Given those findings, age should be considered in the risk/benefit assessment that’s used in the decision-making process for choosing MS treatments, the researchers suggested.
The study, “The Age-Related Efficacy of Dimethyl Fumarate and Natalizumab in the Real-World Management of Multiple Sclerosis,” was published in the journal Pharmaceuticals.
A patient’s age has a key role in modeling the immune system and therefore may affect both MS progression and an individual’s response to treatment. However, most clinical trials undervalue age as a major contributor to disability in MS patients, researchers say.
Now, a team of researchers in Italy has investigated age-related influence on disability among people with MS in a real-world setting. These patients were treated with two approved disease-modifying therapies, or DMTs, specifically Tecfidera and Tysabri, both marketed by Biogen.
The influence of age at disease onset also was assessed, along with the effect of disease duration on disability. Disability was evaluated using the expanded disability status scale (EDSS), in which a higher score indicates greater disability.
The study lasted 36 months (three years) and compared two groups of patients. One comprised 173 people with mild to moderate MS who were treated with Tecfidera, while the other had 94 patients with high disease activity who were given Tysabri. Both groups were similar in average ages, ages at disease onset, and disease duration.
The results showed that patients treated with Tysabri had significantly higher EDSS scores — an average of 3.5 — compared with those treated with Tecfidera, whose scores averaged 2.5.
According to the researchers, these results may be explained by two factors: patients in the Tysabri group had a higher disease activity, and Tysabri was used as a second-line therapy. Second-line means that a treatment is given after the initial therapy fails to work or is found to be inadequate.
“This difference is consistent with the so-called second-line DMTs, reserved for patients suffering from a high-activity disease type,” the researchers wrote.
The data also showed that age, age at onset, and disease duration all were strongly correlated with EDSS in both groups, meaning that higher values in these three parameters were associated with greater disability.
Of note, Tysabri-treated patients showed a greater ability to maintain lower EDSS scores (1.0 to 3.0) over time versus higher scores (3.5 to 7.0), compared with Tecfidera-treated patients, the researchers found. These results suggest that Tysabri was better than Tecfidera in preventing disability progression at the initial disease stages.
“These observations agree in suggesting a neuroprotective effect of [Tecfidera], which is more evident in the late stage of disease when degenerative damage occurs; this is unlike [Tysabri], which demonstrates its main efficacy in the early stage, when the neuroinflammation is prominent,” the team wrote.
High EDSS scores, those of 3.5 or greater, were typically reached at the age of 39-40 (mean of 39.3 years), regardless of treatment type, the researchers also found. This suggested that there is “an age-dependent threshold effect” for reaching scores higher than 3.5.
“Specifically, 39.3 years of age represents a cut-off value beyond which patients’ disabilities are prone to evolve, regardless of the DMT” used, the researchers wrote.
These results imply that “differences in neurological disability between the first- [Tecfidera] and second-line [Tysabri] DMTs are detectable only before a determined age threshold but not after,” they added.
Overall, based on the findings, the team concluded that DMTs prescribed for MS “must be [given] as early as possible to achieve the maximum effectiveness from first-line or second-line treatment.”
Additionally, age should be considered “in the evaluation of risk/benefit for decision making concerning DMT in MS,” given that it is “a major contributor in disability and response to therapy in current management” of the disease.
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