Introduction
Upadacitinib (UPA) has shown promising results in the pivotal trials, which require validation in clinical practice. Primary aim: To assess the durability of UPA treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short and long-term effectiveness, dose optimization and response to dosage adjustments, the impact of extraintestinal manifestations (EIM) and immunomediated diseases (IMIDs), and the tolerability of UPA in UC in a real-world setting.
Aims & Methods
Adult patients who started UPA for UC treatment at least 8 weeks prior to data collection and were part of the prospectively maintained ENEIDA registry of GETECCU were included. Patients on concomitant biologic agents or with a history of colectomy were excluded. Patients were followed-up from the first UPA dose until treatment discontinuation or the last visit. Effectiveness analysis was restricted to patients with active disease [Partial Mayo Score (PMS)>2] at UPA initiation. Clinical effectiveness was measured using PMS, and concomitant steroid use was assessed at each visit. Patients who discontinued UPA before their last visit were considered not in remission at subsequent time points (negative imputation).
Results
The study included 168 patients, 89% with active disease; 48% had been previously exposed to JAK inhibitors (JAKi), and 31% to all approved therapeutic targets. Mean time of follow-up was 5.6 months (interquartile range = 2.7-11 months). The proportion of patients under 45 mg/day of UPA was 77% at week 8 and 40% at week 16. A total of 29 patients discontinued treatment during a median follow-up time of 4.3 months. The incidence rate of UPA discontinuation was 27% per patient-year of follow-up, with no significant differences related to prior JAKi exposure (log-rank p-value > 0.05). The main reason for UPA discontinuation was loss of response (34%), with colectomy being the main subsequent treatment (21%). No predictive factors for UPA discontinuation were identified (including severity, number of previous advanced therapies, and prior JAKi exposure). Proportions of patients in steroid-free clinical remission (SFCR) were 67%, 71%, 65%, 60% and 75% at week 8, week 16, month 6, month 12 and month 18, respectively. In multivariate analysis, PMS at baseline [Odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63-0.98] and previous exposure to JAKi (OR = 0.29, 95%CI = 0.14-0.61) were associated with lower probability of SFCR at week 8. Among 100 patients in SFCR at week 8, 13 (13%) lost response (31% per patient-year), and 10 (77%) of these had dose escalation, with 9 (90%) regaining SFCR. Of 31 patients (18%) with active EIM/IMIDs at the start of UPA, 15 (48%) showed improvement. Adverse events occurred in 45 patients (27%), with hypercholesterolemia being the most common, but no major cardiovascular or thromboembolic events were reported.
Conclusion
This study, the largest of its kind in clinical practice, confirms the short- and long-term benefits and the safety profile of UPA for UC. Although prior JAKi exposure reduced short-term effectiveness, it did not impact drug survival, indicating that UPA could be a viable option even for patients who have experienced JAKi failure.
Disclosure
María Chaparro has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.
Luisa de Castro has received grants for conference attendance from Abbvie, Johnsson and Johnsson, Takeda, Falk and Pfizer. She has received grants or participated as a speaker for Johnsson and Johnsson, Falk and Tillots.
Iago Rodríguez Lago has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Biogen, Celltrion, Chiesi, Faes Farma, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, Mirum Pharmaceuticals, MSD, Pfizer, Roche, Takeda, and Tillotts Pharma. Research support from AbbVie. Iago Rodriguez Lago is supported by a research grant from Gobierno Vasco-Eusko Jaurlaritza [Grant No 2020111061].
Carla J. Gargallo-Puyuelo Conflicts with Abbvie, Takeda, Janssen, Ferring, Lilly.
Marisa Iborra reports grants and personal fees from MSD, Janssen, Abbvie, Takeda, Kern and Pfizer, during the conduct of the study.
Manuel Barreiro has served as a speaker, consultant and advisory member for or have received research funding from MSD, AbbVie, Janssen, Kern Pharma, Celltrion, Takeda, Gillead, Celgene, Pfizer, Sandoz, Biogen, Fresenius, Ferring, Faes Farma, Dr. Falk Pharma, Chiesi, Gebro Pharma, Adacyte, Vifor Pharma and Oncostellae.
Ruth de Francisco has received support for conference attendance, and research support from AbbVie, Faes Pharma, Ferring, Janssen, Pfizer, Takeda, and Galapagos.
R Pajares Villarroya has received financial support for educational activities from Takeda.
Trapero Martínez Ana María Conflict of interest; Abbvie, Jansen, Lilly, MSD.
Lara Arias García scientific advice, research support and/or training activities for Abbvie FAES Pharma, Kern Pharma, Ferring and MSD.
Raquel Camargo has received funding for different types of training activities from Johnson&Johnson, Avbbie, Pfizer, Ferring, Falk and Galapagos.
Margalida Calafat has served as a speaker or has received research or education funding or advisory fees from Takeda, Janssen, Faes Farma, Falk, Abbvie, Pfizer, Adacyte Therapeutics, Ferring, Gilead, Kern Pharma, and MSD.
MT Diz-Lois Palomares has received funding for training activities/congresses/lectures: Abbvie, Ferring, Johnson and Johnson, Lilly, Takeda.
F. Bermejo has been a speaker, consultant and advisory member or has received research funding from Abbvie, Takeda, Janssen, Pfizer, Lilly, MSD, Biogen, Amgen, Galapagos, Ferring, Faes Farma, Tillotts Pharma, Chiesi, Vifor Pharma.
Marta Calvo Moya has received support for conference attendance, speaker fees, research support, and consultancy fees from AbbVie, MSD, Takeda, Janssen, Pfizer, Lilly, Shire, Chiesi, DrFalk Pharma, Faes Pharma, Ferring, Kern Pharma, and Tillotts Pharma.
MJ Casanova, has received education funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos and Abbvie.
Francisco Mesonero has received funding for educational activities, conferences and scientific advice/consultations from MSD, AbbVie, Takeda, Janssen, Pfizer, Ferring, Kern Pharma, Dr. Falk Pharma, Celltrion Healthcare, Galapagos, Chiesi, Tillots Pharma and Faes Farma.
Yamile Zabana has received support for conference attendance, speaker fees, research support and consulting fees from: AbbVie, Adacyte, Alfa-Sigma, Almirall, Amgen, Boehringer Ingelheim, Dr Falk Pharma, FAES Pharma, Fresenius Kabi, Ferring, Galapagos, Janssen, J&J, Kern, Lilly, MSD, Otsuka, Pfizer, Sanofi, Shire, Takeda, Tillots.
Mónica Sierra has participated as a speaker and attended courses financed by MSD, Abbvie, Takeda, Pfizer, Lilly, Ferring, Sandoz.
B Caballol has received support for congress and conference attendance, speaker fees, research support or consulting fees from Abbvie, Ferring, Janssen, Pfizer, Takeda, Galapagos, Kern Pharma and Lilly.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.
