Pharmacogenomics of Multiple Sclerosis: A Systematic Review

Area of Science:

• Pharmacogenomics
• Neuroimmunology
• Genetics

Background:

• Multiple sclerosis (MS) treatments show variable patient responses, potentially due to genetic factors.
• Numerous disease-modifying drugs for MS have been developed over the last two decades.
• Understanding genetic influences could lead to personalized MS therapy.

Purpose of the Study:

• To systematically review the existing literature on the pharmacogenomics of multiple sclerosis (MS) therapy.
• To identify genetic variations associated with patient response to MS disease-modifying treatments.
• To assess the current state of pharmacogenomic biomarkers for MS treatment selection.

Main Methods:

• Systematic literature search of PubMed/MEDLINE up to October 2018, adhering to PRISMA guidelines.
• Inclusion of studies investigating genetic variation and response to MS treatments (interferon-beta, glatiramer acetate, mitoxantrone, natalizumab).
• Data extraction included study design, genes, polymorphisms, outcomes, and statistical significance.

Main Results:

• 48 articles were reviewed, primarily candidate gene studies (87.5%).
• Pharmacogenomic evidence for MS drugs is often inconsistent across studies.
• Hypothesis-free approaches identified novel genes requiring validation; study design variations contribute to discordance.

Conclusions:

• Currently, no clinically actionable pharmacogenomic biomarkers exist for personalized MS treatment.
• Large-scale, uniformly designed studies are essential to validate and discover pharmacogenomic associations.
• Future research should explore rare variants and utilize next-generation sequencing for MS pharmacogenomics.