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Using Healthcare Databases to Replicate Trial Findings for Supplemental Indications: Adalimumab in Patients with Ulcerative Colitis.

Authors
  • Spoendlin, Julia1
  • Desai, Rishi J1
  • Franklin, Jessica M1
  • Glynn, Robert J1
  • Payne, Emma2
  • Schneeweiss, Sebastian1
  • 1 Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  • 2 Aetion Inc., Boston, Massachusetts, USA.
Type
Published Article
Journal
Clinical Pharmacology & Therapeutics
Publisher
Wiley (Blackwell Publishing)
Publication Date
Oct 01, 2020
Volume
108
Issue
4
Pages
874–884
Identifiers
DOI: 10.1002/cpt.1861
PMID: 32320482
Source
Medline
Language
English
License
Unknown

Abstract

Regulators wish to understand whether real world evidence 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 randomized controlled trial finding on the effectiveness of adalimumab in patients with UC using realworld 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 with (i) nonusers and (ii) new users of infliximab using propensity score matching. The coprimary end points were corticosteroid (CS) discontinuation within 8 weeks and 1 year of treatment. We computed hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 398 matched pairs of adalimumab users vs. nonusers and 326 pairs of adalimumab vs. infliximab users. Adalimumab users were 28% more likely to achieve CS-discontinuation compared with nonusers over 1 year (HR = 1.28; 95% CI 0.94-1.73). 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 with infliximab, adalimumab initiators showed no incremental benefit over 1 year (HR = 1.08; 95% CI 0.80-1.04), but showed a 22% reduction (HR = 0.78; 95% CI 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. © 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.

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