PMID- 36124702
OWN - NLM
STAT- MEDLINE
DCOM- 20230408
LR  - 20230408
IS  - 1876-4479 (Electronic)
IS  - 1873-9946 (Print)
IS  - 1873-9946 (Linking)
VI  - 17
IP  - 3
DP  - 2023 Apr 3
TI  - Tofacitinib for the Treatment of Ulcerative Colitis: An Integrated Summary of up 
      to 7.8 Years of Safety Data from the Global Clinical Programme.
PG  - 338-351
LID - 10.1093/ecco-jcc/jjac141 [doi]
AB  - BACKGROUND AND AIMS: Tofacitinib is an oral small molecule Janus kinase [JAK] 
      inhibitor for the treatment of ulcerative colitis. We report an integrated 
      summary of tofacitinib safety [exposure: </=7.8 years] from the global clinical 
      programme. METHODS: Patients receiving tofacitinib 5 or 10 mg twice daily [BID] 
      from completed phase [P]2/3 placebo-controlled studies, an open-label, long-term 
      extension study [final data cut-off: August 24, 2020], and interim analysis of a 
      P3b/4 study (interim data cut-off: February 20, 2020; Overall plus P3b/4 [2020] 
      Cohort) were included. Proportions with adverse events [AEs] and serious AEs, and 
      incidence rates [IRs; unique patients with events/100 patient-years] for deaths 
      and AEs of special interest [AESI] were evaluated. Opportunistic infections, 
      malignancies, major adverse cardiovascular events [MACE] and gastrointestinal 
      perforations were adjudicated. RESULTS: In total, 1157 patients received one or 
      more dose of tofacitinib (mean duration: 946.9 days); 955/1157 [83%] received a 
      predominant dose of 10 mg BID; 412/1157 [35.6%] received tofacitinib for >4 
      years; 992/1157 [85.7%] had AEs, 244/1157 [21.1%] had serious AEs and 134/1157 
      (11.6%) discontinued use due to AEs. IRs [95% confidence intervals] for all 
      tofacitinib doses were: deaths, 0.23 [0.09-0.46]; serious infections, 1.69 
      [1.26-2.21]; herpes zoster [non-serious and serious], 3.30 [2.67-4.04]; 
      opportunistic infections, 1.03 [0.70-1.46]; malignancies (excluding non-melanoma 
      skin cancer [NMSC]), 0.84 [0.55-1.24]; NMSC, 0.73 [0.45-1.10]; MACE, 0.29 
      [0.13-0.55]; deep vein thrombosis, 0.03 [0.00-0.18]; pulmonary embolism, 0.19 
      [0.07-0.42]; gastrointestinal perforations, 0.10 [0.02-0.28]. CONCLUSIONS: AESI 
      IRs were stable to 7.8 years and generally <2.0 in the Overall plus P3b/4 [2020] 
      Cohort, with the exception of herpes zoster [a known risk of tofacitinib 
      treatment]. 
      ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304JCC 
      Topic/keyword selection: 3. Clinical trials.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of European 
      Crohn's and Colitis Organisation.
FAU - Sandborn, William J
AU  - Sandborn WJ
AD  - Division of Gastroenterology, University of California San Diego, La Jolla, CA, 
      USA.
FAU - D'Haens, Geert R
AU  - D'Haens GR
AD  - Department of Gastroenterology, Amsterdam University Medical Centres, Amsterdam, 
      The Netherlands.
FAU - Sands, Bruce E
AU  - Sands BE
AD  - Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at 
      Mount Sinai, New York, NY, USA.
FAU - Panaccione, Remo
AU  - Panaccione R
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, University 
      of Calgary, Calgary, AB, Canada.
FAU - Ng, Siew C
AU  - Ng SC
AD  - Institute of Digestive Disease, Department of Medicine and Therapeutics, LKS 
      Institute of Health Science, Chinese University of Hong Kong, Hong Kong.
FAU - Lawendy, Nervin
AU  - Lawendy N
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Kulisek, Nicole
AU  - Kulisek N
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Modesto, Irene
AU  - Modesto I
AD  - Pfizer Inc, New York, NY, USA.
FAU - Guo, Xiang
AU  - Guo X
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Mundayat, Rajiv
AU  - Mundayat R
AD  - Pfizer Inc, New York, NY, USA.
FAU - Su, Chinyu
AU  - Su C
AD  - Pfizer Inc, Collegeville, PA, USA.
