Using Healthcare Databases to Replicate Trial Findings for Supplemental Indications: Adalimumab in Patients with Ulcerative Colitis.
Regulators wish to understand whether real-world evidence (RWE) can be used for secondary indications of biologics. Using the secondary indication of adalimumab for ulcerative colitis (UC) as an example, we aimed to replicate the ULTRA-2 RCT finding on the effectiveness of adalimumab in patients with UC using real world data analyses. Adalimumab, a TNF-alpha receptor inhibitor initially approved for Crohn’s disease, was approved for moderate to severe UC in 2012. The ULTRA-2 trial had shown improved remission against placebo in patients with UC. Using claims data (2006-2012), we conducted a cohort study of patients with UC who initiated adalimumab and compared them to 1) non-users and 2) new users of infliximab using propensity score matching. The co-primary endpoints were corticosteroid (CS) discontinuation within 8 weeks and 1 year of treatment. We computed hazard ratios (HR) and 95% confidence intervals (CIs). We identified 398 matched pairs of adalimumab users vs non-users and 326 pairs of adalimumab vs infliximab users. Adalimumab users were 28% more likely to achieve CS-discontinuation compared to non-users over 1 year (HR=1.28, 95% CI 0.94 to 1.73). However, unlike in ULTRA-2, this effect was not observed in the first 8 weeks (HR 0.79, 95% CI 0.65-0.97). Compared against infliximab, adalimumab initiators showed no incremental benefit over 1 year (HR=1.08; 0.80 to 1.04), but showed a 22% reduction (HR=0.78; 0.64-0.95) during the first 8 weeks of treatment. In summary, our results highlight opportunities and some limitations of database analysis to identify treatment effects for secondary indications.