Interplay between age and disease-modifying treatments in influencing infection risk in multiple sclerosis

Abstract

Background: Disease-modifying treatments (DMTs) can increase the risk of infections in multiple sclerosis (MS). Aged individuals are usually excluded from clinical trials, and there is uncertainty regarding safety of immunosuppressive DMTs in these patients. Objective: To investigate the association of DMTs, ageing and other clinical variables with risk of infections in MS patients. Methods: Prospective single-centre observational study collecting information on occurrence, type and grade of infections in patients followed at the MS centre, Lugano (Switzerland). Associations with infection risk were tested using multivariable Poisson and Cox regressions. Results: A total of 503 patients were included (injectables/untreated, n = 127; orals, n = 139; monoclonal antibodies (MAB), n = 237) and 326 infections recorded over 12.6 (11.6–14.0) months. As compared to injectable DMTs/no treatment, MAB and oral DMTs were positively associated with infection incidence (IRR = 2.32, 95% confidence interval (CI) = 1.39–3.89, p = 0.001; IRR = 2.04, 95% CI = 1.19–3.49, p = 0.009, respectively). After excluding COVID-19, the effect of MAB was stronger among patients <50 years (IRR = 5.90, 95% CI = 2.80–12.45, p < 0.001) than >50 years (IRR = 1.95, 95% CI = 0.91–4.15, p = 0.084). Higher disability and male sex were the only variables associated with severe infections. Conclusion: Treatment with MAB and oral DMTs is associated with higher incidence of infections, with a stronger effect in young MS patients. Disability appears the main predictor of severe infections regardless of treatment.

Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis

“…A 1-year observational study in MS ( N = 503) reported an increased risk of infections with orally administered DMTs (incidence rate ratio [IRR] 2.04 [95% CI 1.19–3.49]) and monoclonal antibody DMTs (IRR 2.32 [95% CI 1.39–3.89) vs. a control group who received interferons, glatiramer acetate or no DMT [ 1 ]. The effect of treatment with monoclonal antibody DMTs (vs. other treatments) on infections was stronger in younger (IRR 5.90) vs. older (IRR 1.95) subjects in this analysis.…”

“…Important demographic shifts are occurring in the population of people with relapsing multiple sclerosis (RMS). These include an increase in the overall age of this population, which is of potential importance as the efficacy of disease-modifying therapies (DMTs) has been reported to decrease, and the risk of infections has been reported to increase, as people with MS grow older [ 1 , 2 ]. It is therefore important to study the effects of individual DMTs in older and younger people with RMS separately.…”