Patients With Refractory Crohn’s Disease Successfully Treated With Ustekinumab

Abstract

Introduction: Ustekinumab is a new a biologic therapy targeting interleukin (IL)-12 and IL-23. It is currently approved for the treatment of psoriasis, but clinical trials have shown that it can induce and maintain remission in Crohn’s disease (CD). We aim to evaluate ustekinumab effectiveness in treatment of CD. Methods: A retrospective multicenter chart review was performed including patients with complicated, refractory CD started on ustekinumab between June 2011 and June 2014. Patients were treated based on a novel subcutaneous (SQ) dosing schedule designed to simulate the IV load utilized in clinical trials. Induction dosing of 90 mg at weeks 0, 4, and 12 was used, with a 270 mg booster dose at week 8 if no or limited response. The maintenance dose used was 90 mg every 8 weeks. Outcomes measured included HBI and SIBDQ scores, CRP and sedimentation rate, and endoscopic response (all measured at a minimum of 90 days from initiation of treatment) as well as hospitalization or surgery. Statistical analysis was performed using Wilcoxon matched-pairs sign-rank test. Results: Forty-five patients were treated with ustekinumab during this study period. Median follow-up was 289 days (range 61, 1,067 days). Seventy-one percent were female with median age of 34 years (range of 20 to 73 years). Eighty-two percent were white and 20% were current smokers. The median duration of disease was 13 years (range 4-38 years). Disease location included: 9% upper gut disease, 77% ileal disease, 91% colonic disease, and 24% perianal disease. Seventy-three percent had prior surgery related to CD and 7% had an ostomy. One hundred percent of patients had at least one prior anti-TNF therapy. Seventy-one percent were on budesonide or prednisone, and 65% were on concurrent immunomodulator therapy. Thirty patients had clinical parameters available before and after medication start. Fifty-seven percent of patients achieved either clinical response (HBI decrease >3) or remission (HBI <3), and 33% achieved clinical remission. SIBDQ scores increased significantly (46 [20, 68] to 55 [32, 70]; p<0.05). ESR decreased (20 [3, 54] to 17 [0, 42]; p=0.05). CRP decreased significantly (6.8 [0.3, 11] to 4.2 [0.2, 226]; p <0.05). Sixty-eight percent of patients demonstrated an endoscopic response and 9% achieved complete endoscopic remission. Twelve patients (26%) were hospitalized for IBD related issues (6 for surgery and 6 for IBD-related symptoms). Four patients had infectious related complications, 3 with perianal/pelvic abscesses, 1 with UTI. Six patients (13%) underwent surgery for IBD related issues. Three patients stopped ustekinumab, 1 for patient preference, and 2 for lack of response. Conclusion: Ustekinumab utilizing a novel SQ dosing schedule was successful in a group of patients with severe, refractory CD with significant improvements in clinical, inflammatory marker, and endoscopic response.