• This report is part of a 12-month Clinical Context series.

Gene transcription patterns separate multiple sclerosis (MS) patients into two groups, one of which appears more responsive than the other to standard therapies, researchers said.

In a study of 315 patients with relapsing-remitting MS and 48 with clinically isolated syndrome (a single demyelinating event), those with a transcription profile denoted as type B who were treated with glatiramer acetate (Copaxone) or interferon-beta drugs were significantly less likely to develop a major disease event than those with a type A profile, reported Philip De Jager, MD, PhD, of Brigham and Women's Hospital in Boston, and colleagues.

The hazard ratio for a disease event -- a demyelination event, new T2 hyperintense or gadolinium-enhancing lesion on MRI scans, or sustained 6-month disability progression -- was 0.6 for type B versus type A (95% CI 0.41 to 0.87, P=0.0077), the researchers reported online in Science Translational Medicine.

"This hazard ratio suggests that [patients with type B] MS are 40% less likely to have a relapse than [type A] MS," De Jager and colleagues wrote. "Stratifying MS subjects into meaningful subsets in this manner has potential for personalizing patient care and for enhancing our understanding of this disease."

They acknowledged, however, that their study had important limitations -- they did not evaluate responsiveness to other MS drugs such as fingolimod (Gilenya) or natalizumab (Tysabri), nor did they include patients with primary or secondary progressive MS.

On the other hand, not including the latter was also a strength of the study, in that De Jager and colleagues said that they deliberately chose not to attempt to find biomarkers associated with the conventional clinical MS classifications. Rather, they sought to identify differences among patients with a relatively uniform clinical presentation.

The goal, they wrote, was "to identify a priori subsets of subjects whose clinical course will differ over time."

To do so, they analyzed gene transcriptional activity in peripheral blood mononuclear cells using probes that detect mRNA for a large number of genes known to be involved in immune system pathways.

Among the patients providing peripheral blood mononuclear cell samples for the analysis were 141 who had not yet been treated for MS, 94 who had received glatiramer acetate for at least 3 months, and 128 who had been treated with interferon-beta drugs.

Treated patients had been followed for approximately 5 to 6 years, with major disease events recorded in their charts.

De Jager and colleagues used a statistical method called non-negative matrix factorization to identify different pattern types, which, they explained, does not assume that any particular genes are more important than others.

It showed that patients in the untreated group could be divided into two groups, with about 40% type A and the remainder as type B.

The researchers then classified the drug-treated patients into these disease types on the basis of their transcriptional profiles.

A Kaplan-Meier survival curve for events occurring in the treated patients, with both drug groups pooled, showed that event rates were similar in type A and B patients during the first year of treatment but then diverged.

By year 5, more than 80% of type A patients had experienced an event, compared with just over 60% of type B patients.

Another important limitation of the study was that transcriptional profiles were obtained only at baseline. Therefore, De Jager and colleagues noted, they had no information whether they changed over time with treatment, or even without treatment.

"We do not know whether an individual subject fluctuates between these two states or remains in a single state over time," they wrote.