Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

PLoS One. 2013 May 21;8(5):e63480. doi: 10.1371/journal.pone.0063480. Print 2013.

Abstract

Objectives: To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics.

Methods: Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded.

Results: Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages.

Conclusions: Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Demography
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interferon beta-1a
  • Interferon-beta / administration & dosage*
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use*
  • Kaplan-Meier Estimate
  • Likelihood Functions
  • Magnetic Resonance Imaging
  • Male
  • Medication Adherence*
  • Multiple Sclerosis / drug therapy*
  • Propensity Score*
  • Reproducibility of Results
  • Treatment Outcome
  • Withholding Treatment

Substances

  • Interferon-beta
  • Interferon beta-1a

Grants and funding

This study was funded by MSBase Foundation, a not-for-profit organisation. The MSBase Foundation receives financial support from Merck Serono, Biogen Idec, Novartis Pharma, Bayer Schering and Sanofi Aventis. The study was also funded by Multiple Sclerosis Research Australia and MSAngels. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.