Combination of Upadacitinib and Risankizumab in Refractory Crohn's Disease

ABSTRACT Background and Aim Dual targeted therapies (DTT) are a promising off‐label approach for the treatment of refractory Crohn's disease (CD). Upadacitinib and risankizumab are approved for the treatment of moderate to severe CD. Our aim was to evaluate the effectiveness and safety of a combination of upadacitinib and risankizumab for refractory CD. Methods In this retrospective, observational study we assessed n = 15 CD patients who received the combination upadacitinib and risankizumab at the Edinburgh IBD Unit, Scotland. All patients included had a minimum overlap of 8 weeks. The primary outcome was steroid‐free clinical response (SFCR) at 12 weeks defined as a decrease in Harvey Bradshaw Index (HBI) ≥ 3 and/or HBI < 5; if not available, a reduction of Physician Global Assessment (PGA) ≥ 1 was also considered as a response. Secondary outcomes included clinical remission (HBI < 5 or considered by PGA if HBI was not available), C‐reactive protein (CRP) remission (CRP≤ 5 mg/L) and faecal calprotectin (FC) remission (FC < 250 μg/g) at 12 weeks. Additional secondary outcomes were persistence at 24 and 52 weeks in patients with planned long‐term DTT, and successful withdrawal in patients with planned short‐term DTT. Safety outcomes were also recorded. Results Fifteen patients were included with a median of 3 prior advanced therapies (IQR 2–5). SFCR was achieved in 53% (8/15). Steroid‐free clinical remission, CRP and FC remission were achieved in 40% (6/15), 27% (4/15) and 27% (4/15) of the total patients, respectively. No treatment‐related serious adverse events were observed. Conclusions In this case series, combination upadacitinib and risankizumab demonstrated, short‐term effectiveness and safety in a highly refractory cohort of CD patients.