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

Clin Drug Investig (2017) 37:175–186 DOI 10.1007/s40261-016-0471-2 ORIGINAL RESEARCH ARTICLE Real-World Outcomes in Fingolimod-Treated Patients with Multiple Sclerosis in the Czech Republic: Results from the 12-Month GOLEMS Study Veronika Tichá1 • Roman Kodým2 • Zuzana Počı́ková2 • Pavla Kadlecová3 Published online: 26 October 2016 Ó The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Background and Objective Once-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. Methods GOLEMS 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 & Veronika Tichá 1 MS Center, Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine and General University Hospital in Prague, Charles University, Katerinska 30, 120 00 Prague, Czech Republic 2 Novartis s.r.o., Na Pankraci 1724/129, 14000 Prague, Czech Republic 3 Aprova s.r.o., Brno, Czech Republic 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. Results Of 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 C2 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. Conclusion The results confirm the favourable safety and efficacy profile of fingolimod under real-world conditions, consistent with phase III trials. 176 V. Tichá et al. 2 Patients and Methods Key Points 2.1 Study Design and Patients Fingolimod is an approved oral therapy for patients with multiple sclerosis (MS). The GOLEMS study confirmed the efficacy of fingolimod in patients with MS under real-world settings. These data support the safety and tolerability of fingolimod in clinical practice. 1 Introduction In the EU, once-daily oral fingolimod 0.5 mg (FTY720; GilenyaÒ, Novartis Pharma AG) is approved for the management of adult patients with highly active forms of relapsing multiple sclerosis (MS), including those who fail to respond to first-line disease-modifying therapy (DMT) [1]. Fingolimod is a sphingosine-1-phosphate (S1P) receptor modulator that prevents the egress of auto-reactive lymphocytes from lymph nodes, thereby reducing their infiltration into the central nervous system (CNS) [2, 3]. Phase III trials have shown superior efficacy of fingolimod compared with intramuscular interferon (IFN)-b-1a (1-year TRANSFORMS study) and placebo (2-year FREEDOMS and FREEDOMS II studies) [4–6]. As of the second quarter of 2016, approximately 155,000 patients have been treated with fingolimod in both clinical trials and postmarketing settings, and the total patient exposure is approximately 343,000 patient-years [7]. Real-world studies complement the pivotal ‘randomized-controlled’ clinical trials conducted for approval process in providing evidence on the safety and efficacy of a drug under routine clinical practice [8]. The Gilenya (FingOLimod) in prescribing conditions defined by the CzEch regulator of drug reiMburSement (GOLEMS) study was planned to provide the requested healthcare outcomes data from MS patients receiving fingolimod under real-life conditions to the Health Authority and General Health Insurance Company of the Czech Republic. In this report, we present the results from the GOLEMS study, which investigated the effects of 12-month fingolimod treatment on the incidence and severity of relapses, disability progression and work capability in patients with MS. GOLEMS was a multicentre, observational, non-interventional, single-arm study designed to assess treatment outcomes in patients with MS receiving a minimum of 12 months of fingolimod therapy in the Czech Republic. All existing MS centres in the Czech Republic were asked to participate in the study. Fingolimod prescription was at the discretion of the treating physician and patient and was independent of participation in the study. Patients were included in accordance with the locally approved prescribing limitation by the Czech regulator for the reimbursement of drugs. Patients with MS who initiated fingolimod treatment at study entry or within 6 months before study entry as part of routine medical care were included in the study. All patients were assessed and monitored as per the revised label issued on 20 March 2012 and provided written informed consent form. Study visits were performed at baseline (treatment initiation), month 1, month 3 and every 3 months up to month 12, followed by every 6 months until the end of the 36-month study period. Women of child-bearing potential were informed about the potential risk of fingolimod use to the fetus, about the need for effective contraception and about the recommended 2-month wash-out period before a planned pr (...truncated)