Primary progressive multiple sclerosis: current therapeutic strategies and future perspectives

Area of Science:

• Neuroimmunology
• Clinical Neurology
• Pharmacology

Background:

• Multiple sclerosis (MS) is a chronic, heterogeneous central nervous system inflammatory disease.
• Primary progressive multiple sclerosis (PP MS) is a rare subtype with continuous worsening disability.
• Current disease-modifying therapies lack approval for PP MS due to trial inconsistencies.

Purpose of the Study:

• To review randomized trials of disease-modifying treatments for PP MS.
• To discuss the efficacy of various interventions, including immunosuppressants, immunomodulators, and monoclonal antibodies.
• To highlight emerging therapeutic strategies and future trial considerations.

Main Methods:

• Systematic review of randomized clinical trials for PP MS treatments.
• Analysis of trial results for immunosuppressants, immunomodulators, monoclonal antibodies, and neuroprotective agents.
• Evaluation of the ocrelizumab trial and its implications.

Main Results:

• The ocrelizumab trial is the first to meet a primary disability endpoint in PP MS.
• B cell targeting demonstrates potential for preventing disease progression.
• Ongoing trials investigate cell metabolism modulation and inflammatory pathway inhibition.

Conclusions:

• B cells represent a promising therapeutic target for PP MS.
• Future PP MS trials should incorporate broader efficacy endpoints beyond physical disability.
• Cognition, quality of life, advanced MRI, and biomarkers are crucial for future assessments.