Treatment trials in progressive MS--current challenges and future directions

Area of Science:

• Neurology
• Clinical Trials
• Neuroimmunology

Background:

• Immunomodulatory treatments have revolutionized relapsing-remitting multiple sclerosis (RRMS) care.
• Progressive forms of multiple sclerosis (MS), including primary progressive MS (PPMS) and secondary progressive MS (SPMS), lack effective treatments.
• Patients with progressive MS experience continuous functional decline without consistent therapeutic benefit.

Purpose of the Study:

• To review current clinical trial designs for progressive MS.
• To identify and discuss key challenges in conducting clinical trials for progressive MS.
• To propose strategies for overcoming these hurdles in trial design and execution.

Main Methods:

• Review of existing literature and clinical trial methodologies in progressive MS.
• Analysis of challenges related to outcome measures, natural history, and imaging in progressive MS trials.
• Discussion of implications for trial duration and patient selection.

Main Results:

• Current clinical trial designs for progressive MS face significant challenges.
• Reliable measurement of clinical progression, understanding of natural history, and role of imaging outcomes impede optimal trial design.
• The use of time to a predefined change on the Expanded Disability Status Scale (EDSS) has led to long trials and limited patient inclusion.

Conclusions:

• Effective clinical trial designs are crucial for developing treatments for progressive MS.
• Addressing challenges in outcome measurement and trial conduct is essential.
• Innovative strategies are needed to improve the efficiency and inclusivity of progressive MS clinical trials.