William J Sandborn1, Laurent Peyrin-Biroulet2, Daniel Quirk3, Wenjin Wang3, Chudy I Nduaka3, Arnab Mukherjee4, Chinyu Su3, Bruce E Sands5. 1. Division of Gastroenterology, University of California, San Diego, La Jolla, California. 2. Inserm U1256 and Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandœuvre lès-Nancy, France. 3. Pfizer Inc, Collegeville, Pennsylvania. 4. Pfizer Inc, Groton, Connecticut. 5. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: bruce.sands@mssm.edu.
Abstract
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.
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.
Authors: Remo Panaccione; Maria T Abreu; Irina Lazariciu; Rajiv Mundayat; Nervin Lawendy; Leonardo Salese; John C Woolcott; Bruce E Sands; María Chaparro Journal: Aliment Pharmacol Ther Date: 2022-03-05 Impact factor: 9.524