Abstract Background Guselkumab (GUS), a selective IL-23p19 inhibitor, was recently approved for Crohn’s disease (CD). Real-world data on patients switching within the IL-23 class are scarce. We aimed to evaluate the effectiveness, safety, and treatment persistence of GUS in a refractory cohort previously exposed to risankizumab (RISA), to inform biologic sequencing after IL-23 inhibitor failure. Methods We prospectively monitored all patients started on GUS at weeks 0, 2, 4, 8, and 12 to capture disease activity using the Harvey-Bradshaw index (HBI), steroid use, adverse events, and laboratory results (C-Reactive Protein (CRP) and fecal calprotectin (FCP)). Patients with ≥8 weeks of therapy were analyzed. Data were abstracted from the medical records, including prior RISA exposure (start/stop dates, duration, maintenance interval, dose intensification, and reason for discontinuation) and therapies administered between RISA and GUS. Baseline demographics, IBD phenotype, prior surgery, and prior biologic classes were recorded. Results Twenty-eight patients with CD (75% female, mean age 50.8 ± 14.9 years, disease duration 21.2 ± 11.8 years) were included in the study. Baseline characteristics were stricturing phenotype in 54%, ileocolonic location in 48%, and 71% had a history of previous surgery. 89% had ≥3 advanced therapies, and 71% had prior JAK inhibitor treatment. The mean duration of RISA therapy was 15.4 ± 10.4 months. Reasons for RISA discontinuation included secondary non-response (loss of response) (53.6%), primary non-response (21.4%), and adverse events (10.7%). (Table) At baseline, the median Harvey-Bradshaw Index (HBI) was 5 (interquartile range IQR 3-8), and median FCP was 653 μg/g IQR 99.9-1138.8. HBI scores decreased to 4 (IQR 2-6) at week 8 and further to 2.5 (IQR 0-5) at week 12. (Figure) The rates of steroid-free remission increased from 35.7% at baseline to 68.2% at week 12. Among patients with active disease at baseline (n = 11), the median HBI decreased from 9 (QR 7.5-10.5 to 5 QR 1-7 at week 12. The median FCP decreased from 653.5 μg/g (IQR 82.3-552.8) to 165.5 μg/g (IQR 82.3- 552.8) at week 12. Changes in C-reactive protein (CRP) were not statistically significant over time. Univariate analysis revealed no significant associations between age, sex, disease duration, prior biologic therapies, reasons for RISA discontinuation, or baseline inflammatory markers and steroid-free clinical remission. There were no treatment emergent adverse events. Conclusion Treatment with GUS was effective and safe in a complex group of patients with CD who previously have been exposed to RISA, many of whom were primary or secondary non-responders. Further study of the potential for such in class cycling is warranted. Conflict of interest: Shafrir, Asher: No conflict of interest Ayoub, Malek: No conflict of interest Mr. Mathew, Alex: No conflict of interest Tanouye, Jessica M: No conflict of interest Hannett, Alexandra R: No conflict of interest Choi, David: D.C. has served on the speaker bureau for Janssen Pharmaceuticals, AbbVie, Eli Lilly and as a Consultant for Bristol Myers Squibb, Boehringer Ingelheim, AbbVie, Eli Lilly, Janssen Pharmaceuticals, and Pfizer Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx.
Shafrir et al. (Thu,) studied this question.