Ustekinumab for Crohn's disease: results of the ICC Registry, a nationwide prospective observational cohort study.

Biemans, Vince B C; van der Meulen-de Jong, Andrea E; van der Woude, Christine J; Löwenberg, Mark; Dijkstra, Gerard; Oldenburg, Bas; de Boer, Nanne K H; van der Marel, Sander; Bodelier, Alexander G L; Jansen, Jeroen M; Haans, Jeoffrey J L; Theeuwen, Rosaline; de Jong, Dirk; Pierik, Marie J; Hoentjen, Frank

BACKGROUND AND AIMS Ustekinumab is approved for the treatment of Crohn's disease (CD). Systematically registered prospective real-world data is scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practise. METHODS We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index (HBI)), biochemical (C-reactive protein (CRP) and faecal calprotectin (FCP)), extra-intestinal manifestations, and peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at week 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission. RESULTS In total, 221 CD patients were included (98.6% anti-TNF and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks (IQR 49.3-58.4). The corticosteroid-free clinical remission rates at week 24 and 52 was 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate (20.0% vs. 42.6%, p=0.01), but comparable corticosteroid-free clinical remission at week 52 (46.3% (q8w) vs. 34.6% (q12w), p=0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy (combi 40.6% vs. mono 36.0% p=0.64). At baseline, 28 patients had active peri-anal fistula, of which 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections (3.5 per 100 patient years), all patients were on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 (33.9%) patients mainly due to lack of response. CONCLUSION Ustekinumab is relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.