P340. Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn's disease - the McGill experience
U. Kopylov1, W. Afif2, A. Cohen3, A. Bitton1, G. Wild1, T. Bessissow1, J. Wyse3, T. Al-Taweel1, A. Szilagy3, E.G. Seidman1, 1McGill University Health Center, Gastroenterology, Montreal, Canada, 2McGill University, Division of Gastroenterology, Montreal Quebec, Canada, 3Jewish General Hospital, Department of Gastroenterology, Montreal, Canada
Ustekinumab is a fully human IgG1monoclonal antibody that blocks the p40 subunit of interleukin-12/23. Ustekinumab is approved for treatment of plaque psoriasis. It was reported to be effective for induction amd maintenance treatment of anti-TNF resistant CD.
Aim: To describe a real-life experience with open-label use of subcutaneous ustekinumab in anti-TNF resistant CD patients, in a tertiary referral center setting.
A retrospective observational study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. Clinical endpoints were over 12 months of follow-up or discontinuation of ustekinumab. The primary outcome was clinical response by 3 months. Secondary outcomes included clinical response at 6 and 12 months and steroid-free response at each time-point.
Patient characteristics: 37 patients were treated with subcutaneous ustekinumab between 2/2011 to 7/2013 (median follow up: 5 (3–12) months). The demographic and clinical characteristics of the patients were as follows: male 50%, age 37 (21–62) years, age at diagnosis 20.5 (2–54) years. The disease characteristics were as follows: location - ileal 16.2%, colonic 18.9%, ileocolonic 64.9%; disease phenotype - luminal 46%, penetrating 43.2%, stricturing 10.8%; 40.5% had perianal involvement; 27.5% had previously undergone total proctocolectomy. Previous treatment included at least one biologic in all patients, two biologics in 86.7% and three biologics in 18.9%. A loading dose was administered in 89% of the patients: 90 mg at weeks 0, 1, 2 - 80%; 45 mg at weeks 0 and 4 - 12%, 90 mg at weeks 0 and 4 - 8% of the patients. Initial maintenance dosing included: 90 mg q8 wk - 73%, 90 mg q4 wk - 21.6%, 45/90 mg q12wk - 12 5.2% of the patients. The mean duration of follow-up was 6.1±3.9 months. Follow-up data was available for 37, 24 and 16 patients at 3, 6, and 12 months, respectively.
Treatment outcomes: Clinical response at 3 months was achieved in 22/37 (59.5%) of the patients; 11 (50%) of these patients were steroid-dependent at treatment onset, 7/11 (63.6%) were able to discontinue corticosteroids and 18.2% to decrease the dose by at least 50%. At 6 months, among the 15 patients with follow-up data available, 11 (73%) were still responsive; 3 additional patients were non-responders at 3 months but responded at 6 months. At 12 months, follow-up data was available for 9/25 of earlier responders;6/9 (66%) maintained their response; all were steroid-free.
In this cohort of severe anti-TNF resistant CD patients, initial response to subcutaneous ustekinumab resulted in clinical response in almost 60% of patients, with the majority of responders sustaining the benefit for 6–12 months.