Comparison of Switch to Fingolimod or Interferon Beta/Glatiramer Acetate in Active Multiple Sclerosis

Abstract

for the MSBase Study Group 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 PARTICIPANTSMatched 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 MEASURESAnnualized relapse rate and proportion of relapse-free patients, as well as the proportion of patients without sustained disability progression. RESULTSOverall, 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 RELEVANCESwitching 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.

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

“…Due to differences in study design and included populations, the results could not be meta-analysed and are reported narratively. Three of the studies were RCTs; 85,112,113 five were retrospective cohorts; [114][115][116][117][118] and one was a prospective cohort. 119 Before switching drugs, all participants had been receiving interferon beta-1a, interferon beta-1b or glatiramer acetate and were described as having had a treatment failure, although this term was not always defined 115,117 or was assessed subjectively by the neurologist.…”

“…In two of the trials, there was a high risk of performance and detection bias since all patients, providers and assessors were aware of treatment allocation, 85,113 whereas in the third trial, 112 the risk of bias was low since all participants, providers and assessors were blinded to treatment allocation. See Supplementary Appendix 4 - Table 37 for further details on the quality assessment.The cohort studies were assessed using the Cochrane tool for 'ROBINS-I', three were judged as having a moderate risk of bias 115,116,118 and three as having a serious risk of bias. 114,117,119 The domain that most commonly had a high risk of bias was in the measurement of outcomes, as outcome assessors were not blinded to participant treatment.…”

A 12-month, Open Label, Multicenter Pilot Study Evaluating Fingolimod Treatment in terms of Patient Satisfaction in Relapsing Remitting Multiple Sclerosis Patients - FINE Trial

“…Furthermore, large-scale studies in real-world settings showed that patients with RRMS who switched from injectable therapies to fingolimod had significantly lower rates of relapse or disability progression and also showed better treatment adherence than those who switched to other injectable treatments (17,18,19,20,21). Additional data exist suggesting that fingolimod is appropriate for patients who switch from natalizumab due to John Cunningham virus seroconversion, which causes progressive multifocal leukoencephalopathy and reduced response or tolerance (22,23).…”

Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis

“…There was also a significant decrease in treatment discontinuation among these patients (26). Another similar study from the MSBase Registry demonstrated that disability progression in patients switching from IFN β/glatiramer acetate to fingolimod treatment was 47% less compared with patients switching from another injectable treatment, and disability regression doubled when patients were switched to fingolimod (27).…”