Presence of risk factors associated with colectomy among patients with ulcerative colitis: a post hoc analysis of data from the tofacitinib OCTAVE ulcerative colitis clinical program

David T Rubin; Leonardo Salese; Mitchell Cohen; Paulo G Kotze; John C Woolcott; Chinyu Su; Rajiv Mundayat; Jerome Paulissen; Joana Torres; Millie D Long

doi:10.1177/17562848231189122

Presence of risk factors associated with colectomy among patients with ulcerative colitis: a post hoc analysis of data from the tofacitinib OCTAVE ulcerative colitis clinical program

Therap Adv Gastroenterol. 2023 Aug 7:16:17562848231189122. doi: 10.1177/17562848231189122. eCollection 2023.

Authors

David T Rubin¹, Leonardo Salese², Mitchell Cohen³, Paulo G Kotze⁴, John C Woolcott⁵, Chinyu Su⁵, Rajiv Mundayat⁶, Jerome Paulissen⁶, Joana Torres^{7

8

9}, Millie D Long¹⁰

Affiliations

¹ University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA.
² Pfizer Inc, Collegeville, PA, USA Former employee of Pfizre.
³ Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, USA.
⁴ IBD Outpatient Clinics, Colorectal Surgery Unit, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.
⁵ Pfizer Inc, Collegeville, PA, USA.
⁶ Pfizer Inc, New York, NY, USA.
⁷ Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal.
⁸ Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal.
⁹ Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
¹⁰ Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.

Abstract

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC).

Objective: To assess colectomy incidence rates (IRs) and baseline characteristics for the presence of identified colectomy risk factors among patients in the tofacitinib OCTAVE UC clinical program.

Design: This post hoc analysis evaluated patients in the 8-week OCTAVE Induction 1 and 2, 52-week OCTAVE Sustain, and OCTAVE Open (open-label, long-term extension) studies.

Methods: IRs [95% confidence interval (CI)] for colectomy were analyzed. Baseline risk factors based on clinical guidelines: aged <40 years at diagnosis, extensive colitis, severe endoscopic disease [Mayo endoscopic subscore (MES) = 3], hospitalization for UC within 12 months, C-reactive protein (CRP) >3 mg/L, and serum albumin <3.5 g/dL. Baseline risk factors were evaluated in patients who underwent colectomy by study and summarized descriptively.

Results: Over a maximum of 7.8 years of tofacitinib exposure, 14 patients underwent colectomy: 3/1139 (0.3%) in OCTAVE Induction 1 and 2 [tofacitinib 10 mg twice daily (BID): n = 2; placebo: n = 1], 3/593 (0.5%) in OCTAVE Sustain (placebo: n = 3), and 8/944 (0.8%) in OCTAVE Open (tofacitinib 10 mg BID: n = 8). Colectomy IR per 100 patient-years for all patients who received ⩾1 tofacitinib dose was 0.34 (95% CI: 0.16-0.63). All patients who underwent colectomy had ⩾1 risk factor and prior tumor necrosis factor inhibitor (TNFi) failure, among which the most common risk factors were a MES of 3 (n = 13), CRP >3 mg/L (n = 11), and aged <40 years at diagnosis (n = 9).

Conclusions: Among patients with moderate to severe UC receiving tofacitinib, colectomies were infrequent; all patients undergoing colectomy had prior TNFi failure, and most had multiple additional risk factors. This provides important information to discuss with patients and inform management decisions.

Registration: NCT01465763; NCT01458951; NCT01458574; and NCT01470612.

Keywords: colectomy; tofacitinib; ulcerative colitis.

Associated data

ClinicalTrials.gov/NCT01458574
ClinicalTrials.gov/NCT01465763
ClinicalTrials.gov/NCT01470612
ClinicalTrials.gov/NCT01458951