Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

Abstract

Objective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.

Risk of cardiovascular disease in patients with multiple sclerosis treated with fingolimod compared to natalizumab: A nationwide cohort study of 2095 patients in Denmark

“…Previous observational studies on fingolimod and cardiovascular safety with follow-up durations of 2–5 years conducted in different countries have with one exception 10 not included a comparison group and reported CVD events in 0.7%–8.5% of the included patients treated with fingolimod. 7 –13 This proportion of fingolimod-treated patients with CVD events during follow-up is lower than in our study where 169 of 1131 fingolimod-treated patients (14.9%) developed CVD and 141 of 1131 fingolimod-treated patients (12.5%) developed hypertension during up to 12 years of follow-up. Our results are in agreement with the LONGTERMS study, 24 a phase IIIb, open-label extension study conducted in 39 countries with up to 14 years of fingolimod exposure.…”

“…Several observational studies with follow-up durations of 2-5 years, have shown fingolimod to have an acceptable CVD safety. [7][8][9][10][11][12][13] These observational studies did, however, not include a comparator group, and CVD safety data were collected at visits in MS clinics throughout the study observation period by each patient's treating neurologist, typically in terms of seriousness, severity, duration, and link with the DMT. [7][8][9][10][11][12][13] The aim of this study was to examine CVD safety in fingolimod-treated patients including natalizumab as reference group since natalizumab and fingolimod have similar treatment indication in MS patients.…”

“…Several observational studies with follow-up durations of 2–5 years, have shown fingolimod to have an acceptable CVD safety. 7 –13 These observational studies did, however, not include a comparator group, and CVD safety data were collected at visits in MS clinics throughout the study observation period by each patient’s treating neurologist, typically in terms of seriousness, severity, duration, and link with the DMT. 7 –13…”

Cryptococcal chest wall mass and rib osteomyelitis associated with the use of fingolimod: A case report and literature review

“…A phase 3 clinical trial on fingolimod and a study after its introduction for clinical use showed that fingolimod causes lymphopenia in 8–13% of patients ( 34 , 35 ), mostly within the 1st year of use ( 36 ). This is not surprising because fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator, works by reducing the recirculation of C-C chemokine receptor type 7+ (CCR7 + ) lymphocytes ( 37 ) and this may have relevance for protection against cryptococcal infection.…”