Adults With Late-Onset MS at High Risk for Rapid Progression

More than one in 10 cases of multiple sclerosis (MS) begin after age 50, with more rapid progression to disability and less exposure to and benefit from disease-modifying therapies (DMTs), new data showed.

The study, which compared late-onset MS (LOMS) to adult-onset MS (AOMs) in a large Swedish registry, found that individuals diagnosed after age 50 had a greater degree of disability at diagnosis and were more likely to have primary progressive (PP) disease than those diagnosed earlier.

“This study distinguishes LOMS as a particularly vulnerable group and clinically supports close vigilance of these patients,” the authors noted.

The study was published online on February 23 in Neurology.

LOMS on the Rise

The onset of MS typically happens in young adulthood between ages 18 and 49, although a subset develops LOMS at age 50 and older. With people living longer, cases of LOMS are expected to rise, Elena Mouresan, MD, and colleagues from the Karolinska Institutet in Stockholm, Sweden, noted in their article.

Older patients have been largely excluded from clinical trials of DMTs, leading to uncertainty about the drugs’ efficacy and safety in this population. In addition, as people with MS age, they tend to develop progressive disease, which is refractory to treatment.

Using the Swedish MS registry, investigators compared clinical characteristics, DMT use, and disability progression in AOMS (onset between 18 and 49 years) and LOMS (onset at 50+ years).

Out of the entire 8739-patient cohort, 12% had LOMS. Compared with the AOM group, those with LOM were more disabled at diagnosis (median Expanded Disability Status Scale [EDSS] 2.5 vs 1.5; P < .001) and more likely to have PP MS (25% vs 5%).

The researchers evaluated use of modest-efficacy DMT (any interferon beta, glatiramer acetate, dimethyl fumarate, and teriflunomide) and high-efficacy DMT (rituximab, ocrelizumab, natalizumab, alemtuzumab, daclizumab, fingolimod, cladribine, and autologous hematopoietic stem cell transplantation).

Fewer individuals with LOMS were prescribed a DMT (75% vs 96%), investigators found. The frequency of high-efficacy DMT was also lower in LOMS than in AOMS (46% vs 74%). High-efficacy DMT was initiated in 51% of relapsing-remitting (RR)-LOMS vs 75% of RR-AOMS and in 33% of PP-LOMS vs 58% of PP-AOMS.

Rapid Progression

Compared with AOMS, individuals with LOMS had a greater risk of reaching EDSS milestones of 4 and 6 (adjusted hazard ratio [aHR], 2.71 and 2.67, respectively).

Individuals with RR-LOMS had an even higher risk of reaching EDSS 4 and 6 (aHR, 3.69 and 3.61, respectively) compared with individuals with RR-AOMS. However, for PPMS, the risk of reaching EDSS 4 and 6 was similar for LOMS and AOMS.

In an accompanying editorial, Dennis Bourdette, MD, and Lindsey Wooliscroft, MD, with the Department of Neurology, Oregon Health & Science University, Portland, Oregon, noted the importance of the finding that even though patients with relapsing LOMS have an increased risk of becoming disabled, they are treated less aggressively with DMT.

“The observation that relapsing LOMS leads to disability three times faster than relapsing AOMS places LOMS in a high-risk category for disability. These observations call for further investigation about the safety and efficacy of MS DMT in LOMS and investigations of why cases with LOMS are at higher risk of disability progression than AOMS,” they wrote.

“That said, assuming drug licensing agencies allow use of a given DMT in older patients and patients do not have contraindications, patients with LOMS should be prescribed a high-efficacy DMT based on their relapse and MRI activity and not barred from such treatment based on their age,” they added.

Funding for the study was provided by the Swedish Research Council, Swedish Brain Foundation, Region Stockholm Clinical Research Appointment, and the Lindholm Fredholms Foundation. Mouresan had no relevant disclosures. Bourdette has consulted for Magellan Health Services and Teladoc Health.