Can We Predict Who Benefits from Interferon Therapy in Multiple Sclerosis?

Multiple sclerosis (MS) is one of the most enigmatic autoimmune diseases of the central nervous system. While modern therapies have brought relief and slowed disease progression for many, not all patients benefit equally. One of the most widely used treatments, interferon-β (IFN-β), reduces relapses and brain inflammation in relapsing-remitting MS (RRMS). Yet, only about one in three patients experience strong benefits. Why the difference?

A study published in PLoS ONE by van Baarsen and colleagues (2008) tackled this question using a pharmacogenomics approach — the science of how an individual’s genetic and molecular profile influences their response to therapy. Their results revealed a fascinating clue: baseline gene expression patterns — particularly interferon response genes — may predict how well someone will respond to IFN-β therapy.

The Challenge: Why Do Patients Respond So Differently?
Doctors and researchers have long observed two broad categories of patients: “responders” and “non-responders” to IFN-β. The reasons behind this divide are complex. Neutralizing antibodies, which can block IFN-β’s action, explain some cases of non-response — but not all. This suggested that deeper, intrinsic differences at the cellular level might be shaping treatment outcomes.

The van Baarsen team hypothesized that patients’ immune systems were primed differently even before starting therapy, leading to varied drug responses.

The Study: Profiling the Immune System Before and After Therapy
The researchers followed two groups of Dutch RRMS patients:

Test group: 16 patients who provided blood samples before starting IFN-β, and again one, three, and six months after treatment.

Validation group: 30 additional patients for independent confirmation.

Using gene expression microarrays, they monitored thousands of genes to see how they changed after treatment.

The Findings: Baseline IFN Signature Shapes Response
Variation in drug response was striking.

Some patients showed robust activation of interferon-stimulated genes, while in others the same genes barely budged or even decreased.

Baseline mattered.

Patients who already had high expression of IFN response genes before therapy showed a much weaker response once given IFN-β. In contrast, those with low baseline expression exhibited strong gene activation after treatment.

Put simply: the more “switched on” your IFN pathway was before treatment, the less room there was for IFN-β to make a difference.

The pattern was consistent over time.

This negative correlation held steady at one, three, and six months into therapy.

Independent validation confirmed the results.

The second patient group reproduced the same relationship between baseline gene expression and response strength.

It’s intrinsic, not drug-specific.

In vitro experiments with patients’ immune cells showed similar differences, even outside the body. This means the variation is rooted in the cells themselves, not the injection schedule or drug brand.

What This Means for MS Treatment
These findings carry an important message: molecular profiling could help predict who will benefit most from IFN-β therapy. Instead of trial-and-error prescribing, doctors could one day test for a patient’s “baseline IFN signature” and decide whether IFN-β is worth starting — saving time, reducing side effects, and avoiding unnecessary costs.

The study also underscores the heterogeneity of MS. Two patients may share the same diagnosis, but their immune systems — and therefore their responses to therapy — may be fundamentally different. Precision medicine, tailored to molecular profiles, is likely the future for managing MS.

Looking Ahead
This research was an early step, and the authors were careful to note that larger, long-term studies are needed to link these molecular markers with real-world clinical outcomes like relapse rate or disability progression. Still, the principle is clear: genomics can guide treatment decisions in MS.

In the years since this study, pharmacogenomics has expanded dramatically, and we’re closer than ever to a time when baseline biomarkers will help doctors personalize therapy. For MS patients, this means a future where “will this drug work for me?” could be answered before the first injection.

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:
van Baarsen, L. G., Vosslamber, S., Tijssen, M., Baggen, J. M., van der Voort, L. F., Killestein, J., van der Pouw Kraan, T. C., Polman, C. H., & Verweij, C. L. (2008). Pharmacogenomics of interferon-beta therapy in multiple sclerosis: baseline IFN signature determines pharmacological differences between patients. PloS one, 3(4), e1927. https://doi.org/10.1371/journal.pone.0001927