TY - JOUR
T1 - Efficacy and Safety of Extended Induction With Tofacitinib for the Treatment of Ulcerative Colitis
AU - Sandborn, William J.
AU - Peyrin-Biroulet, Laurent
AU - Quirk, Daniel
AU - Wang, Wenjin
AU - Nduaka, Chudy I.
AU - Mukherjee, Arnab
AU - Su, Chinyu
AU - Sands, Bruce E.
N1 - Funding Information:
Data in this manuscript were previously presented at the 82nd Annual Scientific Meeting of the American College of Gastroenterology (2017), Digestive Disease Week (2018 and 2019), and the 13th–15th Congresses of the European Crohn's and Colitis Organisation (2018–2020). Medical writing support, under the guidance of the authors, was provided by Helen Findlow, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). The authors thank the patients, investigators, and trial teams who were involved in the tofacitinib UC clinical program. William J. Sandborn (Writing – original draft: Equal; Writing – review & editing: Equal; interpreted the data: Equal), Laurent Peyrin-Biroulet (Writing – original draft: Equal; Writing – review & editing: Equal; interpreted the data: Equal), Daniel Quirk (Writing – original draft: Equal; Writing – review & editing: Equal; design of the analysis and interpreted the data: Equal), Wenjin Wang (Writing – original draft: Equal; Writing – review & editing: Equal; design of the analysis and interpreted the data: Equal), Chudy I. Nduaka (Writing – original draft: Equal; Writing – review & editing: Equal; design of the analysis and interpreted the data: Equal), Arnab Mukherjee (Writing – original draft: Equal; Writing – review & editing: Equal; design of the analysis and interpreted the data: Equal), Chinyu Su (Writing – original draft: Equal; Writing – review & editing: Equal; design of the analysis and interpreted the data: Equal), Bruce E. Sands (Writing – original draft: Equal; Writing – review & editing: Equal; interpreted the data: Equal) Conflicts of interest These authors disclose the following: William J. Sandborn has received research grants from AbbVie, Amgen, Atlantic Healthcare Limited, Celgene/Receptos, Genentech, Gilead Sciences, Janssen, Lilly, Pfizer Inc, Prometheus Laboratories (now Prometheus Biosciences), and Takeda; consulting fees from AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Avexegen Therapeutics, BeiGene, Boehringer Ingelheim, Celgene, Celltrion, Conatus, Cosmo, Escalier Biosciences, Ferring, Forbion, Genentech, Gilead Sciences, Gossamer Bio, Incyte, Janssen, Kyowa Kirin Pharmaceuticals, Landos Biopharma, Lilly, Oppilan Pharma, Otsuka, Pfizer Inc, Prometheus Laboratories, Reistone, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Series Therapeutics, Shire, Sienna Biopharmaceuticals, Sigmoid Biotechnologies, Sterna Biologicals, Sublimity Therapeutics, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma, UCB Pharma, Ventyx Biosciences, Vimalan Biosciences, and Vivelix Pharmaceuticals; and stock or stock options from BeiGene, Escalier Biosciences, Gossamer Bio, Oppilan Pharma, Prometheus Biosciences, Ritter Pharmaceuticals, Ventyx Biosciences, and Vimalan Biosciences. Laurent Peyrin-Biroulet has received lecture fees from AbbVie, Amgen, Biogen, Celltrion, Ferring, Janssen, Merck, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts; and consulting fees from AbbVie, Alma, Amgen, Biogaran, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Enterome, Ferring, Genentech, Index Pharmaceuticals, Janssen, Lilly, Merck, Nestlé, Pfizer Inc, Samsung Bioepis, Sandoz, Sterna, Takeda, Tillotts, and Vifor Pharmacosmos. Daniel Quirk, Wenjin Wang, Chudy I. Nduaka, Arnab Mukherjee, and Chinyu Su are employees and stockholders of Pfizer Inc. Bruce E. Sands has received consulting fees and research grants from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Pfizer Inc, and Takeda; and consulting fees from 4D Pharma, Akros Pharma, Allergan, Arena Pharmaceuticals, Boehringer Ingelheim, Capella Biosciences, EnGene, Ferring, Forward Pharma, Gilead, Immune Pharmaceuticals, Lilly, Lyndra, MedImmune, Oppilan Pharma, Otsuka, Palatin Technologies, Progenity, Receptos, Rheos Pharmaceuticals, Seres Therapeutics, Synergy Pharmaceuticals, Target PharmaSolutions, Theravance Biopharma R&D, TiGenix, TopiVert Pharma, UCB Pharma, Vedanta Biosciences, and Vivelix Pharmaceuticals. Funding These trials were sponsored by Pfizer Inc.
