Current age, disease duration impact MS-related mortality

Current age exerted a greater impact on MS-related mortality than disease duration among patients with relapsing-onset MS, with a less clear impact among patients with primary progressive MS, according to findings published in Neurology.

The results in patients with relapsing MS highlighted “the major prognostic role of age” in MS, according to the researchers, and indicated “an amnesic process” in MS that aligned with previous research in disability progression.

“Two statistical frameworks can be used to study mortality compared with the general population. The most commonly used is a multiplicative approach, either through standardized mortality ratios (SMR) or multivariate models,” Fabien Rollot, MSc, and colleagues wrote. “A second framework, widely used in cancer studies but rarely in MS, is the use of an additive model which assumes that the mortality rate is the sum of the expected death rate and an excess death rate (EDR) due to the disease. Describing the dynamics of EDR and the impact of covariates on this dynamic is an important task which provides essential epidemiological and clinical information.”

However, such an analysis has never been performed in MS, according to Rollot — who is affiliated with the University of Lyon, Claude Bernard Lyon 1, and the Center for Research in Neuroscience in Lyon, among other institutions, all of which are in France — and colleagues. As a result, the researchers aimed to examine, in France, the dynamics of the EDR according to disease duration or current age and to analyze the impact of age at MS onset on these dynamics in each initial MS phenotype. Additionally, they evaluated the impact of sex on the EDR.

Rollot and colleagues examined data from 18 MS expert centers in France. Participants included patients with MS in metropolitan France whose clinical onset of MS occurred between 1960 and 2014. The researchers updated vital status on Jan. 1, 2016, and modeled the logarithm of EDRs through a “multidimensional penalized spine” of age and disease duration, according to the study results.

The study included 37,524 participants (71% women; mean age at MS onset, 33 years). During the study period, 2,883 deaths (7.7%) occurred, including 2,142 deaths among patients with relapsing-onset MS (6.5%) and 741 among patients with PPMS (16.4%), and 7.8% of patients were lost to follow-up.

Among patients with relapsing-onset MS, the researchers observed no excess mortality in the first 10 years after disease onset. Thereafter, EDRs increased with current age, whatever the age at MS onset was, according to the results from Rollot and colleagues. Additionally, the researchers reported a convergence of EDR values among participants with a current age of 70 years in which the EDRs were identical whatever the age was at disease onset. This indicated that “disease duration had no more impact,” according to the researchers. Rollot and colleagues found that EDRs were increased among men (excess HR = 1.46; 95% CI, 1.25-1.7).

“It is of note that the confidence intervals become wider with increasing age, which should lead to caution in interpreting the results for extreme ages,” the researchers wrote. “Even if these rates were the same, the cumulative effects of the EDR, given by net probabilities of being alive at current age 70, remained quite different according to the age at MS onset. They increased with age at onset, from 79% (95% CI, 76% to 81%) in patients aged 30 years at onset to 93% (95% CI, 91% to 95%) for patients aged 50 years at onset.”

Conversely, the researchers found that EDRs “rapidly increased” from the time of disease onset among patients with PPMS, according to the study results. Among these patients, the researchers observed a relationship between EDRs and age at onset, but not sex.

“In PPMS, excess mortality rapidly increased from disease onset and depended on age at MS onset whatever the current age. For patients aged 20 years at onset, which corresponds to a limited number in the study population, the results should be interpreted with caution beyond 30 years of disease duration due to the lack of precision of the estimates,” Rollot and colleagues wrote. “The net survival probabilities were higher for patients with shorter disease duration. Net probabilities of being alive at current age 70 varied from 51% (95% CI, 45% to 58%) for patients aged 30 at MS onset to 86% (95% CI, 83% to 89%) for patients aged 50 at MS onset.”

According to the researchers, no prior study has — to their knowledge — examined the dynamics of EDR in such an extensive way, making comparisons between these results and other studies difficult. However, the observed and expected survival in the study population confirmed that survival in patients with MS is different from the matched general population, which aligns with previous research.

“The scope of our study was the application of the excess rate models in an additive framework, but in future studies, it would be interesting to compare this approach to the multiplicative framework, typically by calculating SMR, often used in MS,” Rollot and colleagues wrote.