal, Humanized/therapeutic use, Male, Pyrroles/therapeutic use, Treatment Outcome, Pyrimidines/therapeutic use, Crohn Disease/drug therapy, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Piperidines/therapeutic use, Colitis, Ulcerative/drug therapy, Protein Kinase Inhibitors/therapeutic use, Adult, Female, Registries, Ustekinumab/therapeutic use, Netherlands/epidemiology, Gastroenterology, Pharmacology (medical), Hepatology, Journal Article, Observational Study
ISSN: 0269-2813
Publisher: Wiley-Blackwell
Note: Funding Information: : VBC Biemans has no conflicts of interest to declare. JAM Sleutjes has no conflicts of interest to declare. AC de Vries has participated in advisory board and/or received financial compensation from the following companies: Jansen, Takeda, Abbvie and Tramedico. AGL Bodelier has served as speaker and/ or participant in advisory board for: Abbvie, Merck Sharp & Dohme, Takeda, Vifor Pharma, Mundipharma. G. Dijkstra has unrestricted research grants from Abbvie and Takeda. Advisory boards for Mundipharma and Pharmacosmos. Received speakers fees from Abbvie, Takeda and Janssen Pharmaceuticals. B. Oldenburg speaker: Ferring, MSD, Abbvie. Advisory boards: Ferring, MSD, Abbvie, Takeda, Pfizer, Janssen. Research Grants: Abbvie, Ferring, Takeda, Pfizer, MSD, Dr Falk. M. Löwenberg has served as speaker and/or principal investigator for: Abbvie, Celgene, Covidien, Dr Falk, Ferring Pharmaceuticals, Gilead, GlaxoSmithKline, Janssen‐Cilag, Merck Sharp & Dohme, Pfizer, Protagonist therapeutics, Receptos, Takeda, Tillotts, Tramedico. He has received research grants from AbbVie, Merck Sharp & Dohme, Achmea healthcare and ZonMW. AA van Bodegraven has served as speaker, adviser and/or principal investigator for AbbVie, Arandal, Arena, Celgene, Ferring, Janssen, MSD, Pfizer, Roche, Takeda, TEVA, and received research grants from TEVA, Eurostars funding, ZonMW. AE van der Meulen—de Jong has served on advisory boards, or as speaker or consultant for Takeda, Tramedico, AbbVie, and has received grants from Takeda. NKH de Boer has served as a speaker for AbbVie, Takeda and MSD. He has served as consultant and principal investigator for Takeda and TEVA Pharma BV He has received (unrestricted) research grants from Dr Falk and Takeda. N. Srivastava has no conflict of interest to declare. RL West has participated in advisory board and/or received financial compensation from the following companies: Jansen and Abbvie. TEH Römkens has participated in advisory board and/or received financial compensation from the following company: Takeda. CS Horjus Talabur Horje has no conflicts of interest to declare. JM Jansen has served on advisory boards, or as speaker or consultant for Abbvie, Amgen, Ferring, Fresenius, Janssen, MSD, Pfizer, Takeda. CJ van der Woude has served on advisory boards and/or received financial compensation from the following companies: MSD, FALK Benelux, Abbott laboratories, Mundipharma Pharmaceuticals, Janssen, Takeda and Ferring during the last 3 years. J. Hoekstra has no conflicts of interest to declare. RK Weersma received unrestricted research grants from Takeda, Tramedico and Ferring. FDM van Schaik has served on the advisory board of Dr Falk. F. Hoentjen has served on advisory boards, or as speaker or consultant for Abbvie, Celgene, Janssen‐Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk, and has received unrestricted grants from Dr Falk, Janssen‐Cilag, Abbvie. MJ Pierik has served on advisory boards, or as speaker or consultant for Abbvie, Janssen‐Cilag, MSD, Takeda, Ferring, Dr Falk and Sandoz and has received unrestricted grants from, Janssen‐Cilag, Abbvie and Takeda outside the submitted work. Declaration of personal interests Publisher Copyright: © 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd
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