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

Abstract

Background: Multiple sclerosis (MS) is a chronic disease that may require decades of ongoing treatment. Therefore, the long-term safety and efficacy of disease-modifying therapies is an important consideration. Methods: The LONGTERMS study evaluated the safety and efficacy of fingolimod in patients with relapsing MS (RMS) with up to 14 years of exposure. This phase IIIb, open-label extension study included patients aged ⩾ 18 years with confirmed RMS diagnosis who completed previous phase II/III/IIIb core/extension studies of fingolimod. Patients received fingolimod 0.5 mg orally once daily; safety and efficacy (clinical and magnetic resonance imaging) were the main outcomes. Results: Of 4086 patients from the core studies who entered LONGTERMS, 3480 (85.2%) completed the study. The median age (range) was 38 (17–65) years and median fingolimod exposure was 944.5 (range 75–4777) days. Overall, 85.5% of patients experienced at least one adverse event (AE); most common AEs (⩾10%) were viral upper respiratory tract infection (17.3%), headache (13.3%), hypertension (11.0%) and lymphopenia (10.7%). Among patients with serious AEs (12.6%), basal cell carcinoma and MS relapse (0.9% each) were most frequently reported. The aggregate annualized relapse rate decreased from 0.22 (in years 0–2) to 0.17 (years 0–10); 45.5% of patients remained relapse free after 10 years. At year 10, 63.2% of patients were free from 6-month confirmed disability worsening. Conclusion: This long-term observational study of patients treated for up to 14 years with fingolimod confirmed its established safety profile with no new safety concerns. Patients with RMS receiving fingolimod had sustained low levels of disease activity and progression. Trial Registration: ClinicalTrials.gov identifier: NCT01201356.

Long-term prognostic value of longitudinal measurements of blood neurofilament levels

“…The present post hoc biomarker analysis included pooled data from patients with RRMS who were randomly assigned to receive fingolimod 0.5 mg once daily during the core period of the 24-month FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) (NCT00289978) 14 or 12-month Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing -Remitting Multiple Sclerosis (TRANSFORMS) (NCT00340834) 15 phase 3 trials (both trials had essentially the same inclusion/exclusion criteria), continued on the same treatment and dose in the respective extension studies (NCT00662649 and NCT00340834), 16 , 17 and thereafter transitioned into the open-label long-term extension LONGTERMS study for up to 10 years (NCT01201356). 18 Details of the individual study design and patient population are reported elsewhere. 14 – 18 NfL analysis was performed in all samples where informed consent was granted, irrespective of clinical outcomes.…”

“…18 Details of the individual study design and patient population are reported elsewhere. [14][15][16][17][18] NfL analysis was performed in all samples where informed consent was granted, irrespective of clinical outcomes.…”

S1P/S1P Receptor Signaling in Neuromuscolar Disorders

“…Fingolimod (FTY720) is an immunosuppressant which prevents lymphocyte egress from the lymph nodes, thereby, reducing autoaggressive lymphocyte migration into the central nervous system. Fingolimod (FTY720) is currently used in the treatment of relapsing multiple sclerosis [121]. In addition, it is safe and well-tolerated and can reduce circulating lymphocytes in patients suffering from amyotrophic lateral sclerosis [122].…”

“…In addition, Bondì et al [128] observed that S1P/S1PR3 axis plays a negative role in muscle mass maintenance and force in soleus during aging and extracellular S1P exerts a protective effect during muscle fatigue development [129]. S1P/S1PR3 signaling also modulates excitation-contraction coupling and intracellular calcium mobilization [121][122][123][124][125][126][127][128][129][130].…”

Current requirements for studies of drugs for the pathogenetic treatment of multiple sclerosis

“…При более активном течении РС и недостаточной эффективности этих препаратов используются более сильные ЛС, однако они имеют и более широкий спектр побочных эффектов. Опыт применения этих препаратов также достаточно большой -более 10 лет [7].…”