A Systematic Review on Long-Term Efficacy Outcome Measures in Crohn's Disease Patients

Laura M Janssen; Rob H Creemers; Adriaan A van Bodegraven; Marie J Pierik

doi:10.1093/ecco-jcc/jjad037

A Systematic Review on Long-Term Efficacy Outcome Measures in Crohn's Disease Patients

J Crohns Colitis. 2023 Oct 20;17(9):1528-1536. doi: 10.1093/ecco-jcc/jjad037.

Authors

Laura M Janssen^{1

2}, Rob H Creemers^{1

3}, Adriaan A van Bodegraven³, Marie J Pierik^{1

2}

Affiliations

¹ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
² School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, Maastricht, The Netherlands.
³ Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Centre, Heerlen-Sittard-Geleen, The Netherlands.

Abstract

Background: The traditional long-term treatment goal of Crohn's disease [CD] is maintenance of corticosteroid-free clinical remission. Additional treatment targets, such as biochemical, endoscopic and patient-reported remission, are advocated. The relapsing-remitting nature of CD provides a challenge to the timing of target assessment. Cross-sectional assessment at predetermined moments disregards the health state in between measurements. In this systematic review, we provide an overview of outcomes used to assess long-term efficacy in clinical trials in CD.

Methods: A systematic search of the PubMed and EMBASE databases was performed to identify clinical trials in luminal CD reporting on maintenance treatment [strategies] since 1995. Two independent reviewers selected eligible articles for full text retrieval, and assessed if long-term corticosteroid-free clinical, biochemical, endoscopic or patient-reported efficacy outcomes were used.

Results: The search resulted in 2452 hits and 82 articles were included. Clinical activity was used in 80 studies [98%] as the long-term efficacy outcome, and in 21 [26%] of these concomitant corticosteroid use was taken into account. C-reactive protein was used in 32 studies [41%], faecal calprotectin in 15 studies [18%], endoscopic activity in 34 studies [41%] and patient-reported outcome in 32 studies [39%]. In seven studies, clinical, biochemical, endoscopic activity and the patient's perspective were measured. In most studies cross-sectional measures or multiple measurements over time were used.

Conclusion: In none of the published clinical trials in CD was sustained remission on all treatment targets reported. Cross-sectional outcomes at predetermined times were widely applied, leading to lack of information regarding sustained corticosteroid-free remission for this relapsing-remitting chronic disease.

Keywords: Crohn’s disease; clinical trial; outcome measures; sustained remission.