The Effectiveness of second-and-third line biologics in perianal Crohn's disease - a multicenter propensity score-matched study.

Objective: Anti-tumor necrosis factor-α inhibitors (anti-TNFs) are the established treatment for perianal Crohn's disease (pCD), but relapse and non-response are common. Data on 2nd- and 3rd-line biologics are limited. We present the first direct comparison of 2nd - and 3rd -line biologics in pCD patients with active perianal disease previously treated with 1st-line anti-TNFs.

Methods: A multicenter retrospective cohort study included adult patients with pCD who failed 1st-line anti-TNF. The primary outcome was clinical perianal response, with secondary outcomes of radiological response (magnetic resonance imaging [MRI] or transrectal ultrasound [TRUS]) and healing, and clinical remission. Propensity-score matching (PSM) was used to adjust for baseline differences.

Results: A total of 486 pCD patients from 23 IBD centers were included, with 333/486 (68.5%) and 216/263 (82.1%) matched by PSM in the 2nd and 3rd -line treatment groups, respectively. In the 2nd -line group, 62/78 (79.5%) of ustekinumab (UST)-treated patients achieved clinical perianal response, compared to 46/78 (58.9%) with vedolizumab (VDZ) (OR 4.47, 95% CI 1.94-10.28, p<0.001) and 38/78 (48.7%) with anti-TNFs (OR 5.29, 95% CI 2.39-11.71, p<0.001). In the 3rd-line group, 38/49 (77.6%) of UST-treated patients achieved clinical perianal response, compared to 29/49 (59.2%) with VDZ (OR 9.96, 95% CI 2.6-38.4, p<0.001) and 27/49 (55.1%) with anti-TNFs (OR 12.03, 95% CI 2.99-48.47, p<0.001). UST-treated patients also had higher radiological response rates than VDZ (OR 3.28, 95% CI 1.07-10.07, p=0.038).

Conclusions: In pCD patients failing anti-TNFs as 1st-line treatment, ustekinumab may be more effective than vedolizumab or another anti-TNFs as 2nd or 3rd-line therapy.