Efficacy of Ustekinumab Therapy in Patients With Perianal Crohn's Disease

Introduction: There remains a paucity of data in a real-world setting for the efficacy of ustekinumab (UST) use in patients with perianal Crohn’s disease (pCD). In this study, we sought to describe the outcomes of patients with pCD treated with UST. Methods: A retrospective review of electronic health records from a tertiary care center between 1/1/2017 and 1/31/2022 was conducted. Adult patients with a documented history of pCD and treatment with UST were included. Perianal (PA) disease was defined as clinical documentation of a PA fistula or abscess. Patient demographics, inflammatory bowel disease history, and biologic history were collected. Laboratory data, clinical assessments, and interventions were documented through 12 months of UST therapy. PA disease response was defined as >50% reduction in drainage and number of fistulae from baseline. Results: 131 patients with pCD treated with UST were identified. Of those, 43 patients had active PA lesions at the time of UST initiation. In this subgroup, the average age was 39.9 years (SD: 11.3 years) and CD median duration was 15 years (range: 0.42-45 years). 53% of patients were male. 88% of patients were previously treated with infliximab and 72% treated with adalimumab. 76% of patients underwent a prior PA procedure with 47% having at least 2 prior PA procedures. At 3 months and 12 months after UST initiation, 33% and 52% of patients had a response to therapy, respectively (Table 1). 85% of those with a response at 6 months vs. 44% without response were continued on UST at 5.5 years (P=0.028). By 12 months of UST therapy, 44.8% required antibiotics for PA disease. At baseline, the median C-reactive protein (CRP) was 0.97mg/dL (IQR 0.13-4.4). After 12 months of UST therapy, the median CRP was 0.7mg/dL (IQR 0.29-1.5). This decrease trended toward significance (P=0.059). Please see Table 1 for other objective lab data. In the inactive pCD group of 88 patients, 9 patients (10.2%) had PA disease recurrence with 6 undergoing a perianal procedure by 12 months of UST initiation. Conclusion: In this cohort, most patients were exposed to anti-TNFs and had a history of a perianal procedure. Of those with inactive perianal disease, a majority remained inactive and intervention-free through 12 months of UST therapy. In those with active disease, >50% experienced a fistula response and remained antibiotic-free by 12 months of therapy. This study suggests that UST is an effective option for treatment of active pCD and for prevention of PA disease recurrence. Table 1. - Clinical and Laboratory Indices at Specific Timepoints after Ustekinumab Initiation in Patients with Perianal Crohn's Disease 3 Months 6 Months 12 Months Perianal Assessment No Change from Baseline (%) 66.7 58.1 48.4 Fistula Response (%) 33.3 41.9 51.6 Median CRP mg/dL (IQR) 1.5 (0.6-4.0) 1.1 (0.5-3.0) 0.7 (0.3-1.5) Calprotectin mcg/g (IQR) 318 (144-1660) 199 (191-239) 261 (129-596)