Conference Coverage

Initial high-efficacy MS therapy tied to less disability later


Starting treatment for relapsing-remitting multiple sclerosis (MS) with high-efficacy therapy (HET) is associated with lower long-term disability compared with a step-wise increase to reach more aggressive treatment later, new research suggests. However, there is a trade-off: In this study of nearly 300 patients, those treated with initial HET experienced more disease activity in the first 2 years than other participants.

The HET benefit emerged between 2 and 10 years into the study. For example, the mean Expanded Disability Status Scale (EDSS) scores were significantly lower at 6 years in the early, aggressive treatment group than in the later HET group (2.4 vs 3.3, respectively).

“Treatment decisions made around the time of diagnosis will affect long-term outcomes,” said lead author Anna He, MBBS, currently with the Department of Clinical Neuroscience, Karolinska Institute, Stockholm, and the UCL Queen Square Institute of Neurology in London.

Using the most efficacious disease-modifying therapies from the start minimizes disability, “whereas those patients escalating to high-efficacy disease-modifying therapies later do not seem to catch up to those who commenced earlier,” Dr. He said.

“Patients and clinicians should be aware of this when choosing treatment in early MS,” she added.

This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Patient-centered outcome

Instead of measures of brain volume, lesion count, serum neurofilament, or other biomarkers that are mainly of interest to clinicians and scientists, “the main outcome of interest to our patients is their disability,” Dr. He said. “The first question they ask at diagnosis is usually along the lines of: ‘What will my disability be in 10 years?’ ”

“This is what matters to patients and is fundamentally what motivated this study,” Dr. He added.

The investigators searched international MS registries for patients with relapsing-remitting MS starting HET, which included rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab.

They compared 117 participants who started HET within the first 2 years of clinical disease onset (the early group) with 181 participants who started HET after more than 4 years (the late group). All were followed for a median of 7.4 years (range, 6.4 to 8.6 years).

Difference in EDSS scores from baseline was the primary outcome. Both cohorts began the study with a mean EDSS score of 2.4, but between-group differences were significant at 10 years.

The secondary outcome of cumulative hazard of disability progression was higher in the early-treatment group from baseline to 2 years. Between the period of 2 and 10 years, the inverse was true.

In patients with highly active MS, “early exposure to high efficacy therapies is recommended,” Dr. He noted.

“We can already affect our patients’ lives enormously by utilizing our current toolbox in the most optimal way. It is our task to optimize this in a data-driven manner.”

Going forward, Dr. He plans to look at other outcomes, including patient-reported quality of life and health economic measures, and to take a different approach to future research.

Rather than assess MS outcomes from a disease-biology perspective, “I will be looking at MS outcomes from the perspective of its key stakeholders—the individual and society,” and the factors that influence them, Dr. He said.

Next Article: