DOP092 Efficacy and safety of a second JAK inhibitor in Ulcerative Colitis : J2J multicenter cohort
Authors: Osty M , Altwegg R , Serrero M , Benezech A , Cadiot G , Vuitton L , Wampach A , Nancey S , Buisson A , Le Berre C , Rouillon C , Gilletta C , Goutorbe F , Fumery M , Hammoudi N , Caillo L , Vidon M , Arab N , Sickersen G , Cavicchi M , Vieujean S , Wils P , Caron B , Amiot A , Nuzzo A , Laharie D , Kirchgesner J , Uzzan M 
Published: January 2025

Background

Very few data exist on the use of a second JAK inhibitor (JAKi) in patients with ulcerative colitis (UC), already exposed to a first line of JAKi. The aim of this study was to evaluate the efficacy and safety of a second line of JAKi in UC.

Methods

We conducted an ambispective observational multicenter study in 28 Belgian and French centers. All patients with refractory UC, previously exposed to a first-line JAKi and subsequently receiving another JAKi, were included between July 2019 and September 2024. The primary endpoint was corticosteroid-free clinical remission at the end of the induction period (weeks 8-14), defined by a partial Mayo score ≤ 2 without any subscore &gt; 1.

Results

A total of 153 patients, 61% men, with a median age at diagnosis of 23 years (IQR [18.1-34.7]), were included and followed up for a median of 3 months (IQR [2- 10.9]). The median duration of disease was 7 years (IQR [4.2- 11.9]) and 90% of patients had been exposed to at least two biologics (excluding JAKi). The first-line JAKi was tofacitinib for 107 patients (70%), filgotinib for 38 (25%) and upadacitinib for 8 patients (5%). At baseline, the median partial mayo score was 6 (IQR [5-8]), the median CRP was 4.6 mg/L (IQR [1.5-14]) and the median fecal calprotectin was 611 μg/g (IQR [325-1488]). In second-line treatment, 96 patients (63%) received upadacitinib, 48 (31%) filgotinib and 9 (6%) tofacitinib. Follow-up data for the induction period were available for 125 patients. At week 8-14, 57/125 patients (46%) were in corticosteroid-free remission, including 40/78 on upadacitinib (51%), 15/40 (38%) on filgotinib and 2/7 (29%) on tofacitinib. No significant difference was found in steroid-free remission rates between upadacitinib and filgotinib at induction (p=0.19). Clinical response was achieved in 57 patients (73%) on upadacitinib, 23 patients (58%) on filgotinib and 5 patients (71%) on tofacitinib. The median partial Mayo score, CRP and calprotectin were 2 (IQR [0 ;3]), 1 (IQR [1 ;6.7]) and 385 μg/g (IQR [90 ;855]) respectively, for the overall population. Among the 23 patients (18%) who discontinued treatment before weeks 8-14, the reason was primary failure for 16 patients (70%) and an adverse event for 6 (26%). During the induction period, 14 patients (18%) on upadacitinib experienced AEs, the most frequent being acne; 8 (19%) on filgotinib; and 2 (29%) on tofacitinib. No cases of herpes zoster, cancer or vascular accident were observed. Seven (5%) patients underwent colectomy during follow-up.

Conclusion

In refractory UC, 46% of patients treated with a second JAKi were in corticosteroid-free remission at the end of the induction phase, with no significant difference based on the molecule used.