FAU - Vranic, Ivana
AU  - Vranic I
AD  - Pfizer Ltd, Tadworth, Surrey, UK.
FAU - Panes, Julian
AU  - Panes J
AD  - Department of Gastroenterology, Hospital Clinic de Barcelona, IDIBAPS, CIBERehd, 
      Barcelona, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT01458574
SI  - ClinicalTrials.gov/NCT03281304
SI  - ClinicalTrials.gov/NCT00787202
SI  - ClinicalTrials.gov/NCT01465763
SI  - ClinicalTrials.gov/NCT01470612
SI  - ClinicalTrials.gov/NCT01458951
GR  - Pfizer/
PT  - Clinical Trial
PT  - Journal Article
PL  - England
TA  - J Crohns Colitis
JT  - Journal of Crohn's & colitis
JID - 101318676
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 87LA6FU830 (tofacitinib)
SB  - IM
EIN - J Crohns Colitis. 2022 Dec 29;:. PMID: 36579949
MH  - Humans
MH  - *Colitis, Ulcerative/complications
MH  - *Herpes Zoster/chemically induced/epidemiology
MH  - *Janus Kinase Inhibitors/adverse effects
MH  - *Opportunistic Infections/epidemiology
MH  - Protein Kinase Inhibitors/adverse effects
MH  - Pyrroles/adverse effects
MH  - *Skin Neoplasms
MH  - Treatment Outcome
PMC - PMC10069618
OTO - NOTNLM
OT  - Ulcerative colitis
OT  - safety
OT  - tofacitinib
COIS- WJS has received research grants from AbbVie, Abivax, Arena Pharmaceuticals, 
      Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, 
      Janssen, Eli Lilly, Pfizer Inc, Prometheus Biosciences, Seres Therapeutics, 
      Shire, Takeda and Theravance Biopharma; consulting fees from AbbVie, Abivax, 
      Admirx, Alfasigma, Alimentiv [previously Robarts Clinical Trials, owned by 
      Alimentiv Health Trust], Alivio Therapeutics, Allakos, Amgen, Applied Molecular 
      Transport, Arena Pharmaceuticals, Bausch Health [Salix], Beigene, Bellatrix 
      Pharmaceuticals, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers 
      Squibb, Celgene, Celltrion, Cellularity, Cosmo Pharmaceuticals, Escalier 
      Biosciences, Equillium, Forbion, Genentech/Roche, Gilead Sciences, Glenmark 
      Pharmaceuticals, Gossamer Bio, Immunic [Vital Therapies], Index Pharmaceuticals, 
      Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Eli Lilly, 
      Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer Inc, Progenity, Prometheus 
      Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, 
      Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, 
      Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance 
      Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vendata Biosciences, 
      Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon 
      Biosciences and Zealand Pharma; is a shareholder of Allakos, BeiGene, Gossamer 
      Bio, Oppilan Pharma, Prometheus Biosciences, Prometheus Laboratories Progenity, 
      Shoreline Biosciences, Ventyx Biosciences, Vimalan Biosciences and Vivreon 
      Biosciences; and is an employee of Shoreline Biosciences. GRD'H has been an 
      advisor for AbbVie, Ablynx, Amakem, AM Pharma, Avaxia, Biogen, Bristol-Myers 
      Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmo, Covidien, Dr. Falk 
      Pharma, Engene, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, 
      GlaxoSmithKline, Hospira, Johnson & Johnson, Medimetrics, Millennium/Takeda, 
      Mitsubishi Pharma, MSD, Mundipharma, Novo Nordisk, Pfizer Inc, Prometheus 
      Laboratories/Nestle, Receptos, Robarts Clinical Trials, Salix, Sandoz, Setpoint, 
      Shire, Teva, TiGenix, Tillotts, Topivert, Versant and Vifor; and has received 
      speaker fees from AbbVie, Ferring Pharmaceuticals, Johnson & Johnson, 
      Millennium/Takeda, MSD, Mundipharma, Norgine, Pfizer Inc, Shire, Tillotts and 
      Vifor. BES has received research grants from Arena Pharmaceuticals, Celgene, 