Funding Information:
Data in this manuscript were previously presented at the 82nd Annual Scientific Meeting of the American College of Gastroenterology (2017), Digestive Disease Week (2018 and 2019), and the 13th–15th Congresses of the European Crohn’s and Colitis Organisation (2018–2020). Medical writing support, under the guidance of the authors, was provided by Helen Findlow, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–464). The authors thank the patients, investigators, and trial teams who were involved in the tofacitinib UC clinical program.
Funding Information:
Funding These trials were sponsored by Pfizer Inc.
Publisher Copyright:
© 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - Background & Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in a dose-ranging phase 2 induction trial, 3 phase 3 randomized, placebo-controlled trials (OCTAVE Induction 1 and 2; and OCTAVE Sustain), and an ongoing, open-label, long-term extension trial (OCTAVE Open) in patients with moderately to severely active UC. Here, we assessed short- and long-term efficacy and safety of extended induction (16 weeks) with tofacitinib 10 mg twice daily (BID) in patients who failed to respond to initial induction (8 weeks) treatment. Methods: In patients who achieved a clinical response following extended induction (delayed responders), the efficacy and safety of tofacitinib were evaluated up to Month 36 of OCTAVE Open. Results: 52.2% of patients who did not achieve clinical response to 8 weeks’ treatment with tofacitinib 10 mg BID in the induction studies achieved a clinical response following extended induction (delayed responders). At Month 12 of OCTAVE Open, 70.3%, 56.8%, and 44.6% of delayed responders maintained clinical response and achieved endoscopic improvement and remission, respectively. Corresponding values at Month 36 were 56.1%, 52.0%, and 44.6%. The safety profile of the subsequent 8 weeks was similar to the initial 8 weeks. Conclusions: Overall, the majority of patients achieved a clinical response after 8 or 16 weeks’ induction therapy with tofacitinib 10 mg BID. Tofacitinib 10 mg BID, administered as induction therapy for up to 16 weeks, had a comparable safety profile to 8 weeks’ induction therapy. Most delayed responders at Month 36 were in remission. ClinicalTrials.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01470612.
AB - Background & Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in a dose-ranging phase 2 induction trial, 3 phase 3 randomized, placebo-controlled trials (OCTAVE Induction 1 and 2; and OCTAVE Sustain), and an ongoing, open-label, long-term extension trial (OCTAVE Open) in patients with moderately to severely active UC. Here, we assessed short- and long-term efficacy and safety of extended induction (16 weeks) with tofacitinib 10 mg twice daily (BID) in patients who failed to respond to initial induction (8 weeks) treatment. Methods: In patients who achieved a clinical response following extended induction (delayed responders), the efficacy and safety of tofacitinib were evaluated up to Month 36 of OCTAVE Open. Results: 52.2% of patients who did not achieve clinical response to 8 weeks’ treatment with tofacitinib 10 mg BID in the induction studies achieved a clinical response following extended induction (delayed responders). At Month 12 of OCTAVE Open, 70.3%, 56.8%, and 44.6% of delayed responders maintained clinical response and achieved endoscopic improvement and remission, respectively. Corresponding values at Month 36 were 56.1%, 52.0%, and 44.6%. The safety profile of the subsequent 8 weeks was similar to the initial 8 weeks. Conclusions: Overall, the majority of patients achieved a clinical response after 8 or 16 weeks’ induction therapy with tofacitinib 10 mg BID. Tofacitinib 10 mg BID, administered as induction therapy for up to 16 weeks, had a comparable safety profile to 8 weeks’ induction therapy. Most delayed responders at Month 36 were in remission. ClinicalTrials.gov: NCT00787202; NCT01465763; NCT01458951; and NCT01470612.
KW - Induction Therapy
KW - Inflammatory Bowel Disease
KW - Janus Kinase Inhibitor
KW - OCTAVE
UR - http://www.scopus.com/inward/record.url?scp=85107416802&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2020.10.038
DO - 10.1016/j.cgh.2020.10.038
M3 - Article
C2 - 33127596
AN - SCOPUS:85107416802
SN - 1542-3565
VL - 20
SP - 1821-1830.e3
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 8
ER -