Effectiveness and Safety of a Second <scp>JAK</scp> Inhibitor in Ulcerative Colitis: The <scp>J2J</scp> Multicentre Study
Mathilde Osty, Romain Altwegg, Mélanie Serrero, Alban Benezech, Albane Lecomte, Guillaume Cadiot, Lucine Vuitton, Anne Wampach, Stéphane Nancey, Anthony Buisson, Catherine Le Berre, Cléa Rouillon, Cyrielle Gilletta, Félix Goutorbe, Mathurin Fuméry, Nassim Hammoudi, Ludovic Caillo, Mathias Vidon, Nadia Arab, Gaëlle Sickersen, Maryan Cavicchi, Sophie Vieujean, Maëva Charkaoui, Nicolas Richard, Pauline Wils, Bénédicte Caron, Aurélien Amiot, Alexandre Nuzzo, David Laharie, Julien Kirchgesner, Mathieu Uzzan, GETAID‐J2J group
Abstract
BACKGROUND: While three Janus kinase inhibitors (JAKi) have demonstrated efficacy in ulcerative colitis (UC), scarce data exist regarding JAKi intraclass switching. AIM: To evaluate the effectiveness and safety of a second JAK inhibitor in UC. METHODS: This was a multicentre, retrospective, observational cohort including patients with moderate to severe UC who received a second-line of JAKi after failure or intolerance of a first. The primary outcome was steroid-free clinical remission (SFCR) at Weeks 8-14, defined as a partial Mayo score of 2 or less with no individual sub-score above 1. RESULTS: Among the 169 patients from 28 participating centres, 105 received upadacitinib, 54 filgotinib and 10 tofacitinib as a second-line of JAKi. Overall, 81/169 achieved SFCR at Weeks 8-14: 58/105 with upadacitinib, 18/54 with filgotinib and 5/10 with tofacitinib (p = 0.03). In the multivariate analysis, upadacitinib was independently associated with higher odds of SFCR than filgotinib (OR = 3.15, 95% CI [1.52-6.79]). With a median follow-up duration of 96 days, drug persistence at 6 months was 72.8% with upadacitinib, 57.2% with filgotinib and 66.7% with tofacitinib (p = 0.099). 24.3% of patients (41/169) experienced at least one adverse event leading to treatment withdrawal in 9 patients (5%). No cases of death, cancer, or major acute cardiovascular events were reported. CONCLUSION: A second-line of JAKi provided clinical remission in about half of patients after induction, and was well tolerated.