Combining Guselkumab with Upadacitinib Is Safe and Effective in the Treatment of Medically Complex Inflammatory Bowel Disease

BACKGROUND AND AIMS: Dual-targeted therapy (DTT) combines medications with different anti-inflammatory mechanisms to manage immune-mediated conditions. We describe our experience of adding guselkumab (GUS) to upadacitinib (UPA) in complex inflammatory bowel disease (IBD). METHODS: We reviewed our real-world registry of adult patients with IBD who had GUS added to UPA. Prospectively collected outcomes included clinical remission (Harvey-Bradshaw Index (HBI) < 5 or Simple Clinical Colitis Activity Index (SCCAI) < 3), biochemical remission (normalization of fecal calprotectin (FCP)/CRP), corticosteroid-free remission, and adverse events (AEs). Patient-reported activity of extraintestinal manifestations (EIMs) was retrospectively reviewed. RESULTS: We identified 11 patients with Crohn's disease (CD) and 4 with ulcerative colitis (UC) who added GUS to UPA for luminal inflammation (n = 12) and/or EIMs (n = 5). Five of nine patients with active CD achieved biochemical remission. Of the four with symptomatic CD (HBI > 5), two achieved clinical remission. Four patients received DTT for CD-associated EIMs and two had partial improvement of symptoms after GUS. All 3 patients who started DTT for active UC achieved clinical remission and one with active enteropathic arthropathy had partial improvement of symptoms after DTT. AEs included minor skin irritation, fatigue, and headaches. 14/15 patients remain on DTT after median 6 months' follow-up. CONCLUSION: The addition of GUS to UPA led to clinical remission in 50% and 100% of patients with CD and UC, and biochemical remission in 55.6% and 66.7% of patients with CD and UC, respectively. 60% noted improvement of their EIMs after adding GUS. No serious AEs were reported highlighting the safety of this DTT strategy.