Using Healthcare Databases to Replicate Trial Findings for Supplemental Indications: Adalimumab in Patients with Ulcerative Colitis.
Adalimumab
/ adverse effects
Adult
Colitis, Ulcerative
/ drug therapy
Databases, Factual
Evidence-Based Medicine
Female
Humans
Infliximab
/ adverse effects
Male
Middle Aged
Randomized Controlled Trials as Topic
Remission Induction
Time Factors
Treatment Outcome
Tumor Necrosis Factor Inhibitors
/ adverse effects
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
24
01
2020
accepted:
06
04
2020
pubmed:
23
4
2020
medline:
25
5
2021
entrez:
23
4
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Tumor Necrosis Factor Inhibitors
0
Infliximab
B72HH48FLU
Adalimumab
FYS6T7F842
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
874-884Informations de copyright
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Références
US Food and Drug Administration. Framework for FDA’s real-world evidence program <https://www.fda.gov/media/120060/download> (2018). Accessed October 31, 2019.
Berger, M.L. et al. Good practices for real-world data studies of treatment and/or comparative effectiveness: recommendations from the joint ISPOR-ISPE special task force on real-world evidence in health care decision making. Value Health 20, 1003-1008 (2017).
Franklin, J.M., Glynn, R.J., Martin, D. & Schneeweiss, S. Evaluating the use of nonrandomized real-world data analyses for regulatory decision making. Clin. Pharmacol. Ther. 105, 867-877 (2019).
Franklin, J. & Schneeweiss, S. When and how can real world data analyses substitute for randomized controlled trials? Clin. Pharmacol. Ther. 102, 924-933 (2017).
Fralick, M., Kesselheim, A.S., Avorn, J. & Schneeweiss, S. Use of health care databases to support supplemental indications of approved medications. JAMA Intern. Med. 178, 55-63 (2018).
Berndt, E.R., Cockburn, I.M. & Grépin, K.A. Biopharmaceuticals drug utilisation in original and supplemental indications. Pharmacoeconomics 2, 69-86 (2006).
Sandborn, W.J. et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 142, 257-265.e3 (2012).
Schneeweiss, S. A basic study design for exedited safety signal evaluation based on electronic healthcare data. Pharmacoepidemiol. Drug Saf. 19, 858-868 (2010).
Hansen, L.G. & Chang, M.S.White Paper - Health research data for the real world: the MarketScan databases; Published By Truven Health Analytics <http://truvenhealth.com/portals/0/assets/PH_11238_0612_TEMP_MarketScan_WP_FINAL.pdf> (2011). Accessed October 31, 2019.
Schroeder, K., Tremaine, W. & Ilstrum, D. Coated Oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N. Engl. J. Med. 317, 1625-1629 (1987).
Sandborn, W. Adalimumab in the treatment of moderate-to-severe ulcerative colitis: ULTRA 2 trial results. Gastroenterol. Hepatol. (NY). 9, 317-320 (2013).
Sany, J. Study of the tolerance of infliximab infusions with or without betamethasone premedication in patients with active rheumatoid arthritis. Ann. Rheum. Dis. 64, 1647-1649 (2005).
Franklin, J.M., Rassen, J.A., Ackermann, D., Bartels, D.B. & Schneeweiss, S. Metrics for covariate balance in cohort studies of causal effects. Stat. Med. 33, 1685-1699 (2014).
Wang, S.V., Verpillat, P., Rassen, J.A., Patrick, A., Garry, E.M. & Bartels, D.B. Transparency and reproducibility of observational cohort studies using large healthcare databases. Clin. Pharmacol. Ther. 99, 325-332 (2016).
Thorlund, K., Druyts, E., Mills, E.J., Fedorak, R.N. & Marshall, J.K. Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naive to anti-TNF therapy: an indirect treatment comparison meta-analysis. J. Crohns Colitis 8, 571-581 (2014).
Desai, R.J., Rothman, K.J., Bateman, B.T., Hernandez-Diaz, S. & Huybrechts, K.F. A propensity score based fine stratification approach for confounding adjustment when exposure is infrequent. Epidemiology 28, 1 (2016).
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ICH Harmonised Guideline. ICH Harmonised Guidelines. Addendum on Estimands and Sensitivity Analysis in Clinical Trials (2019). <https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf>.
Steiner, J.F. & Prochazka, A.V. The assessment of refill compliance using pharmacy records: methods, validity, and applications. J. Clin. Epidemiol. 50, 105-116 (1997).
Wolf, D. et al. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severely active ulcerative colitis. Aliment Pharmacol. Ther. 40, 486-497 (2014).
Stidham, R.W. et al. Alimentary pharmacology and therapeutics systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Aliment Pharmacol. Ther. 39, 660-671 (2014).
Elze, M.C. et al. Comparison of propensity score methods and covariate adjustment: evaluation in 4 cardiovascular studies. J. Am. Coll. Cardiol. 69, 345-357 (2017).
Glynn, R.J., Schneeweiss, S. & Stürmer, T. Indications for propensity scores and review of their use in pharmacoepidemiology. Basic Clin. Pharmacol. Toxicol. 98, 253-259 (2006).
Samuel, M., Schuster, T., Kaufman, J.S., Platt, R.W. & Brophy, J.M. Differences between conditional and marginal propensity score estimates: a real-world application. J. Am. Coll. Cardiol. 70, 117 (2017).
Hade, E. & Lu, B. Bias associated with using the estimated propensity score as a regression covariate. Stat. Med. 33, 74-87 (2014).
Wasserstein, R.L. & Lazar, N.A. The ASA’s statement on p-values: context, process, and purpose. Am. Stat. 70, 129-133 (2016).