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.
| Autor: | Rubin DT; University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA., Salese L; Pfizer Inc, Collegeville, PA, USA Former employee of Pfizre., Cohen M; Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, USA., Kotze PG; IBD Outpatient Clinics, Colorectal Surgery Unit, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil., Woolcott JC; Pfizer Inc, Collegeville, PA, USA., Su C; Pfizer Inc, Collegeville, PA, USA., Mundayat R; Pfizer Inc, New York, NY, USA., Paulissen J; Pfizer Inc, New York, NY, USA., Torres J; Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal.; Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal.; Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal., Long MD; Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Therapeutic advances in gastroenterology [Therap Adv Gastroenterol] 2023 Aug 07; Vol. 16, pp. 17562848231189122. Date of Electronic Publication: 2023 Aug 07 (Print Publication: 2023). |
| DOI: | 10.1177/17562848231189122 |
| Abstrakt: | 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. Competing Interests: The authors declare the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DTR has received consulting fees from AbbVie, AltruBio, Arena Pharmaceuticals, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corp/Syneos, Connect Biopharma, Eli Lilly, GalenPharma/Atlantica, Genentech/Roche, Gilead Sciences, InDex Pharmaceuticals, Iterative Scopes, Janssen, Pfizer Inc, Prometheus Biosciences, Reistone, Takeda, and Techlab Inc, and has received a research grant from Takeda. LS is a stockholder of Pfizer Inc and was an employee of Pfizer Inc at the time of this analysis. MC, JCW, CS, and RM are employees and stockholders of Pfizer Inc. PGK has received consulting and speaker fees from AbbVie, Janssen, Pfizer Inc, and Takeda, and has received research grants from Pfizer Inc and Takeda. JP is an employee of Syneos Health, which was a paid contractor to Pfizer in connection with the development of this article and related statistical analysis. JT has received advisory board fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Galapagos, Janssen, and Pfizer Inc, research grants from AbbVie and Janssen, and speaker fees from AbbVie, Galapagos, Janssen, and Pfizer Inc. MDL has received consulting fees from AbbVie, Bristol Myers Squibb, Calibr, Eli Lilly, Genentech, Janssen, Pfizer Inc, Prometheus Biosciences, Roche, Salix, Takeda, Target PharmaSolutions, Theravance, and Valeant, and has received research grants from Pfizer Inc and Takeda. (© The Author(s), 2023.) |
| Databáze: | MEDLINE |
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