PMID- 38425446 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240302 IS - 2631-827X (Electronic) IS - 2631-827X (Linking) VI - 6 IP - 1 DP - 2024 Jan TI - Association Between Smoking Status and the Efficacy and Safety of Tofacitinib in Patients with Ulcerative Colitis. PG - otae004 LID - 10.1093/crocol/otae004 [doi] LID - otae004 AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). This analysis assessed the impact of cigarette smoking on tofacitinib efficacy and safety in the UC clinical program. METHODS: Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in the phase (P)2 induction study (baseline demographics and safety only), P3 studies (OCTAVE Induction 1&2, OCTAVE Sustain, OCTAVE Open), and P3/4b RIVETING study. RESULTS: This post hoc analysis included 1156 patients (ever smokers, n = 416 [36.0%; current smokers, n = 59 (5.1%); ex-smokers, n = 357 (30.9%)]; never smokers, n = 740 [64.0%]; median [range] treatment duration 654 [1-2712] and 615.5 [1-2850] days, respectively). Similar proportions of ever smokers and never smokers achieved efficacy endpoints. AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection (serious infections, 5.5%; herpes zoster [nonserious and serious], 10.8%; Clostridioides difficile infection, 12.0%; lower respiratory tract infection, 19.5%: corresponding values among never smokers were 53.1%, 3.9%, 6.8%, 8.5%, and 11.4%). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers and thromboembolism events (venous and arterial) in 1.0% of ever smokers and 0.9% never smokers. Deaths, malignancies (excluding non-melanoma skin cancer [NMSC]), and NMSC occurred infrequently in ever smokers (0.5%, 2.5%, and 3.7%, respectively) and never smokers (0.1%, 1.5%, and 1.0%, respectively). Colorectal cancer was reported in 0.6% of never smokers; no cases occurred in ever smokers. CONCLUSIONS: Efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. Overall, serious AEs and, as expected, infections were more frequent in ever smokers versus never smokers. This may inform treatment selection and monitoring strategies. CLINICALTRIALSGOV: NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation. FAU - Rubin, David T AU - Rubin DT AD - Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL, USA. FAU - Torres, Joana AU - Torres J AUID- ORCID: 0000-0003-2895-5821 AD - Gastroenterology Division, Hospital Beatriz Angelo, Loures, Portugal. AD - Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal. AD - Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. FAU - Regueiro, Miguel AU - Regueiro M AUID- ORCID: 0000-0002-7681-8111 AD - Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH, USA. FAU - Reinisch, Walter AU - Reinisch W AUID- ORCID: 0000-0002-2088-091X AD - Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Prideaux, Lani AU - Prideaux L AD - Department of Gastroenterology and Hepatology, Monash Medical Centre, Melbourne, Victoria, Australia. FAU - Kotze, Paulo G AU - Kotze PG AD - IBD Outpatient Clinics, Colorectal Surgery Unit, Catholic University of Parana, Curitiba, Brazil. FAU - Tan, Fiona H AU - Tan FH AUID- ORCID: 0000-0002-1599-0997 AD - Pfizer Australia, Melbourne, Victoria, Australia. FAU - Gardiner, Sean AU - Gardiner S AUID- ORCID: 0009-0008-9193-9844 AD - Pfizer Inc, New York, NY, USA. FAU - Mundayat, Rajiv AU - Mundayat R AD - Pfizer Inc, New York, NY, USA. FAU - Cadatal, Mary Jane AU - Cadatal MJ AD - Pfizer Inc, Manila, Philippines. FAU - Ng, Siew C AU - Ng SC AD - Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, Chinese University of Hong Kong, Sha Tin, Hong Kong, China. LA - eng SI - ClinicalTrials.gov/NCT01458574 SI - ClinicalTrials.gov/NCT03281304 SI - ClinicalTrials.gov/NCT01465763 SI - ClinicalTrials.gov/NCT01470612 SI - ClinicalTrials.gov/NCT01458951 PT - Journal Article DEP - 20240120 PL - England TA - Crohns Colitis 360 JT - Crohn's & colitis 360 JID - 101752188 PMC - PMC10904100 OTO - NOTNLM OT - Janus kinase inhibitor OT - cigarette OT - inflammatory bowel disease OT - ulcerative colitis COIS- D.T.R. has received grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim Ltd., Bristol Myers Squibb, Dizal Pharmaceuticals, Galapagos, Ichnos Sciences, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Lilly, Pfizer Inc, Prometheus Biosciences, Reistone, S.A., and Syneos. J.T. has served as an advisory board member for AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Galapagos, Janssen, and Pfizer Inc, has received research funding from AbbVie and Janssen, and has received lecture fees from AbbVie, Galapagos, Janssen, and Pfizer Inc. M.R. has served as an advisory board member or consultant for AbbVie, Amgen, Celgene, Janssen, Miraca Labs, Pfizer Inc, Seres Therapeutics, Takeda, and UCB, has received research funding from AbbVie, Janssen, and Takeda, and has received unrestricted educational grants from AbbVie, Janssen, Pfizer Inc, Salix, Shire, Takeda, and UCB. W.R. has served as a speaker for AbbVie, Celltrion, Falk Pharma GmbH, Ferring, Galapagos, Janssen, MSD, Pfizer Inc, Pharmacosmos, Roche, Shire, Takeda, and Therakos, has served as a consultant for AbbVie, Amgen, AOP Orphan, Arena Pharmaceuticals, Astellas, AstraZeneca, Bioclinica, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celgene, Celltrion, Eli Lilly, Falk Pharma GmbH, Ferring, Galapagos, Gatehouse Bio Inc, Genentech, Gilead Sciences, Grunenthal, ICON, InDex Pharmaceuticals, Inova, Janssen, Landos Biopharma, MedAhead, MedImmune, Microbiotica, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pfizer Inc, Pharmacosmos, Protagonist, Provention, Quell Therapeutics, Sandoz, Seres Therapeutics, SetPoint Medical, Sigmoid, Sublimity, Takeda, Teva Pharmaceuticals, Therakos, Theravance, and Zealand, has served as an advisory board member for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Galapagos, Janssen, Mitsubishi Tanabe Pharma Corporation, MSD, Pharmacosmos, Pfizer Inc, Sandoz, and Takeda, and has received research funding from AbbVie, Janssen, MSD, Sandoz, Sanofi, and Takeda. L.P. has no conflicts of interest to declare. P.G.K. has served as a consultant or speaker for AbbVie, Janssen, Pfizer Inc, and Takeda, and has received research funding from Pfizer Inc and Takeda. F.H.T., S.G., R.M., and M.J.C. are employees and stockholders of Pfizer Inc. S.C.N. has served as a speaker for AbbVie, Ferring, Janssen, Menarini, Pfizer Inc, Takeda, and Tillotts, has received research funding from AbbVie, Ferring, and Olympus, and holds a directorship with Microbiota I-Center. EDAT- 2024/03/01 06:44 MHDA- 2024/03/01 06:45 PMCR- 2024/01/20 CRDT- 2024/03/01 03:46 PHST- 2023/06/13 00:00 [received] PHST- 2024/03/01 06:45 [medline] PHST- 2024/03/01 06:44 [pubmed] PHST- 2024/03/01 03:46 [entrez] PHST- 2024/01/20 00:00 [pmc-release] AID - otae004 [pii] AID - 10.1093/crocol/otae004 [doi] PST - epublish SO - Crohns Colitis 360. 2024 Jan 20;6(1):otae004. doi: 10.1093/crocol/otae004. eCollection 2024 Jan.