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A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised,
Krzysztof Selmaj1, David K B Li, Hans-Peter Hartung
1Department of Neurology, Medical University of Lodz, Lodz, Poland. kselmaj@afazja.am.lodz.pl
The Lancet. Neurology
|June 15, 2013
Summary
Siponimod demonstrated a dose-response relationship in reducing brain MRI lesions in relapsing-remitting multiple sclerosis patients. Further investigation in a phase 3 trial is warranted due to its therapeutic effects and tolerability.
Area of Science:
- Neurology
- Pharmacology
- Immunology
Background:
- Siponimod is an oral selective sphingosine 1-phosphate receptor modulator (S1P1 and S1P5).
- It has a 7-day elimination half-life, facilitating washout.
- Relapsing-remitting multiple sclerosis (RRMS) is a chronic autoimmune disease affecting the central nervous system.
Purpose of the Study:
- To determine the dose-response relationship of siponimod on brain MRI lesion activity in RRMS patients.
- To characterize the safety and tolerability of siponimod in this population.
Main Methods:
- A double-blind, adaptive, dose-ranging, Phase 2 study was conducted across 73 European and North American centers.
- Adults (18-55 years) with RRMS were enrolled into two sequential cohorts.
- Patients received daily siponimod (0.25 mg to 10 mg) or placebo, with outcomes assessed over 3 or 6 months.
Main Results:
- A significant dose-response relationship was observed (p=0.0001) for siponimod's effect on reducing combined unique active MRI lesions.
- Reductions in lesions ranged from 35% to 82% compared to placebo across tested doses.
- Adverse events were reported in a higher percentage of patients on siponimod compared to placebo, with varying seriousness across dose groups.
Conclusions:
- Siponimod exhibits therapeutic effects on MRI lesion activity in RRMS.
- The drug's tolerability profile supports further investigation.
- A Phase 3 trial is recommended to confirm these findings.
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