Background: Ustekinumab (UST), an interleukin-12/23p40 inhibitor, is effective in Crohn's disease (CD). Little is known on its efficacy in perianal fistulizing disease. To date, perianal outcomes using UST have been reported in only 18 patients. We report on the efficacy of UST on perianal fistulizing disease in CD. We also describe UST trough concentration, clinical, biomarker and endoscopic response in CD patients with perianal fistulas.
Methods: Anti-TNF refractory CD patients treated with UST (2013–2015) at the McGill University Health Centre were recruited. All patients were induced with UST 90mg SC at week 0, 1, 2 then maintained with UST 90mg SC every 4 or 8 weeks. At 6 months 77.4% were receiving UST every 4 weeks. The primary endpoint was >50% reduction from baseline in the number of draining fistulas. The secondary endpoint was closure of all fistulas. Outcomes were assessed for longitudinal patients and cross sectional patients ≥6 months. A combined cohort was analyzed at ≥6 months, when available. UST and UST antibody concentrations were assessed using a liquid phase assay (HMSA, Prometheus Laboratories, San Diego, CA, USA).
Results: Sixty-two patients were recruited. 17 patients had a history of perianal fistulizing disease. 6 patients had actively draining fistulas prior to initiating UST. At ≥6 months, 66% (4/6) of patients had a >50% reduction from baseline in the number of draining fistulas, and 33% (2/6) patients had closure of all fistulas. At ≥6 months, of the 6 patients who had active fistulas at commencement of UST, 3/6 (50%) attained clinical response while 2/6 (33%) attained clinical remission as determined by HBI assessment (HBI<5). 2/6 (33%) achieved steroid free clinical remission. Endoscopic response was attained in 3/6 (50%) patients while 2/6 (33%) attained endoscopic remission. Mean UST trough concentration at ≥ week 26 was 4.85 ug/ml. In those with >50% reduction in draining fistulas (n=4) mean UST trough concentrations were 5.0 ug/ml compared to 4.6 ug/ml in those without (n=2).
Conclusions: UST was effective in achieving reduction in perianal fistulas in a small series of anti-TNF refractory CD patients. Given the limited information on this subject, this series adds to the existing data on response of perianal fistulas with UST. However, larger studies are required to confirm these findings.