OBJECTIVES: We conducted a systematic literature review to identify randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for Crohn’s disease (CD).
METHODS: Literature searches were conducted in six databases (including MEDLINE, Embase, and Cochrane databases) on August 25, 2022, without geographic, language, or date restrictions. Additional searches were conducted in conference proceedings, regulatory websites, trial registries, and bibliographies. Records were screened by two independent reviewers to identify phase 2–4 RCTs of prespecified advanced therapies in adults with moderate to severe CD. Data were extracted from eligible studies reporting at least one prespecified outcome of interest. Study quality was assessed using the Cochrane Risk of Bias tool.
RESULTS: Data for 51 RCTs were extracted from 240 records. Half of the studies (N = 26) were double-blind, multinational, phase 3 RCTs. Mean patient age (28–47 years), disease duration (1–16 years), and CD activity index (CDAI) score (88–364) varied across studies, as well as the proportion of men (0–87%), and patients with a history of fistulizing disease (0–100%). Clinical remission was the most reported efficacy outcome, defined as a CDAI score ≤ 150, although six studies used additional definitions based on stool frequency and abdominal pain scores. The Inflammatory Bowel Disease Questionnaire was the most reported health-related quality of life outcome. Overall, study quality was good, despite uncertainty in some quality domains.
CONCLUSIONS: The use of CDAI to measure efficacy was common among the studies; however, variability in baseline characteristics and timing of outcome measurements presents challenges in generating strong comparative evidence. Further analyses are needed to determine whether these differences can be addressed quantitatively and provide insight into the comparative efficacy of advanced therapies for CD. An emerging trend was observed for the inclusion of patient-reported outcomes in the clinical remission definition.
