Abstract Background Inflammatory bowel disease management has evolved in recent years, with the emergence of new biotherapies such as risankizumab,(RZB) an interleukin (IL) 23 p19 inhibitor, with demonstrated efficacy in moderate-to-severe Crohn’s disease. While the relationship between trough levels and clinical remission is well established for anti-TNF alpha agents, it has yet to be demonstrated for new molecules of interest. The aim of this study was to investigate the correlation between RZB trough levels and clinical and biological remission at 6, 12 and 18 months. Methods This retrospective multicenter study included patients with moderate-to-severe Crohn’s disease from 4 centers, who were being treated with RZB after failure of all other approved biotherapy lines. Clinical activity, assessed by the Harvey-Bradshaw Index (HBI) and biological activity with CRP and fecal calprotectin, as well as serum RZB levels by Elisa technique (Biosynex) were collected. The primary endpoint was clinical and biological remission at 12 months, defined as HBI < 4, CRP < 5 mg/L and fecal calprotectin < 250 µg/g of stool. Secondary objectives were the correlation between RZB levels and clinical and biological remission at 6 and 18 months, treatment persistence, and safety. Results Overall, 43 patients were included in 4 centers. Most patients had ileocolic Crohn’s disease (44.7%), 50% had ano-perineal lesions, 23.7% had extra-intestinal manifestations and 71.7% had a history of bowel resection. Six patients (15.8%) were receiving a combination of advanced therapies with upadacitinib or golimumab. At 12 months, 30.2% of patients were in clinical and biological remission (n=13) and had significantly higher RZB trough levels than patients who were not in remission (8.26 ± 4.66 vs. 4.44 ± 2.37 respectively; p=0.002). The ROC curve identified an optimal risankizumab trough levels threshold of 7.7 µg/mL for predicting clinical and biological remission at 12 months (sensitivity 61.5%; specificity 92%). At 6 and 18 months, 11.7% (n=5) and 34.9% (n=15) of patients were in clinical remission and had significantly higher RZB trough levels. At 6 months, 12 months and 18 months, 43 (100%), 38 (88.4%) and 31 (72%) patients were still on RZB. No patient developed anti-risankizumab antibodies. Conclusion In our multicenter study, with the largest number of patients analyzed to date, trough levels of risankizumab were correlated with clinical and biological response at 12 months in patients with moderate-to-severe Crohn’s disease, in line with data from previous single-center studies but larger prospective studies are still needed.
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