Effectiveness and safety of third-line advanced therapies in patients with ulcerative colitis: A multicentre retrospective cohort study: Third-line treatment in UC.

Background: The effectiveness of advanced therapies beyond second-line therapies has been poorly described in patients with ulcerative colitis (UC).

Aim: To describe the outcomes of third-line advanced therapy in patients with UC in a real-world setting.

Methods: We conducted a multicentre retrospective study in patients with UC who received third-line advanced therapy after the failure of a first-line anti-TNF agent and second-line vedolizumab. The primary endpoints were steroid-free clinical remission at weeks 14 and 54.

Results: We analysed 237 therapeutic sequences in 150 patients (55 with an anti-TNF agent, 80 with tofacitinib, and 102 with ustekinumab), accounting for 245.3 patient-years. Steroid-free clinical remission at week 14 was achieved in 14 (25.5 %) patients treated with an anti-TNF agent, 40 (50.0 %) with tofacitinib, and 54 (52.9 %) with ustekinumab (RR = 1.96 [1.19-3.25] for tofacitinib and RR = 2.08 [1.28-3.39] for ustekinumab, compared with an anti-TNF agent, respectively). Steroid-free clinical remission at week 54 was achieved in 16 (29.1 %) patients in the anti-TNF group, 37 (46.2 %) in the tofacitinib group and 56 (55.4 %) in the ustekinumab group (RR = 3.07 [0.98-9.60] for tofacitinib and RR = 3.09 [1.01-9.43] for ustekinumab, compared with anti-TNF, respectively). In total, 13.7 % of the patients underwent colectomy. Adverse events occurred in 94 (39.7 %) patients and were less frequent with ustekinumab.

Conclusion: In this retrospective study, third-line advanced therapies resulted in a high rate of steroid-free clinical remission at weeks 14 and 54, especially in patients treated with ustekinumab and tofacitinib.