TY - JOUR
T1 - Safety and efficacy of tofacitinib for treatment of ulcerative colitis
T2 - final analysis of OCTAVE Open, an open-label, long-term extension study with up to 7.0 years of treatment
AU - Sandborn, William J.
AU - Lawendy, Nervin
AU - Danese, Silvio
AU - Su, Chinyu
AU - Loftus, Edward V
AU - Hart, Ailsa
AU - Dotan, Iris
AU - Damião, Adérson O.M.C.
AU - Judd, Donna T
AU - Guo, Xiang
AU - Modesto, Irene
AU - Wang, Wenjin
AU - Panés, Julian
N1 - Funding Information:
OCTAVE Open was sponsored by Pfizer Inc. Medical writing support, under the guidance of the authors, was provided by Chris Guise, PhD, of CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines ( 2015;163:461–464). Ann Intern Med
Funding Information:
WJ Sandborn has received grant support, personal fees and non‐financial support from Pfizer Inc during the conduct of the study; research support from AbbVie, Abivax, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Pfizer Inc, Prometheus Biosciences, Seres Therapeutics, Shire, Takeda and Theravance Biopharma; consultancy fees from AbbVie, Abivax, AdMIRx, Alfasigma, Alimentiv (Robarts Clinical Trials, owned by Health Academic Research Trust [HART]), 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, Equillium, Escalier Biosciences, Forbion, Genentech/Roche, Gilead Sciences, Glenmark Pharmaceuticals, Gossamer Bio, Immunic (Vital Therapies), Index Pharmaceuticals, Intact Therapeutics, Janssen, Kyverna Therapeutics, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pandion Therapeutics, Pfizer Inc, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Provention Bio, Reistone Biopharma, Seres Therapeutics, Shanghai Pharma Biotherapeutics, Shire, Shoreline Biosciences, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vedanta Biosciences, Ventyx Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vivreon Biosciences and Zealand Pharma; and has stock or stock options in Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Progenity, Prometheus Biosciences, Shoreline Biosciences, Ventyx Biosciences and Vimalan Biosciences. WJ Sandborn’s spouse has received consultancy fees from Iveric Bio and Oppilan Pharma; is an employee of Prometheus Biosciences; and has stock or stock options in Iveric Bio, Oppilan Pharma Progenity, Prometheus Biosciences, Ventyx Biosciences and Vimalan Biosciences. N Lawendy, C Su, DT Judd, X Guo, I Modesto and W Wang are all employees and stockholders of Pfizer Inc. S Danese has received consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead Sciences, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB and Vifor. EV Loftus Jr. has received research support from AbbVie, Amgen, Bristol‐Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer Inc, Receptos, Robarts Clinical Trials, Takeda, Theravance and UCB; and consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol‐Myers Squibb, Boehringer Ingelheim, Calibr, Celgene, Lilly, Genentech, Gilead Sciences, Gossamer Bio, Iterative Scopes, Janssen, Lilly, Ono Pharma, Pfizer Inc, Sun Pharma, Takeda and UCB. A Hart has received consultancy fees from AbbVie, Allergan, Atlantic, Bristol‐Myers Squibb, Celltrion, Falk Pharma, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer Inc, Pharmacosmos, Shire and Takeda; lecture fees from AbbVie, Atlantic, Bristol‐Myers Squibb, Celltrion, Falk Pharma, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer Inc, Pharmacosmos, Shire and Takeda; other fees from Genentech (Global Steering Committee); and has served as an advisory board member for AbbVie, Atlantic, Bristol‐Myers Squibb, Celltrion, Falk Pharma, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer Inc, Pharmacosmos, Shire and Takeda. I Dotan has received personal fees from AbbVie, Abbott, Altman Research, Arena Pharmaceuticals, Athos, Cambridge Healthcare, Celgene/Bristol‐Myers Squibb, Celltrion, DSM, Falk Pharma, Ferring, Food Industries Organisation, Genentech/Roche, Gilead Sciences, Janssen, MSD, Neopharm, Nestlé, Pfizer Inc, Rafa Laboratories, Sandoz, Sangamo, Sublimity, Takeda and Wildbio. AOMC Damião has received personal fees from AbbVie, Ferring, Janssen, Takeda and Pfizer Inc. J Panés has received research support from AbbVie and Pfizer Inc; and personal fees from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltrion, F. Hoffmann‐La Roche, Genentech, Gilead Sciences, GlaxoSmithKline, Immunic, Janssen, Origo, Pandion, Pfizer Inc, Progenity, Robarts Clinical Trials, Takeda, Theravance and Wassermann. Declaration of personal interests:
Funding Information:
OCTAVE Open was sponsored by Pfizer Inc. Medical writing support, under the guidance of the authors, was provided by Chris Guise, PhD, of CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). The authors thank the patients, physicians and trial team involved in OCTAVE Open. Medical writing support, under the guidance of the authors, was provided by Chris Guise, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). William J. Sandborn is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases-funded San Diego Digestive Diseases Research Center (P30 DK120515).
Funding Information:
The authors thank the patients, physicians and trial team involved in OCTAVE Open. Medical writing support, under the guidance of the authors, was provided by Chris Guise, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, USA in accordance with Good Publication Practice (GPP3) guidelines ( 2015;163:461–464). William J. Sandborn is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases‐funded San Diego Digestive Diseases Research Center (P30 DK120515). All authors approved the final version of the article, including the authorship list. Ann Intern Med
Publisher Copyright:
© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2022/2
Y1 - 2022/2
N2 - Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study. Aims: The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective. Methods: Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit). Results: In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively. Conclusion: Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.
AB - Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present final data from OCTAVE Open, an open-label, long-term extension study. Aims: The primary objective of OCTAVE Open was to assess the safety and tolerability of long-term tofacitinib in patients with ulcerative colitis; evaluating efficacy was a secondary objective. Methods: Eligible patients included OCTAVE Induction 1&2 non-responders and OCTAVE Sustain completers/treatment failures. Patients in remission at OCTAVE Open baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. Incidence rates (unique patients with events/100 patient-years) for adverse events of special interest were calculated; ≤7.0 years of observation. Efficacy endpoints derived from Mayo score were reported ≤36 months (last scheduled endoscopy visit). Results: In OCTAVE Open, 769 of 944 patients (81.5%) initially received tofacitinib 10 mg b.d. Among all patients (2440.8 patient-years of exposure), incidence rates (IRs; 95% confidence intervals) for deaths and adverse events of special interest were: deaths, 0.25 (0.09-0.54); serious infections, 1.61 (1.14-2.20); herpes zoster (non-serious and serious), 3.16 (2.47-3.97); opportunistic infections, 0.87 (0.54-1.33); major adverse cardiovascular events, 0.16 (0.04-0.42); malignancies (excluding non-melanoma skin cancer), 1.03 (0.67-1.52); non-melanoma skin cancer, 0.75 (0.45-1.19); deep vein thrombosis, 0.04 (0.00-0.23); pulmonary embolism, 0.21 (0.07-0.48). At Month 36, 66.9% and 40.3% showed clinical response, 64.6% and 37.1% had endoscopic improvement, and 58.9% and 33.7% maintained or achieved remission, with tofacitinib 5 and 10 mg b.d. respectively. Conclusion: Tofacitinib demonstrated consistent safety up to 7.0 years. Data collected up to Month 36 support long-term efficacy beyond the 52-week maintenance study.
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U2 - 10.1111/apt.16712
DO - 10.1111/apt.16712
M3 - Article
C2 - 34854095
AN - SCOPUS:85120378591
SN - 0269-2813
VL - 55
SP - 464
EP - 478
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 4
ER -