Dr Tjalf ZiemssenTjalf Ziemssen, MD
Interim results of the real-world PANGAEA 2.0 study have suggested that fingolimod (Gilenya, Novartis) is both safe and effective as a disease-modifying treatment (DMT) in patients with relapsing-remitting multiple sclerosis (MS) who switch from other therapies.1

Ultimately, patients treated with fingolimod experienced sustained effectiveness over a 2-year period, with a benefit being observed within 1 year of treatment. Of the more than 2000 patients in the trial, 24.9% switched from an oral DMT—dimethyl fumarate (n = 316) or teriflunomide (n = 180)—and 2.9% switched from daclizumab (n = 46). The average time of treatment prior to the switch was 1.5 years (dimethyl fumarate, 1.47 years; teriflunomide, 1.58 years; daclizumab, 9 months).

At the 24-month mark, the mean reduction in annualized relapse rate (ARR) was 73.5% (95% CI, 1.31 [±0.10] to 0.35 [±0.05]) in the oral DMT group, with those switching from dimethyl fumarate experiencing a reduction in ARR of 72.5% (95% CI, 1.31 [±0.12] to 0.36 [±0.06]).

The study group was led by Tjalf Ziemssen, MD, professor of Clinical Neuroscience, head, Multiple Sclerosis Center and Neuroimmunological Laboratory, and director, Division of Neurometabolism, University Clinic Carl-Gustav Carus. The data were presented at the 2019 American Academy of Neurology Annual Meeting, in Philadelphia, Pennsylvania. 

The investigators wrote that “fingolimod, the first oral DMT for the treatment of relapsing forms of MS, was approved in 2011. Since then, treatment options in MS have changed due to the approval of other oral DMTs or safety concerns of recently approved drugs.”

The sphingosine1-phosphate receptor modulator had been utilized by upward of 255,000 patients as of July 2018, with the total patient exposure exceeding 566,000 patient-years.

The study also evaluated patient-reported outcomes data in these patients, all of whom switched due to clinical or subclinical disease activity. Ziemssen and colleagues indicated that an updated analysis will be presented focusing on these measurements in the subgroups of the study, including stratification according to the number and frequency of pretreatments.

Previously, data presented at the European Committee for Treatment and Research in MS (ECTRIMS) 2017 Annual Meeting had shown that PANGAEA 2.0 patients (of which there were 1021 at the time) experienced a mean ARR reduction of 89.2% (95% CI, 1.3 [±0.06] to 0.14 [±0.02]). Expanded Disability Status Scale (EDSS) scores had remained stable at 2.4 (±0.37), and positive changes were observed in the clinical global impression scale at 6 months after switching to fingolimod.2

The results of PANGAEA 2.0 sustained those seen in its precursor study. In the original PANGAEA study, fingolimod was assessed over a 5-year observation period in more than 800 patients. The results showed stability, or a 6-month confirmed improvement, in year-over-year EDSS scores for approximately 90% of the patients.3

Additionally, in each year of treatment, between 68.6% (Year 1) and 81.0% (Year 4) of patients were relapses-free, and 43.6% of patients had neither relapse nor 6-month confirmed disability progression over 4 years of treatment.

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1. Ziemssen T, Ettle B, Schulze-Topphoff U. Effectiveness and Safety of Fingolimod in Patients Switching from Dimethyl Fumarate, Teriflunomide, and Daclizumab in Daily Clinical Routine: Interim Results from PANGAEA 2.0. Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA.
2. Ziemssen T, Kern R, Cornelissen C. First interim results of PANGAEA 2.0: Patients switching to fingolimod from other oral DMTs in daily clinical routine. Presented at: 2017 European Committee for Treatment and Research in MS Annual Meeting. October 27, 2017; Paris, France.
3. Ziemssen T, Lang M, Tackenberg B, et al. PANGAEA: Effectiveness and safety of fingolimod over 5 years in daily clinical practice. Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA.