#ECTRIMS2019 – Age Seen as Crucial in MS Outcomes, with 40 Marking Shift from Relapses to Progression

Age at disease onset is tightly linked to clinical outcomes in multiple sclerosis patients, a Swiss study in those on disease-modifying therapies (DMTs) reports. It found a risk of continuous relapses more likely in pediatric MS, and that of disease progression in those with adult-onset MS.

Patients at age 40 seem to arrive at a “critical” juncture between relapses and progression, its researchers added, recommending that age be considered when designing clinical trials or choosing among DMTs.

The research, “Age at disease onset and clinical outcomes in patients with multiple sclerosis on immunomodulatory treatment,” was presented by Viktor von Wyl, a PhD with the University of Zurich, at the 35^th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) that ran in Stockholm on Sept. 11–13.

Pediatric-onset MS patients are known to have higher relapse rates and initially slower disability progression that those with adult-onset disease. But data on how age differences impact clinical outcomes throughout the life of patients on DMTs is still scarce.

A team from Switzerland used a Swiss health insurers database to investigate such outcomes. The database has information on 14,718 MS patients (mean age of 39) who started on a DMT between 1995 and 2017; its MS-related data is provided annually by board-certified neurologists.

As of the analysis date, patients had a mean disease duration of six years, more than two-thirds (69%) were women, and 85% had relapsing-remitting MS (RRMS).

A total of 5,817 patients were eligible for study inclusion. They were on a DMT for a minimum of one year up, had at least two years of follow-up without gaps in treatment history, and had been diagnosed on or after Jan. 1, 1993.

A statistical method was used to evaluate the effect of age at disease onset on future relapses and disability progression, assessed through a person’s Expanded Disability Status Scale (EDSS) score.

Regarding DMT use, 71.8% of the patients were treated with interferon-beta — brand names are Avonex, Rebif, Betaseron, Extavia, Plegridy — and 11.2% were using glatiramer acetate (marketed as Copaxone, or its generic Glatopa). The remaining patients received so-called higher efficacy DMTs, like Gilenya (fingolimod; 10.7% of the patients), Tysabri (natalizumab; 4.6%), Tecfidera (dimethyl fumatare; 1.1%), and Aubagio (teriflunomide; 0.6%).

Median follow-up for these patients was 6.5 years.

Results showed that the risk of confirmed disability progression (based on EDSS scores) after starting DMT treatment was stable in patients with disease onset from early childhood through to about age 32, when this risk began to increase (up to age 37). Disability progression then markedly accelerates around age 38, von Wyl said. Progression began to stabilize again at around 45 years old, but it was stability with a relatively high EDSS score.

In contrast, the link between age at disease onset and relapses was nearly linear. Relapse risk was highest at younger ages and fell continuously from childhood to around 35 years old. As an example, a person with first MS symptoms at age 20 was 1.5 times more likely to have a relapse while on a DMT than a 38-year-old with onset, the study reported. Factors such as gender, relapse history prior to DMT initiation, EDSS, and disease severity had been accounted for by researchers.

Findings on relapses and age — and on progression and age — are in line with previous studies, von Wyl said.

“Does the confirmed disability progression risk curve [seen in older patients] differ by DMT type?” von Wyl then asked.

He was cautious about data here, noting that these data are not “entirely conclusive, but at this time there is NO statistical evidence.” From a clinical point-of-view, von Wyl believes that the main question is: “Can we shift the high-risk phase towards later ages with higher efficacy drugs?” More studies are needed to address this question, he said.

Based on the results, von Wyl concluded that “age at DMT start is an important factor affecting relapse and confirmed disability progression independently of other disease characteristics,” and possibly type of DMT.

He also noted that “patients older than 40 years starting DMT have a higher risk for disability progression.” He stressed this is not to suggest that “DMTs are ineffective.” Rather, “it’s just that the risk for the first disability event drastically increases” with age.

Von Wyl also emphasized that “the age between 37 and 40 years seems critical with regard to the compensation of the central nervous system damage caused by MS,” meaning the system’s ability to compensate for such damage. Future studies, he said, should focus on this particular age group, instead of looking at adult vs. pediatric MS onset.

Likewise, he believes these data “should be considered when designing clinical trials.”