Dual-targeted therapy with risankizumab and upadacitinib in medically complex Crohn's disease

There are significant unmet needs for the treatment of Crohn's disease (CD). We have previously described a novel dual-targeted therapy (DTT) of the interleukin-12/23 (IL-12/23) inhibitor ustekinumab and selective Janus kinase 1 inhibitor upadacitinib (UPA). Here, we evaluate the safety and effectiveness of the IL-23 inhibitor risankizumab (RISA) combined with UPA in patients with CD.

We retrospectively analyzed data from our prospectively collected real-world database of patients with CD at the [Institution Name] treated with the combination of RISA and UPA from November 05, 2021 to September 18, 2024. Clinical response and remission, extraintestinal manifestation outcomes, and adverse events were evaluated in all patients, including ileostomy patients.

Nineteen patients with CD were treated with RISA and UPA (median age 38 years [interquartile range, IQR 33.5-43.5], 13/19 [68%] female, median disease duration at DTT initiation 14.1 years [IQR 10.9-22.8], 14/19 [73.7%] had prior inflammatory bowel disease [IBD] surgeries, 5/19 [26.3%] had ileostomies). At DTT initiation, most patients had been treated previously with more than 4 prior advanced therapies (median 5, IQR 4-6). Among patients with clinically active disease at baseline, 5/7 (71.4%) achieved clinical remission and 2/7 (28.6%) achieved clinical response without remission. All 4 ileostomy patients with active disease responded, and 2 achieved clinical remission. Eight patients had active EIMs at baseline; 7/8 (87.5%) improved, with 4 achieving resolution. Three patients discontinued DTT due to adverse events (acne [1], fatigue [1], and upper respiratory infection [1]).

DTT with RISA and UPA is effective and safe in medically resistant CD.