Clin Gastroenterol Hepatol. 2022 Mar;20(3):591-601.e8.doi: 10.1016/j.cgh.2021.02.043. Epub 2021 Mar 6.

William J Sandborn ¹, Laurent Peyrin-Biroulet ², Ala I Sharara ³, Chinyu Su ⁴, Irene Modesto ⁵, Rajiv Mundayat ⁵, L Mert Gunay ⁶, Leonardo Salese ⁴, Bruce E Sands ⁷

Author information

¹Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: wsandborn@health.ucsd.edu.

²Inserm Nutrition, Genetics, and Environmental Risk Exposure U1256, Department of Gastroenterology, Nancy University Hospital, Lorraine University, Vandœuvre lès-Nancy, France.

³Division of Gastroenterology, American University of Beirut Medical Center, Beirut, Lebanon.

⁴Pfizer Inc, Collegeville, Pennsylvania.

⁵Pfizer Inc, New York, New York.

⁶Pfizer Inc, Istanbul, Turkey.

⁷Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

Abstract

Background & aims: Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We summarize the efficacy and safety data of tofacitinib 5 or 10 mg twice daily in the UC clinical program, stratified by prior tumor necrosis factor inhibitor (TNFi) failure status.

Methods: Efficacy was assessed in the pooled phase 3 OCTAVE Induction 1 and 2 studies (N = 1139), the phase 3 OCTAVE Sustain maintenance study (N = 593), and the dose-escalation subpopulation of the open-label, long-term extension OCTAVE Open study (N = 59). Safety was assessed in OCTAVE Sustain, the dose-escalation subpopulation, and the Overall Cohort, which included patients from OCTAVE Induction 1 and 2, OCTAVE Sustain, and OCTAVE Open (N = 1124; no prior TNFi failure N = 541; prior TNFi failure N = 583; phase 2 data were excluded when stratified by prior TNFi failure status). The dose-escalation subpopulation received tofacitinib 10 mg twice daily in OCTAVE Induction 1 and 2, tofacitinib 5 mg twice daily in OCTAVE Sustain, and tofacitinib 10 mg twice daily in OCTAVE Open.

Results: Tofacitinib had greater efficacy than placebo, regardless of prior TNFi failure status. In OCTAVE Sustain and the Overall Cohort, herpes zoster [HZ] (nonserious and serious) rates were numerically higher in tofacitinib-treated patients with vs without prior TNFi failure. Dose escalation to tofacitinib 10 mg twice daily generally recaptured clinical response for most patients. HZ (nonserious and serious) rates were numerically higher in the dose-escalation subpopulation vs the Overall Cohort.

Conclusions: Tofacitinib was efficacious in patients with UC regardless of prior TNFi failure status. HZ (nonserious and serious) rates were numerically higher in patients who had previously failed TNFi. ClinicalTrials.gov: A3921063 (NCT00787202); OCTAVE Induction 1 (NCT01465763); OCTAVE Induction 2 (NCT01458951); OCTAVE Sustain (NCT01458574); and OCTAVE Open (NCT01470612).