P028  Outcomes of standard and intensified dosing of ustekinumab for chronic pouch disorders

P028  Outcomes of standard and intensified dosing of ustekinumab for chronic pouch disorders

Dalal Rahul1, Gupta Sanchit1, Allegretti Jessica1
1 Brigham and Women's Hospital, Boston, United States

BACKGROUND: Patients with chronic antibiotic-refractory pouchitis and Crohn's disease (CD) of the pouch are often treated with biologic agents. Data regarding the efficacy of ustekinumab therapy dosed every 8 weeks (q8w) and intensified dosing to q6w or q4w for these conditions is limited. We sought to assess outcomes of standard and intensified ustekinumab dosing and identify factors associated with clinical response among patients with chronic pouch disorders.

METHODS: This retrospective cohort study included adults initiated on ustekinumab for chronic pouch disorders between 1/1/2016 and 3/1/2020. Electronic health records were reviewed to obtain demographic and clinical data. The primary outcome was physician-reported clinical response 2-4 months after ustekinumab initiation (q8w) or dose intensification (q6w or q4w). The secondary outcome was time to dose intensification. Additional outcomes included pouch excision with permanent ileostomy, improvement in the 6-point clinical subscore of the pouchitis disease activity index (PDAI), IBD-related hospitalization, improvement in severity/extent of inflammation on pouchoscopy, and discontinuation of chronic antibiotics. Univariable logistic and cox regression were used to identify characteristics associated with primary and secondary outcomes, respectively.

RESULTS: 46 patients were initiated on ustekinumab for pouchitis (n=6), cuffitis (n=4), or CD of the pouch (n=36). Outcomes after initiation were as follows (denominators vary due to missing data or insufficient follow-up time): 80.4% (37/46) of patients had a physician-reported clinical response at 2-4 months, 50.0% (23/46) underwent dose intensification after a median of 223 days, 8.7% (4/46) had a permanent ileostomy after a median of 571.5 days, 59.1% (26/44) had an improvement in PDAI clinical subscore at 2-4 months, 16.2% (6/37) were hospitalized within 12 months, 53.6% (15/28) of those who underwent pouchoscopy after initiation had improvement in pouch inflammation, and 30.8% (4/13) of patients on chronic antibiotics discontinued antibiotics within 12 months. Logistic regression demonstrated that female sex (OR 10.5; 95% CI 1.2-92.7; p=0.03) and pouch fistula (OR could not be calculated; 37.8% clinical response vs. 0.0% no clinical response; p=0.04 by Fisher's exact test) were positively associated with clinical response after initiation and cannabis use (OR 0.15; 95% CI 0.03-0.75; p=0.02) was inversely associated with clinical response. Cox regression demonstrated that younger age at IBD diagnosis (HR 0.94; 95% CI 0.90-0.99; p=0.01) and younger age at initiation (HR 0.96; 95% CI 0.92-0.99; p=0.04) were associated with shorter time to dose intensification. After dose intensification to q4w or q6w, there were similar rates of clinical response at 2-4 months (61.9% q4w, 66.7% q6w), improvement in pouchoscopy (70.0% q4w, 75.0% q6w), and improvement in PDAI clinical subscore (47.6% q4w, 46.7% q6w) at 2-4 months. One patient experienced an adverse event (acneiform reaction), leading to ustekinumab discontinuation 807 days after dose intensification. On logistic regression analysis, no baseline characteristics were significantly associated with clinical response after dose intensification.

CONCLUSION(S): While ustekinumab was effective for the majority of patients in our cohort, nearly 50% ultimately required dose intensification, which was effective in recapturing response for most patients. Larger, prospective studies are needed to determine the optimal subpopulations in which to employ various dosing strategies of ustekinumab for chronic pouch disorders.