An Steig- Stelara Treatment Effectiveness in Irish Gastroenterology; a multicentre retrospective analysis of treatment outcomes with Ustekinumab in Crohn’s Disease.
Catherine Rowan*1,2, Alaa Alakkari*3, Carthage Moran 4, Jim O’Connell 5,Garret Cullen 1,2, Colm O’Morain 3, Aoibhlinn O’Toole 4, Stephen Patchett 4 ,Susan McKiernan 5 ,David Kevans 5 , Glen A. Doherty*1,2 & Barbara Ryan*3
1. Centre for Colorectal Disease, St. Vincents University Hospital, Dublin, Ireland 2. School of Medicine, University College Dublin, Ireland 3. Department of Gastroenterology, Tallaght Hospital, Tallaght, Dublin 24, Ireland 4. Department of Gastroenterology, Beaumont Hospital, Dublin 9, Ireland 5. Department of Gastroenterology, St.James’s Hospital, Dublin 8, Ireland
A previous trial of Ustekinumab in Crohn’s disease patients demonstrated a clinical response rate of 39.7% 1 with Phase 3 studies awaiting publication.
To evaluate the Irish experience of Ustekinumab in Crohn’s Disease (CD) 2011-2016
A multicentre retrospective analysis of patients with CD treated with Ustekinumab was performed through the INITiative IBD Network. Data collected included patient demographics, disease distribution, previous treatments, surgery, concomitant therapies, induction dose, escalation of therapy, surgery post-treatment, sustained benefit at 12 months.
44 patients (15 male; 7 smokers) were included. Median age was 39.5 years (IQR 30.75-49.75years).Median duration of follow-up was 589 days (IQR 371-1114 days). 41 patients (93%) had prior Crohn’s-related surgery, with 27 patients (34%) having more than 1 surgical procedure. All patients had been treated previously with at least 1 anti-TNF agent. 22.7% of patients had failed therapy with 3 anti-TNF agents. Various induction regimens were utilised. All patients received subcutaneous induction dosing.The median cumulative induction dose was 225mg (range 135-270mg). 18.2% (n=8) were taking concomitant immunomodulators and 25% concomitant steroids at induction. In 16 cases (36.4%) the dose or frequency of Ustekinumab was escalated. 12 patients had a sustained clinical benefit at 12 months. 21 patients of 44 (48%) had sustained benefit at 12 months; 2 patients subsequently discontinued therapy. The median duration of treatment for the entire cohort was 365 days (IQR 90-969 days). 11 patients had surgery while on Ustekinumab. Failing 3 anti-TNF therapies was significantly associated with requiring surgery in the 12 months post-induction with Ustekinumab. (P=0.017) In regression analysis escalation of therapy was significantly associated with sustained benefit at 12 months (p=0.017), while concomitant immunomodulators, steroids and cumulative induction dose were not.
In this study, Ustekinumab provided sustained clinical benefit to almost half of patients with medically-refractory Crohn’s Disease. These data suggest that induction therapy with subcutaneous Ustekinumab may be an alternative to iv induction. The findings highlight that escalation of therapy is associated with sustained benefit at 12 months. As with anti-TNF therapy, dose optimisation appears to be critical in inducing and maintaining response with Ustekinumab.