Phase IV study of retention on fingolimod versus injectable multiple sclerosis therapies: a randomized clinical trial

Abstract

Objective:In relapsing–remitting multiple sclerosis (RRMS), suboptimal adherence to injectable disease-modifying therapies (iDMTs; interferon β-1a/b, glatiramer acetate) is common, reducing their effectiveness. Patient retention on oral fingolimod and iDMTs was evaluated in PREFERMS, a randomized, parallel-group, active-controlled, open-label, 48-week study.Methods:Patients were included if they had RRMS, were aged 18–65 years and had Expanded Disability Status Scale score up to 6, enrolled at 117 US study sites, were treatment naïve or had received only one iDMT class. Patients were randomized 1:1 (fingolimod 0.5 mg/day; preselected iDMT) by interactive voice-and-web-response system without blinding, followed up quarterly, and allowed one study-approved treatment switch after 12 weeks, or earlier for efficacy or safety reasons. The primary outcome was patient retention on randomized treatment over 48 weeks. Secondary endpoints included patient-reported outcomes, brain volume loss (BVL), and cognitive function.Results:Analysis of 433/436 patients receiving fingolimod and 428/439 receiving iDMTs showed that patient retention rate was significantly higher with fingolimod than with iDMTs [352 (81.3%) versus 125 (29.2%); 95% confidence interval 46.4–57.8%; p < 0.0001]. The most common treatment switch was from iDMT to fingolimod for injection-related reasons. Patient satisfaction was greater and BVL less with fingolimod than with iDMTs, with no difference in cognitive function. Adverse events were consistent with established tolerability profiles for each treatment.Conclusions:In RRMS, fingolimod was associated with better treatment retention, patient satisfaction and BVL outcomes than iDMTs. Patients may persist with iDMTs, but many may switch treatment if permitted. Treatment satisfaction fosters adherence, a prerequisite for optimal outcomes.

The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta‐analysis

“…Our result has been supported by the LONGTERMS trial, an open‐label, single‐arm, long‐term extension study ( n = 2355) in which the results demonstrated that low rates of brain volume loss were sustained for up to 6 years of fingolimod treatment . All the three trials that compared fingolimod with DMTs used the dose of 0.5 mg/d, and fingolimod was found to be more effective than DMTs.…”

“…Of 1495 publications returned from the literature search, ten studies with a total of 6547 patients met the inclusion criteria. The selection process is depicted in the flow diagram (Figure ).…”

“…The dose of fingolimod ranged from 0.5 to 5 mg/d. All studies reported adverse drug reactions and 6 of them reported the ARR . The majority of trials were blinded appropriately to avoid performance and detection bias.…”

“…However, no remarkable difference was detected in the 5 mg/d subgroup (Figure S3). Compared with DMTs, there was a substantial significance in the percentage change of brain volume (MD = 0.16; 95% CI: 0.09 to 0.23; I 2 = 0%; P < .0001; Figure ).…”

“…Of 1495 publications returned from the literature search, ten studies 20-29 with a total of 6547 patients met the inclusion criteria. The selection process is depicted in the flow diagram [20][21][22][23][24][25] The majority of trials were blinded appropriately to avoid performance and detection bias. We considered the methods of allocation concealment to be at an unclear risk of bias in six trials 20,23,25,26,28,29 , and we judged one trial 27 to be at high risk of bias.…”