Search

Background: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P) 1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability., Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients., Design: Data included patients from the Placebo-controlled UC cohort (phase II OASIS, and phase III ELEVATE UC 52 and ELEVATE UC 12 trials) receiving QD etrasimod (2 or 1 mg) or placebo., Methods: Proportions and incidence rates (IRs; the number of patients with a TEAE divided by the total exposure in patient-years (PYs), per 100 PY) of Headache, Pyrexia, Nausea and Dizziness TEAEs were reported. Changes in heart rate among patients with Dizziness TEAEs were also evaluated., Results: Among 943 patients (etrasimod 2 mg, N  = 577 (276.7 PY); etrasimod 1 mg, N  = 52 (11.4 PY); placebo, N  = 314 (115.1 PY)), 48, 34, 27 and 21 patients experienced events of Headache, Pyrexia, Nausea and Dizziness, respectively. All events were non-serious; one patient treated with etrasimod was discontinued due to a Pyrexia TEAE. Numerically, IRs of Headache and Dizziness TEAEs were higher, and Nausea slightly higher, with etrasimod versus placebo (13.45 vs 8.63 per 100 PY, 6.52 vs 1.69 and 7.18 vs 5.13 per 100 PY, respectively); IRs were similar for Pyrexia. The duration of most TEAEs was 1-10 days., Conclusion: In the etrasimod UC clinical programme, all Headache, Pyrexia, Nausea and Dizziness events were non-serious. Headache and Dizziness were more frequent, and Nausea slightly more frequent, among patients receiving etrasimod versus placebo. The post hoc nature of this analysis is a limitation. These results reiterate the favourable safety profile and tolerability of etrasimod., Trial Registration: ClinicalTrials.gov: NCT02447302; NCT03945188; NCT03996369., Competing Interests: C.W.L. has received speaker fees from AbbVie, Dr Falk, Ferring, Hospira, Janssen, MSD, Pfizer Inc., Shire, Takeda and Warner-Chilcott; has receiving consultant fees from AbbVie, Dr Falk, Gilead, GSK, Hospira, Iterative Scopes, Janssen, MSD, Oshi Health, Pfizer Inc., Pharmacosmos, Takeda, Topivert, Trellus Health and Vifor Pharma and has received research funding from AbbVie and Gilead. J.T. has received advisory board fees from AbbVie, Bristol-Myers Squibb, Janssen and Pfizer Inc.; has received research grants from AbbVie and Janssen and has received speaker fees from AbbVie, Galapagos, Janssen and Pfizer Inc. Y.L. has served on advisory committee/as a board member for AbbVie, Celltrion, Eli Lilly, Janssen, Pfizer Inc., Sandoz, Takeda and has acted as a consultant for AbbVie, Eli Lilly, Janssen, Pfizer Inc. and Takeda. S.V. has received research grants from AbbVie, Galapagos, J&J, Pfizer and Takeda and has received speakers’ and/or consultancy fees from AbbVie, Abivax, AbolerISPharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, Mestag Therapeutics, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer Inc., Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Surrozen, Takeda, Theravance, Tillotts Pharma AG, VectivBio, Ventyx and Zealand Pharma. M.F., I.M., A.M., K.L., M.K. and J.W. are employees and shareholders of Pfizer Inc. M.G. is an employee and shareholder of Pfizer AG. E.V.L. has received consulting fees from AbbVie, Alvotech, Amgen, Arena, Astellas, Avalo Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion Healthcare, Eli Lilly Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iota Biosciences, Iterative Health, Janssen, KSL Diagnostics, Morphic Therapeutic, Ono Pharma, Protagonist, Scipher Medicine, Sun Pharma, Surrozen, Takeda, TR1X and UCB Pharma; has received research support from AbbVie, AstraZeneca, Bristol-Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer Inc., Takeda, Theravance and UCB Pharma and is a shareholder of Exact Sciences., (© The Author(s), 2024.)

Background: Long-term vedolizumab (VDZ) outcomes in real-world cohorts have been largely limited to 1-year follow-up, with few bio-naïve patients or objective markers of inflammation assessed., Objectives: We aimed to assess factors affecting VDZ persistence including clinical, biochemical and faecal biomarker remission at 1, 3 and 5 years., Design: We performed a retrospective, observational, cohort study., Methods: All adult inflammatory bowel disease (IBD) patients who had received VDZ induction for ulcerative colitis (UC)/IBD-unclassified (IBDU) were included. Baseline phenotype and follow-up data were collected via a review of electronic medical records., Results: We included 290 patients [UC n  = 271 (93.4%), IBDU n  = 19 (6.6%)] with a median time on VDZ of 27.6 months (interquartile range: 14.4-43.2). At the end of follow-up, a total of 157/290 (54.1%) patients remained on VDZ. The median time to discontinuation was 14.1 months (7.0-23.3). Previous exposure to ⩾1 advanced therapy, steroid use at baseline and disease extension (E3 and E2 versus E1) were independent predictors for worse VDZ persistence. Clinical remission (partial Mayo < 2) was 75.7% (171/226), 72.4% (157/217) and 70.2% (127/181) at years 1, 3 and 5, respectively. Steroid use during maintenance VDZ therapy occurred in 31.7% (92/290), hospitalization in 15.5% (45/290) and surgery in 3.4% (10/291). The rate of serious adverse events was 1.2 per 100 patient-years of follow-up., Conclusion: VDZ effectiveness appears enduring with favourable long-term safety profile. VDZ persistence was influenced by previous exposure to biologics/small molecules, disease distribution and steroid use at baseline in our study., Competing Interests: BG has served as acted as consultant to Galapagos and Abbvie and as speaker for Abbvie, Jansen, Takeda, Pfizer and Galapagos. NP has served as a speaker for Janssen, Takeda and Pfizer. Professor CWL has acted as a consultant to Abbvie, Janssen, Takeda, Pfizer, Galapagos, Bristol Myers Squibb, B.I., Sandoz, Novartis, GSK, Gilead, ViforPharma, Dr Falk, Trellus Health and Iterative Scopes; he has received speaking fees and travel support from Pfizer, Janssen, Abbvie, Galapagos, MSD, Takeda, Shire, Ferring, Hospira and Dr Falk. G-RJ has served as a speaker for Takeda, Janssen, Abbvie, Fresnius and Ferring. LAAPD has served on advisory board for Sandoz and Abbvie, and as a speaker for Janssen. CN has acted as a consultant to Galapagos. None of the other authors reported any conflicts of interest., (© The Author(s), 2024.)

