89 Efficacy and Safety of Ustekinumab in Patients With Primary Sclerosing Cholangitis–Associated Inflammatory Bowel Disease

Background: Primary sclerosing cholangitis (PSC) with inflammatory bowel disease (IBD) represents a unique disease phenotype associated with an increased risk of colorectal cancer and progressive liver disease. Despite the availability of biologics, data on the efficacy and safety of ustekinumab in PSC-IBD are extremely limited. We aimed to assess clinical outcomes and safety profile of ustekinumab in this population at a single tertiary referral center. Methods: We conducted a retrospective observational study of PSC-IBD patients treated with ustekinumab at Mayo Clinic between January 1, 2018 and January 1, 2024. Demographics, prior exposure to advanced IBD therapies, ursodeoxycholic acid use, and presence of portal hypertension at baseline was collected. Disease activity at baseline was assessed using the Mayo Score (stool frequency, rectal bleeding, mucosal appearance at endoscopy, and physician global assessment; 0–12 scale), with mucosal appearance at colonoscopy defined by the Mayo endoscopic subscore. Outcomes included treatment discontinuation, reasons for discontinuation, and safety events. Comparative analyses were performed between patients who discontinued ustekinumab and those who remained on therapy. Results: A total of 20 PSC-IBD patients (55% male) treated with ustekinumab were included. The cohort had a median age of 32.5 years (IQR 28.5–42.3) at the time of ustekinumab initiation. Initial ustekinumab dosing was 390 mg in 45% of patients, 520 mg in 35%, and 260 mg in 20%. At baseline, 25% of patients were receiving ursodeoxycholic acid. Prior to ustekinumab, 70% had been treated with infliximab, 70% with vedolizumab, 70% with adalimumab, and 15% with tofacitinib; overall, 50% had received 3 or more advanced therapies before ustekinumab. One patient (5%) had evidence of clinically significant portal hypertension with esophageal varices. At baseline colonoscopy, the median Mayo endoscopic subscore was 2 [2–3], and the overall median Mayo Score was 6.5 [5–8]. During follow-up, 13 patients discontinued ustekinumab after a median of 0.83 years [0.58–1.08], including 3 due to insurance coverage and the remainder for lack of efficacy, while 7 patients remained on therapy at the time of data collection. Patients who discontinued therapy due to lack of efficacy were younger at initiation compared with those who continued (median 32 years [26–34] vs 42 years [30–49.5]; P = 0.23) and had higher baseline mucosal appearance subscores (median 3 [2–3] vs 2 [1–3]; P = 0.17). Baseline Mayo Scores were significantly higher in the discontinued group (median 8 [6–9] vs 5 [4–6]; P = 0.018). No patients experienced adverse events while on ustekinumab, with no cases of thrombosis, infections, lymphoproliferative disease, new signs of cirrhosis, or neoplasia observed. Conclusions: In this single-center PSC-IBD cohort, ustekinumab was safe and generally well tolerated, with no adverse events observed. More than half discontinued therapy for lack of efficacy, while those who remained tended to have less severe baseline disease. Larger studies are needed to confirm efficacy and identify predictors of sustained response.