S1935 Advanced Combination Therapy of Upadacitinib and Biologic Therapy in Refractory Inflammatory Bowel Disease Patients

Introduction: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), has increased globally in recent decades. Despite therapeutic advances, remission rates remain modest (30–40% at 12 months). This study aims to assess the safety and efficacy of advanced combination therapy (ACT) using upadacitinib and another biologic in patients with IBD. Methods: This is a retrospective, single centre study that included patients ≥14 years with confirmed IBD [CD, UC, IBD-unclassified (IBD-U)] who received upadacitinib plus another biologic for ≥4 months. Eligible patients had refractory IBD, defined as failure of ≥2 therapies with different mechanisms of action and active disease clinically or endoscopically. Primary outcome: clinical remission at 4 months. Secondary outcomes: clinical/endoscopic response, endoscopic remission during follow-up, and adverse events during treatment. Results: A total of 14 patients with refractory IBD were started on ACT (n = 10 females [71%]; n = 10 with CD [71%]), with a median disease duration of 7 years and a median follow-up of 8 months. All CD patients had Ilecolonic involvement, penetrating disease was present in (n = 6; 60%), and (n = 8; 80%) had perianal disease. Among UC patients (n = 4), 2 (50%) had pancolitis and 2 (50%) had left-sided colitis. The median number of prior advanced therapies was 2. At baseline, 62% had elevated C-reactive protein (CRP) and 93% had elevated fecal calprotectin (FCP). Endoscopic assessment revealed active disease in all patients. Ustekinumab was the most commonly used concurrent biologic with upadacitinib (n = 8; 57%), followed by vedolizumab (n = 4; 29%) and risankizumab (n = 2; 14%). Upadacitinib was initiated at a dose of 45 mg in most patients (n = 13; 93%); (n = 5; 36%) received a maintenance dose of 30 mg, while the remaining continued on 45 mg. At 4 months, (n = 5; 36%) achieved clinical remission, and (n = 6; 43%) showed a clinical response. Endoscopic data were available for 8 patients: (n = 2; 25%) achieved remission, (n = 2; 25%) showed a response, and (n = 4; 50%) had no endoscopic improvement. Two patients (n = 2; 14%) developed non-serious infections during ACT. One UC patient (7%) underwent colectomy for uncontrolled disease. Conclusion: ACT with upadacitinib and another biologic demonstrated promising clinical and endoscopic outcomes in refractory IBD and appeared to be well tolerated. Larger studies with longer follow-up duration are needed to further elucidate its long-term efficacy and safety.