      Theravance Biopharma R&D and personal fees from 4D Pharma, AbbVie, Allergan, 
      Amgen, Abivax, Arena Pharmaceuticals, AstraZeneca, Baxalta Bioscience India, 
      Boehringer-Ingelheim, Boston Pharmaceuticals, Capella Bioscience, Celgene, 
      Celltrion Healthcare, Ferring Pharmaceuticals, Genentech, Gilead Sciences, 
      GlaxoSmithKline, Hoffmann-La Roche, Immunic, InDex Pharmaceuticals, Inotrem, 
      Ironwood Pharmaceuticals, Janssen, Johnson & Johnson, Kallyope, Eli Lilly, 
      Morphic Therapeutic, Oppilan Pharma, OSE Immunotherapeutics, Otsuka, Palatin 
      Technologies, Pfizer Inc, Progenity, Prometheus Biosciences IBD, Prometheus 
      Laboratories, Protagonist Therapeutics, Redhill Biopharma, Rheos Medicines, Salix 
      Pharmaceuticals, Seres Therapeutics, Shire, Sienna Biopharmaceuticals, Surrozen, 
      Takeda, TARGET RWE, Theravance Biopharma R&D, USWM Enterprises, Viela Bio, 
      Vivelix Pharmaceuticals, Ventyx Biosciences and is a shareholder of Ventyx 
      Biosciences and Vivante Health; and gets non-financial support from Eli Lilly, 
      Pfizer Inc and Takeda. RP has received consulting fees from AI4GI, AbbVie, Amgen, 
      Arena Pharmaceuticals, Atlantic Healthcare, BioBalance, Boehringer Ingelheim, 
      Bristol-Myers Squibb, Celgene, Coronado Biosciences, Cosmo Technologies, Eagle, 
      Eisai Medical Research, Elan, Eli Lilly, EnGene, Ferring Pharmaceuticals, 
      Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Innomar, Janssen, 
      Lycera, Meda, Merck & Co., Merck Research Laboratories, Novo Nordisk, PDL 
      Biopharma, Pfizer Inc, Prometheus Laboratories, Protagonist, Receptos, Robarts 
      Clinical Trials, Sandoz, Sanofi Genzyme, Satisfai Health, Shire, Sigmoid Pharma, 
      Specialty Rx, Sublimity, Takeda and TherAdvance; and has acted as a reviewer for 
      AI4GI, AbbVie, Amgen, Arena Pharmaceuticals, Atlantic Healthcare, BioBalance, 
      Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coronado Biosciences, Cosmo 
      Technologies, Eagle, Eisai Medical Research, Elan, Eli Lilly, EnGene, Ferring 
      Pharmaceuticals, Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, 
      Innomar, Janssen, Lycera, Meda, Merck & Co., Merck Research Laboratories, Novo 
      Nordisk, PDL Biopharma, Pfizer Inc, Prometheus Laboratories, Protagonist, 
      Receptos, Robarts Clinical Trials, Sandoz, Sanofi Genzyme, Satisfai Health, 
      Shire, Sigmoid Pharma, Specialty Rx, Sublimity, Takeda and TherAdvance. SCN has 
      received research grants from AbbVie, Ferring Pharmaceuticals, and Olympus; 
      speakers fees from AbbVie, Ferring Pharmaceuticals, Janssen, Menarini, Takeda, 
      Tillotts and Pfizer Inc; is a scientific co-founder of GenieBiome Ltd; and is a 
      director of Microbiota I Center. NL, NK, IM, XG, RM, CS and IV are employees and 
      shareholders of Pfizer Inc. JP has received research grants from AbbVie and 
      Pfizer Inc; and personal fees from AbbVie, Arena, Athos, Boehringer Ingelheim, 
      Celgene, Celltrion, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, 
      GlaxoSmithKline, Immunic, Janssen, Mirum, Morphic, Nestle, Origo, Pandion, Pfizer 
      Inc, Progenity, Takeda, Theravance Biopharma and Wassermann.
EDAT- 2022/09/21 06:00
MHDA- 2023/04/05 06:42
PMCR- 2022/09/17
CRDT- 2022/09/20 04:43
PHST- 2023/04/05 06:42 [medline]
PHST- 2022/09/21 06:00 [pubmed]
PHST- 2022/09/20 04:43 [entrez]
PHST- 2022/09/17 00:00 [pmc-release]
AID - 6702643 [pii]
AID - jjac141 [pii]
AID - 10.1093/ecco-jcc/jjac141 [doi]
PST - ppublish
SO  - J Crohns Colitis. 2023 Apr 3;17(3):338-351. doi: 10.1093/ecco-jcc/jjac141.