S1164 Head-to-Head Comparison of Biologics vs Ustekinumab for Crohn’s Disease: A Systematic Review of Efficacy

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Introduction: Numerous treatments have been emerging in the field of Inflammatory bowel disease (IBD) with various therapeutic targets being explored to achieve clinical and endoscopic remission in patients. Drugs targeting Interleukin 12/23 such as Ustekinumab have shown promising results for Crohn’s disease. However, there have been only a few trials comparing 1 biologic with another. Here we aim to consolidate the clinical and endoscopic efficacy data of various biologics in comparison with Ustekinumab. Methods: We performed a systematic review of literature databases like Pubmed, Cochrane, Embase, clinical trials.gov and google scholar from January 2020 to May 2024. Data pertaining to drug dose, frequency, induction/maintenance information, clinical outcomes and adverse events were interpreted using descriptive analysis. Results: A total of 4 phase - 3 trials comparing various biologics with Ustekinumab were included this study - SEAVUE (adalimumab), SEQUENCE (risankizumab), VIVID-1(mirikizumab) and GALAXI 2 and 3 (guselkumab). The endpoints reviewed include - Clinical remission, endoscopic remission and endoscopic response. In terms of Clinical remission, mirikizumab (54.10% vs 48.40%, p 0.113) and guselkumab (70.30% vs 62.90%, p 0.058) were more effective than Ustekinumab. On the other hand, adalimumab had lesser efficacy than ustekinumab (61% vs 64.90%, p 0.417). Although these differences were numerically significant, they did not meet statistical significance. In terms of endoscopic remission and response, guselkumab achieved statistically significant remission ((37.2% vs 24.70%) and response (52.70% vs 37.10%) compared to ustekinumab. Risankizumab also attained statistically significant endoscopic remission compared to ustekinumab at wk 48 (31.80% vs 16.20%) Conclusion: To our knowledge, this is the first ever study reviewing the head-to-head comparison trials of various biologics in Crohn’s disease. We noticed that guselkumab and risankizumab showed superior outcomes compared to ustekinumab for Crohn’s disease. Real world data comparing biologics with each other are warranted to validate this clinical data (see Table 1). Table 1. - Clinical and Endoscopic outcomes of biologics vs ustekinumab Endpoint Comparison Biologic % Ustekinumab % p value Clinical Remission Mirikizumab 54.10% 48.40% 0.113 Risankizumab - - - Adalimumab 61% 64.90% 0.417 Guselkumab 70.30% 62.90% 0.058 Endoscopic Remission Mirikizumab 28.50% 27.90% 0.852 Risankizumab 31.80% 16.20% < 0.0001 Adalimumab 30.70% 28.50% 0.631 Guselkumab 37.20% 24.70% 0.001 Endoscopic Response Mirikizumab 48.40% 46.30% 0.513 Risankizumab - - - Adalimumab 36.90% 41.90% 0.349 Guselkumab 52.70% 37.10% < 0.001

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