Clin Gastroenterol Hepatol. 2022 Dec;20(12):2728-2740.e1.doi: 10.1016/j.cgh.2021.10.002. Epub 2021 Oct 8.

Joseph Meserve ¹, Christopher Ma ², Parambir S Dulai ¹, Vipul Jairath ³, Siddharth Singh ⁴

Author information

¹Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California.

²Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

³Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Division of Gastroenterology, Western University, London, Ontario, Canada.

⁴Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: sis040@ucsd.edu.

Abstract

Background & aims: Patients with Crohn's disease (CD) treated with ustekinumab who experience inadequate response, or loss of response after standard induction and/or maintenance dosing may benefit from dose escalation. We conducted a systematic review and meta-analysis examining the effectiveness of reinduction and/or dose interval shortening of ustekinumab in patients with active CD despite standard induction and maintenance.

Methods: Through a systematic literature search through March 31, 2021, we identified 15 cohort studies in 925 adults with CD with inadequate response or loss of response to standard dose ustekinumab, underwent dose escalation (reinduction and/or dose interval shortening to <8 weeks), and reported rates of achieving clinical response, corticosteroid-free clinical remission, endoscopic response, and/or remission. We calculated pooled rates (with 95% confidence intervals) using random effects meta-analysis and examined factors associated with response to dose escalation through qualitative synthesis of individual studies.

Results: On meta-analysis, 55% of patients (95% confidence interval, 52%-58%) with inadequate response or loss of response who underwent ustekinumab dose escalation achieved clinical response, with moderate heterogeneity (I² = 57%). Approximately 61% of patients were able to achieve endoscopic response, including 29% who achieved endoscopic remission. Dose interval shortening alone recaptured response in 57% patients. No consistent factors associated with response to dose escalation were identified on qualitative synthesis.

Conclusion: In real word settings, ustekinumab dose escalation was effective in achieving response in patients with CD with inadequate response, or loss of response to standard dose induction and/or maintenance therapy.