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Published on: December 9, 2015
Age-related adverse events of disease-modifying treatments for multiple sclerosis: A meta-regression
Luca Prosperini1, Shalom Haggiag1, Carla Tortorella1
1Department of Neurosciences, San Camillo-Forlanini Hospital, Rome, Italy.
Objective:
To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action.
Methods:
We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms.
Results:
A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51, p < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52, p = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms (p = 0.017), especially above 45 years of age.
Discussion:
Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
Insights
Age increases risks for multiple sclerosis patients on depletive disease-modifying treatments (DMTs), particularly for neoplasms over age 45. Infections were not found to be age-dependent, possibly due to delayed onset.
Area of Science:
- Neurology
- Clinical Pharmacology
- Oncology
Background:
- Multiple sclerosis (MS) management involves disease-modifying treatments (DMTs) with diverse mechanisms of action.
- The safety profile of DMTs, particularly concerning age-related risks of infections and neoplasms, requires thorough investigation.
Purpose of the Study:
- To evaluate the hypothesis of an age-dependent increase in infections and neoplasms in multiple sclerosis patients receiving DMTs.
- To assess the influence of DMT mechanism of action (immunomodulatory, sequestrating, depletive) on these age-related risks.
Main Methods:
- A meta-regression analysis was performed on data from 45 randomized clinical trials (RCTs) of licensed DMTs.
- The study examined the incidence of overall infections, opportunistic infections, and neoplasms in relation to patient age and DMT type.
Main Results:
- Depletive DMTs were associated with a higher incidence of overall infections (event-rate ratio = 1.25, p < 0.001).
- Herpetic infections were more common with depletive and sequestrating DMTs.
- An interaction between age and depletive DMTs showed an increased incidence of neoplasms, particularly in patients over 45 years old (p = 0.017).
Conclusions:
- Age negatively impacts the safety of depletive DMTs, increasing neoplasm risk in patients over 45.
- No age-related increase in infections was detected, potentially due to delayed occurrence.
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