Genetics and Drug Response in MS: Why Some Patients Benefit More from First-Line Treatments
Multiple sclerosis (MS) is a complex autoimmune disease where the body mistakenly attacks the central nervous system. For patients and clinicians alike, the journey to manage this unpredictable disease often begins with one of two common first-line disease-modifying therapies (DMTs): glatiramer acetate (GA) or interferon beta (IFNβ). While both treatments can reduce relapses and delay disease progression, they don’t work equally well for everyone.
A 2011 study by Gross et al., published in the Journal of Neuroimmunology, dove deep into this variability. The researchers asked a fundamental question: Why do some MS patients respond better to certain therapies? Their focus: the role of genetics—specifically the HLA DRB1*1501 allele and other gene variants—in shaping treatment outcomes.
What Did the Study Find?
1. GA and IFNβ Perform Similarly—At First Glance
Gross and colleagues analyzed data from 756 patients with relapsing-remitting MS who had been treated with either GA or IFNβ. They found no significant difference in how long patients went without a disease "event" (relapse, MRI-detected lesions, or worsening disability) between the two treatments.
This supports results from earlier major clinical trials like BECOME and REGARD, which also showed GA and IFNβ were equally effective overall.
2. But Not All Patients Are Created Equal
Interestingly, the risk of relapse or disease activity decreased over time for patients on both medications. This suggests that some patients respond better than others, and these differences might emerge early in treatment.
To explore this, the team looked at patients who switched treatments. Some who didn’t respond to GA later did well on IFNβ, and vice versa. This “non-correlation” in responses indicates that the mechanisms behind each drug are distinct, and individual biology plays a key role.
The Genetics of Treatment Response
1. HLA DRB1*1501: A Clue for GA Responders
The HLA DRB1*1501 gene variant is well known in MS research for increasing disease risk. But could it also predict treatment response?
The study found that patients who were homozygous (had two copies) for this variant did better on GA, staying relapse-free longer than those with other genotypes. This effect wasn’t seen in IFNβ-treated patients, suggesting a GA-specific benefit.
This makes biological sense—GA is thought to interact with the immune system via MHC class II molecules, which are encoded by the HLA-DRB1 gene.
2. IRF8: A Possible Biomarker for IFNβ Response
Another gene, IRF8, caught the researchers’ attention. A variant called rs17445836A, linked to higher expression of interferon-response genes, was associated with shorter relapse-free survival in patients on IFNβ. This might mean these patients experience an exaggerated inflammatory response, undermining IFNβ’s effectiveness.
Interestingly, this IRF8 effect did not appear in GA-treated patients.
Implications for Personalized Medicine
The study highlights a growing truth in medicine: genetic differences matter. Understanding a patient's genetic makeup may one day help clinicians select the most effective treatment from the start—cutting down trial-and-error and improving long-term outcomes.
While the effects of these individual genetic markers (like HLA DRB1*1501 and IRF8) are modest, they open the door for future research and potential diagnostic tools.
The Road Ahead
This research shows the promise of pharmacogenetics—the study of how genes affect drug response—in MS care. Although we’re still far from routine genetic screening to guide MS treatment, this study helps lay the groundwork.
Future efforts may combine genetic profiles with other biomarkers (e.g., immune signatures or MRI data) to create truly personalized treatment plans.
For now, GA and IFNβ remain solid first-line options, but understanding who benefits most from each may redefine how we treat MS in the years to come.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Gross, R., Healy, B. C., Cepok, S., Chitnis, T., Khoury, S. J., Hemmer, B., ... & De Jager, P. L. (2011). Population structure and HLA DRB1* 1501 in the response of subjects with multiple sclerosis to first-line treatments. Journal of neuroimmunology, 233(1-2), 168-174.
