Risankizumab for Refractory Crohn’s Disease

Background: Risankizumab (RZB), a monoclonal antibody with high affinity to the P19 subunit of interleukin (IL)-23, has demonstrated efficacy in treating moderate to severe Crohn’s disease (CD). With its recent approval in June 2022, real-world results on the efficacy and appropriate positioning of RZB remain unclear. This study will analyze patients with refractory CD, who have failed 4 or more prior therapies, and are initiated on RZB. Methods: This retrospective study includes patients on RZB from Feb 2021 to May 2023 at an Inflammatory Bowel Disease (IBD) referral center. We illustrate patients’ prior biologic and small molecule therapies, past medical and surgical history, TPN and steroid usage, and disease severity. Laboratory results included: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and albumin, within 1 year before and after initiation of RZB. Clinical severity with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Severity-CD (SES-CD) was recorded from up to 1 year before and after initiation of RZB. Results: Cohort included twelve patients (4 male, 8 female), mean age of 42.8 years (range: 19-74), mean BMI 25.8 (range: 18.5-39.3) and a mean CD duration of 21.4 years (range: 2-40). All patients had failed multiple biologic or small molecule agents (range: 4-5). There were twelve different biologics and small molecules used in our study population prior to RZB initiation. This included: adalimumab (10), azathioprine (3), certolizumab (2), etanercept (1), golimumab (1), infliximab (9), mercaptopurine (2), methotrexate (3), tofacitinib (4), ustekinumab (9), upadacitinib (1), and vedolizumab (10). Mean duration of RZB therapy was 8.8 months (range: 4-26). Five patients had adjunct therapy with upadacitinib or vedolizumab, three required steroids and one was on TPN. Labs, prior to RZB initiation, included CRP (mean: 9.9, range: 0.3-31.9) and HBI score (mean: 10, range: 0-27). Post RZB initiation labs included CRP (mean: 3.4, range: 0.2-16) and HBI (mean: 5.2, range: 0-19). Nine subjects had an initial ESR (mean: 29.7, range: 2-86) and post RZB initiation ESR (mean: 16.1, range: 2-51). Two patients had an initial SES-CD score of 16 and 0, and after RZB initiation of 1 and 0 respectively. None experienced a drug related complication, 25% required disease related hospitalization and 25% required steroid usage during treatment period. Based off the HBI, five patients achieved clinical response defined as decrease in delta HBI > 3, six achieved clinical remission defined as an overall HBI < 5, and one did not respond. Conclusions: This study revealed a 50% clinical remission rate and 92% clinical response rate after starting therapy. A majority of patients with refractory CD did respond to RZB based off their HBI and change in inflammatory marker levels during the treatment period despite multiple biologic and small molecule failures making this a potential therapy in severe multi-drug resistant refractory CD patients.