Early Disease-Modifying Drug Therapy Delays Multiple Sclerosis Progression

A study compared historical and contemporary multiple sclerosis cases to determine how first-generation disease-modifying drugs affected disease progression.

First-generation disease-modifying drugs (DMDs) tended to delay the onset of severe neurologic disabilities seen in later multiple sclerosis (MS) stages, suggest the results of a study published in the May edition of Multiple Sclerosis Journal.

Study authors sought to determine differences in time to secondary disease progression, the MS stage marked by severe neurologic disabilities, by comparing an untreated historical cohort of participants to a contemporary participant cohort.

Although disease onset was relatively similar between the historic and contemporary cohorts, the research suggested more severe symptoms in the participants who did not have treatment available, and a greater therapeutic effect in those who began treatment early.

In particular, participants who received treatment with first-generation DMDs, typically interferon beta or glatiramer acetate, tended to reach secondary progression later than those who did not.

The research cohorts included 186 participants diagnosed between 1950 and 1964 in the historical group, which researchers found via the Gothenburg Incidence Cohort. The contemporary group included 730 participants diagnosed between 1995 and 2004, found via the Swedish National MS Registry. The contemporary cohort’s results were followed until 2008.

The authors noted that 76 patients in the contemporary group changed their treatment to natalizumab; however, the change occurred in the last 3 years of the study period. Participants whose disease began after 2000 tended to be treated earlier than those whose disease began during the mid 1990s, the authors noted. In addition, the amount of participants receiving DMD therapy increased during the study period.

After combining scores from several clinical areas and performing Kaplan-Meier estimate analysis, researchers determined no conspicuous difference in onset composition between the 2 groups, although they did note a higher proportion of patients in complete remission in the contemporary group, and a higher proportion of patients presenting with central nervous system symptoms in the historical cohort.

In both cohorts, an older age at symptom onset tended to mean a shorter time to reach secondary progression. In addition, those with more intense severity scores tended to reach secondary progression faster. When analyzing the data by gender, the authors also noted a longer time to reach secondary progression in women than in men.

In general, those in the untreated historical cohort tended to reach secondary progression faster than those in the cohort receiving treatment, even when data were stratified by gender or severity index score.

A Cox-regression analysis of the gender-divided data confirmed the findings of the first analysis, showing complete remission and monofocal onset to diminish hazard ratio. Older age at symptom onset resulted in a higher hazard ratio.

Although the analysis did not indicate a significant effect from treatment initiation time, both estimates showed a larger hazard ratio if treatment was delayed.

“We found there was a convincing ‘period effect,’ with a longer time to the onset of secondary progression in the contemporarily-treated than in the historical patient data,” the authors wrote. “. . . With a baseline of disease onset, we found no convincing evidence for a large imbalance between groups of à priori mild cases; therefore, part of the observed delay to the transition to secondary progression was probably due to the sustained effects of long-term treatment with first generation DMDs.”