Comparison of Switch to Fingolimod or Interferon beta/glatiramer Acetate in Active Multiple Sclerosis

JAMA Neurol. 2015 Apr;72(4):405-13. doi: 10.1001/jamaneurol.2014.4147.

Abstract

Importance: After multiple sclerosis (MS) relapse while a patient is receiving an injectable disease-modifying drug, many physicians advocate therapy switch, but the relative effectiveness of different switch decisions is often uncertain.

Objective: To compare the effect of the oral immunomodulator fingolimod with that of all injectable immunomodulators (interferons or glatiramer acetate) on relapse rate, disability, and treatment persistence in patients with active MS.

Design, setting, and participants: Matched retrospective analysis of data collected prospectively from MSBase, an international, observational cohort study. The MSBase cohort represents a population of patients with MS monitored at large MS centers. The analyzed data were collected between July 1996 and April 2014. Participants included patients with relapsing-remitting MS who were switching therapy to fingolimod or injectable immunomodulators up to 12 months after on-treatment clinical disease activity (relapse or progression of disability), matched on demographic and clinical variables. Median follow-up duration was 13.1 months (range, 3-80). Indication and attrition bias were controlled with propensity score matching and pairwise censoring, respectively. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity analyses were conducted.

Exposures: Patients had received fingolimod, interferon beta, or glatiramer acetate for a minimum of 3 months following a switch of immunomodulatory therapy.

Main outcomes and measures: Annualized relapse rate and proportion of relapse-free patients, as well as the proportion of patients without sustained disability progression.

Results: Overall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. The fingolimod group had a lower mean annualized relapse rate (0.31 vs 0.42; 95% CI, 0.02-0.19; P=.009), lower hazard of first on-treatment relapse (hazard ratio [HR], 0.74; 95% CI, 0.56-0.98; P=.04), lower hazard of disability progression (HR, 0.53; 95% CI, 0.31-0.91; P=.02), higher rate of disability regression (HR, 2.0; 95% CI, 1.2-3.3; P=.005), and lower hazard of treatment discontinuation (HR, 0.55; P=.04) compared with the injectable group.

Conclusions and relevance: Switching from injectable immunomodulators to fingolimod is associated with fewer relapses, more favorable disability outcomes, and greater treatment persistence compared with switching to another injectable preparation following on-treatment activity of MS.

Publication types

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

MeSH terms

  • Adult
  • Cohort Studies
  • Female
  • Fingolimod Hydrochloride
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Interferon-beta / administration & dosage
  • Interferon-beta / therapeutic use*
  • Magnetic Resonance Imaging / methods
  • Male
  • Multiple Sclerosis / drug therapy*
  • Propylene Glycols / administration & dosage
  • Propylene Glycols / therapeutic use*
  • Retrospective Studies
  • Sphingosine / administration & dosage
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Treatment Outcome

Substances

  • Immunologic Factors
  • Immunosuppressive Agents
  • Propylene Glycols
  • Interferon-beta
  • Fingolimod Hydrochloride
  • Sphingosine