“Critics of high drug costs frequently point out the costs of doing ‘unnecessary post-marketing studies‘ that Pharma do to position their products in the market. One could argue that the switch study below is an example of this. In short it shows if you are on an injectable (interferon-beta or glatiramer acetate) and you switch to fingolimod patient satisfaction, health-related quality of life, depression and fatigue severity improve. Does this tell you that fingolimod is better than interferon beta and/or glatiramer acetate? No, this was an open-label study and not designed as an efficacy study. To show superior efficacy you need to do a randomised, blinded (preferably double-blind), placebo-controlled trial. Do you think the sponsors of this study thought they were going to get a negative result? Absolutely not. If you don’t believe me read Ben Goldacre’s blog post ‘By me in the BMJ: the dodginess of drug company trials‘. Why then are these studies done? To nudge prescribers (neurologists) to change their prescribing behaviour. In other words these studies are done for the purpose of marketing. These types of studies don’t come cheap; I would love to know how much this study cost? Possibly $40-million? To put the latter in context I estimate fingolimod’s current annual sales to be closed to $3-billion, that is $3,000,000,000 per annum, which puts the costs of this trial in perspective.”
“Does the results of this study have any meaning for you as person with MS? Possibly, if you are on an injectable and are not tolerating the drug and or have breakthrough disease switching to fingolimod appears to be safe and relatively easy to do.”
BACKGROUND: The Evaluate Patient OutComes (ClinicalTrials.gov Identifier: NCT01216072) study was conducted in North America to assess patient- and physician-reported treatment satisfaction in patients with relapsing multiple sclerosis (MS) who received oral fingolimod for 6 months after switching from an injectable disease-modifying therapy (iDMT), without an intervening washout.
METHODS: In this open-label, multicenter study, patients were randomized 3:1 to once-daily fingolimod 0.5mg or iDMT. The primary study objective was to evaluate differences in satisfaction measured using the Treatment Satisfaction Questionnaire for Medication v1.4.
RESULTS: Of 1053 patients randomized, 790 patients received fingolimod and 263 patients received iDMT. Treatment satisfaction improved significantly in patients who switched to fingolimod compared with those who continued iDMT. Patients also reported significant improvements in health-related quality of life, reduced depression, and reduced fatigue severity after a switch to fingolimod. No difference between the treatment groups was detected on the Patient Reported Indices for MS Activities scale. The safety profile of fingolimod was consistent with that reported in the pivotal phase 3 studies. The most commonly reported adverse events were more prevalent in patients who switched to fingolimod than in those who continued iDMT (headache: 12% vs 3%; fatigue: 12% vs 6%). No significant relationship between lymphocyte counts and infection rates was observed and there was no evidence of additive immune-system effects, which might be expected when switching to a different class of immunomodulatory therapy with no intervening washout.
CONCLUSION: Patients who switched from iDMT to fingolimod had significant improvements in most self-reported outcomes compared with those who continued iDMT.
Hughes et al. First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis. Mult Scler Relat Disord. 2014;3(5):620-8.
BACKGROUND: In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients.
OBJECTIVE: We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier: NCT01216072).
METHODS: This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis, with subgroups of individuals who were receiving common concomitant HR-lowering medications or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose.
RESULTS: A transient decrease in mean HR and blood pressure occurred within 6h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%); eight patients reported dizziness and there was one case each of fatigue, palpitations, dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically mild or moderate in severity and all resolved spontaneously, without intervention or fingolimod discontinuation.
CONCLUSION: First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering medications were consistent with effects observed in the overall study population and with results from previous clinical trials. The EPOC study provides additional data demonstrating the transient and generally benign nature of fingolimod first-dose effects on HR and AV conduction in a large population that is more representative of patients encountered in routine clinical practice than in the pivotal trials.