P322 Compared Efficacy of Second-Line Treatments for Ulcerative Colitis After Failure of Vedolizumab in First-Line Treatment: A Retrospective Multicenter Study
Authors: Calmejane L , Reenaers C , Amiot A , Nuzzo A , Vuitton L , Altwegg R , Guillo L , Wils P , Roblin X , Le Cosquer G , Simon M , Benezech A , Laharie D , Fumery M , Buisson A , Charkaoui M , Nancey S , Sabra G , Geyl S , Coffin B , Cavicchi M , Le Berre C , Goutorbe F , Bouguen G , Vidon M , Christmann P Y , Kirchgesner J , Uzzan M 
Published: January 2024

Background

Vedolizumab is often used as the first-line advanced therapy for patients with moderate to severe ulcerative colitis (UC). There is currently no data reporting the efficacy and safety of second-line treatments after initial vedolizumab failure. The objective of our study was to compare the efficacy of anti-TNF, ustekinumab, and tofacitinib as 2nd line treatment of UC after vedolizumab exposure.

Methods

We conducted a retrospective multicenter study in 27 French and Belgian centers. All consecutive UC patients treated with vedolizumab between January 2019 and June 2023 as the first line and who received a 2nd line of anti-TNF, ustekinumab or tofacitinib were retrospectively included. The primary outcome was clinical remission at induction (week 14) defined by a clinical partial Mayo score ≤ 2 with no subscore &gt; 1 without investigated treatment withdrawal. Clinical response was defined as a decrease in partial Mayo score of at least 30%.

Results

Among the 163 patients included, 94 (57.7%) were treated with anti-TNF (infliximab=71 (75.5%), adalimumab=21 (22.3%), and golimumab=2 (2.1%)), 56 (34.4%) with ustekinumab and 13 (7.9%) with tofacitinib. The median duration of the disease prior to second-line initiation was 9.5 months (IQR 16.0-146.0). The median duration of treatment with vedolizumab was 6 months (IQR 3.0-12.0). At week 14, 25/66 (37.9%) patients on infliximab, 7/23 (30.5%) on SQ anti-TNF (adalimumab and golimumab), 25/57 (43.9%) on ustekinumab and 7/13 (53.8%) treated with tofacitinib were in remission (p=0.49, Chi2 test). Response rates were 52.8%, 34.8%, 50.9%, and 53.8%, respectively, for the infliximab, antiTNF SC, ustekinumab, and tofacitinib groups.

The survival without treatment discontinuation att 12 months was estimated at 51.6 (95% CI [39.6%-67.2%]) for infliximab, 45.7% (95% CI [28.5%-73.1%]) for SQ anti-TNF, 40.6% (95% CI [27.2%-60.6%]) for ustekinumab and 31.2% (95% CI [12.3%-79.2%]) for tofacitinib (p=0.95, log-rank test). Second-line treatment was discontinued in 41 patients (25.3%) for primary failure, 25 (15.4%) for secondary failure. Colectomy was required in 4 patients (2.5%) during follow-up.

Infliximab was discontinued in 12 patients (12.8%) due to adverse reactions, including 6 allergic reactions. Among the 23 patients on SQ anti-TNF (adalimumab and golimumab), 2 required discontinuation (8.7%) due to adverse reactions. One side effect leading to discontinuation occurred with tofacitinib (7.7%) and none with ustekinumab.

Conclusion

After the failure of vedolizumab as a first-line biologic treatment for UC, the induction efficacy, persistence, and safety of the different second-line treatments seem similar. Current efforts to increase the sample size and strengthen the analysis is ongoing.