Background and Aims: Tofacitinib is a Janus kinase inhibitor (JAKi) recently approved for the treatment of moderate to severe ulcerative colitis (UC) based on robust efficacy and safety data derived from OCTAVE clinical trials. Evidence on the outcomes of tofacitinib therapy in real-world UC patients is needed, as a number of these patients would be deemed ineligible for clinical trials. We have therefore summarised data derived from observational, real-world evidence (RWE) studies on the effectiveness and safety of tofacitinib in moderate to severe UC patients., Methods: We searched the PubMed, EMBASE, Scopus, Web of Science and Cochrane databases for observational studies on the use of tofacitinib in UC patients, published between 30 May 2018 and 24 January 2021. Pooled induction (8-14 weeks) and maintenance (16-26 weeks) clinical response and remission rates were calculated, as well as the proportion of reported adverse events using random effects models., Results: Nine studies were included, comprising 830 patients, of which 81% were previously treated with anti-tumour necrosis factor (TNF) and 57% with vedolizumab. Induction of clinical response and remission were achieved in 51% (95% confidence interval, 41-60%) and 37% (26-45%) of patients, after a median follow-up of 8 weeks. At the end of a median follow-up of 24 weeks, maintenance of clinical response and remission were met in 40% (31-50%) and 29% (23-36%) of patients, respectively. Thirty-two percent of the patients had at least one adverse event, the most commonly reported being mild infection (13%) and worsening of UC, requiring colectomy (13%). A third of the patients (35%) discontinued tofacitinib, most frequently due to primary non-response (51%)., Conclusion: Tofacitinib is a safe and effective therapy in real-world UC patients, as previously reported by clinical trials., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: L.A.L., none declared. N.C.-C., none declared. N.P. has received consultancy fees from Takeda, and speaker fees and/or travel support from Abbvie, Takeda and Norgine. S.S., none declared. L.A.A.P.D., none declared. G.-R.J., none declared. C.W.L. has received research support from Abbvie and Gilead; consultancy fees from Abbvie, Pfizer, Janssen, Gilead, Celltrion, Pharmacosmos, Takeda, Vifor, Iterative Scopes and Trellus Health; and speaker fees and/or travel support from Janssen, Abbvie, Pfizer, Dr Falk, Ferring, Hospira and Takeda., (© The Author(s), 2021.)

Introduction: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Outcome prediction based on early treatment response, along with clinical and laboratory variables, would be very useful for clinical practice. The aim of this study was to determine early variables predictive of responder status in patients with UC treated with tofacitinib., Methods: Data were collected from patients treated with tofacitinib 10 mg twice daily in the OCTAVE Induction 1 and 2 studies (NCT01465763 and NCT01458951). Logistic regression and random forest analyses were performed to determine the power of clinical and/or laboratory variables to predict 2- and 3-point partial Mayo score responder status of patients at Weeks 4 or 8 after baseline., Results: From a complete list of variables measured in OCTAVE Induction 1 and 2, analyses identified partial Mayo score, partial Mayo subscore (stool frequency, rectal bleeding, and Physician Global Assessment), cholesterol level, and C-reactive protein level as sufficient variables to predict responder status. Using these variables at baseline and Week 2 predicted responder status at Week 4 with 84-87% accuracy and Week 8 with 74-79% accuracy. Variables at baseline, Weeks 2 and 4 could predict responder status at Week 8 with 85-87% accuracy., Conclusion: Using a limited set of time-dependent variables, statistical and machine learning models enabled early and clinically meaningful predictions of tofacitinib treatment outcomes in patients with moderately to severely active UC., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CWL has served as a speaker for AbbVie, Dr Falk, Ferring, Hospira, Janssen, MSD, Pfizer Inc, Shire, Takeda, and Warner-Chilcott; has served as a consultant for AbbVie, Dr Falk, Gilead, GSK, Hospira, Iterative Scopes, Janssen, MSD, Oshi Health, Pfizer Inc, Pharmacosmos, Takeda, Topivert, Trellus Health, and Vifor Pharma; and has received research funding from AbbVie and Gilead. MC has served as a speaker for AbbVie, Janssen, Medtronic, Pfizer Inc, and Takeda; and has served as a consultant for AbbVie, Arena, BMS, Medtronic, Pfizer Inc, Prometheus, and Takeda. MD has received personal fees from AbbVie, Chiesi, Ferring, Janssen, MSD, Pfizer Inc, and Quintiles; has received grants and personal fees from Takeda; has received non-financial support from SOFAR; and has been involved in clinical trials for Eli Lilly, Galapagos, Gilead, Janssen, MSD, Roche, and Takeda. GB owns stocks and shares in Fair Dynamics Consulting, which is a paid consultant contracted by Health Services Consulting Corporation in connection with this study. JJD, RG, PBB, and IM are employees of, and owns stocks and shares in, Pfizer Inc. RAE is a Principal in Health Services Consulting Corporation, and was a paid consultant to Pfizer Inc in connection with this study., (© The Author(s), 2021.)