Real-World Outcomes in Fingolimod-Treated Patients with Multiple Sclerosis in the Czech Republic: Results from the 12-Month GOLEMS Study

Abstract

Background and ObjectiveOnce-daily oral fingolimod is approved in the EU as escalation treatment for adult patients with highly active relapsing multiple sclerosis (MS). The efficacy and safety profiles of fingolimod have been well established in a large clinical development programme and several papers reflecting the experience with fingolimod in real-world settings have been published to date. The GOLEMS study was designed to evaluate the efficacy, safety and tolerability of fingolimod and the impact of fingolimod treatment on disability progression and work capability in patients with MS in routine clinical practice in the Czech Republic.MethodsGOLEMS was a national, multicentre, non-interventional, single-arm study conducted to analyse the outcomes of a minimum of 12 months of fingolimod therapy on primary and secondary endpoints. The primary endpoint was to assess the proportion of relapse-free patients and severity of MS relapses in patients treated with fingolimod for 12 months. Secondary endpoints included assessment of changes in disability progression evaluated by the Expanded Disability Status Scale (EDSS) score and work capability assessment measured through voluntary completion of the WPAI-GH questionnaire. The predictive factors for relapse-free status during fingolimod treatment were also analysed.ResultsOf the 240 enrolled patients, 219 completed the 12-month treatment period at the time of final analysis. In the efficacy set (N = 237), the proportion of relapse-free patients increased from 47 patients (19.6 %; 95 % confidence interval [CI] 14.8–25.2) in the year before fingolimod initiation to 152 patients (64.1 %; 95 % CI 58.0–70.2) after 1 year of fingolimod treatment. Of the 85 patients who experienced at least one relapse after 1 year of fingolimod treatment, 53 (62.4 %; 95 % CI 51.7–71.9) reported only one relapse, while 25 (29.4 %; 95 % CI 20.8–39.8) and seven (8.2 %; 95 % CI 4.0–16.0) patients had ≥2 relapses, respectively. No significant changes were observed in EDSS scores over the 12-month treatment period compared with baseline. The absolute number of relapses during 2 years before initiation of fingolimod treatment and baseline EDSS scores were identified as significant independent predictors for ‘being relapse-free’ during the 12-month fingolimod treatment period. No trend was established in work capability or number of missed days at work due to the large proportion of missing data. Of 240 enrolled patients, 27 (11.3 %) patients discontinued the study at or before the 12-month visit, 16 (6.7 %) discontinued because of adverse events related to study drug. Only six (2.5 %) patients reported serious adverse events related to the study drug.ConclusionThe results confirm the favourable safety and efficacy profile of fingolimod under real-world conditions, consistent with phase III trials.

REALMS study: real-world effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis in Portugal

“…In our population, and similar to other studies [11,15,18,19,30], fingolimod has shown to have a good safety profile. The proportion of patients discontinuing treatment was mostly related to disease activity (5.5%).…”

“…These attrition rates are similar to the ones found in the present study (9.8%), which are also similar to the ones reported by the real-word study with fingolimod from UK (approximately 8%) [13]. In other two real-world studies, one conducted in the Czech Republic, the GOLEMS study, 11.3% of patients discontinued fingolimod at N, number of patients; %, percentage of total; ULN, upper limit of normal a Three opportunistic infections, one hepatic enzymes > 3 × ULN and one disease activity could not be assigned to a specific year given the dates are lacking or before 12 months [19] and another one conducted in Spain, the MS NEXT, 3.9% of patients permanently discontinued fingolimod during the first year of treatment [20]. Overall, the proportion of relapse-free patients significantly increased from 78.9 to 90.5% from the first to the third year after switching to fingolimod therapy.…”

Extended treatment with fingolimod for relapsing multiple sclerosis: the 14-year LONGTERMS study results

“…The overall pattern of AEs or SAEs reported with long-term fingolimod treatment was similar to those reported in the feeder studies, 8–12 and from real-world studies. 13–19 In line with those previous studies, the most commonly reported AEs were headache, lymphopenia, and influenza, all of which showed a clear decreasing trend from year 1 to year 11 in LONGTERMS. In addition to selective drop out in the feeder studies, such a decrease in reported AEs could be due to reduced reporting by the investigators or patients who had adapted to recurring similar AEs.…”

“…Fingolimod (FTY720, Gilenya®), a sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral DMT approved for the treatment of relapsing MS (RMS), 5–7 after efficacy and safety were demonstrated in pivotal phase III clinical trials against placebo (FREEDOMS, 8 FREEDOMS II 9 ) and interferon (IFN) beta-1a (TRANSFORMS). 10 First reports from extension studies 11,12 and from the use of fingolimod in real-world settings across different geographical regions 13–19 were consistent with the results of the pivotal studies. However, as for other DMTs, longer-term data on safety and efficacy of fingolimod are needed to optimize treatment strategies for MS disease management in routine clinical practice.…”

A randomized study to evaluate the effect of exercise on fatigue in people with relapsing–remitting multiple sclerosis treated with fingolimod

“… 44 Reports from observational studies with an observational period of 12 months give AE incidence rates of 35% to 60%. 45 , 46 Noteworthy is that no participant reported any cardiovascular adverse event during the six-month study period. The proportion of relapse-free PwMS during the study period was about 90% in both groups.…”