Neurology · 2025
Effectiveness of Disease-Modifying Therapies in Patients With Late-Onset Relapsing-Remitting Multiple Sclerosis.
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Al-Araji Sarmad, Moccia Marcello, Jha Ashwani, Zhang Le, Eshaghi Arman, Kanber Baris, Bianchi Alessia, Yam Charmaine, Abdel-Mannan Omar, Goodkin Olivia, Pontillo Giuseppe, Hamed Weaam, Mohamud Suraya, Brownlee Wallace J, Chard Declan T, Chataway Jeremy, Chung Karen, De Angelis Floriana, Hammam Ahmed, Hacohen Yael, Khaleeli Zhaleh, Leary Siobhan M, Prados Ferran, Swanton Josephine, Thompson Alan J, Trip Sachid Anand, Wilson Heather, Wright Sarah, Nachev Parashkev, Barkhof Frederik, Toosy Ahmed T, Ciccarelli Olga
Аннотация
BACKGROUND AND OBJECTIVES: The benefit of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) is believed to decrease with age. We aimed to compare disease outcomes with DMTs between patients with late-onset RRMS (LO-RRMS) and adult-onset RRMS (AO-RRMS).
METHODS: This was a single-center, longitudinal, prospective analysis of patients who fulfilled the following criteria: (1) a diagnosis of RRMS and (2) initiation of a new DMT (dimethyl fumarate, fingolimod, glatiramer acetate, natalizumab, and ocrelizumab) within 3 months. Patients were followed up at years 1 and 2. We compared treatment outcomes (relapses, radiologic activity, disability progression, and no evidence of disease activity [NEDA]) between LO-RRMS (defined as age at onset of first symptom >45 years) and AO-RRMS (≥18 years and 45 years) using Poisson, logistic, and Cox regression models while adjusting for baseline variables. The analyses were repeated with an age cutoff of 50 years.
RESULTS: We studied 1,494 patients with AO-RRMS (mean age at onset: 29.6 years, 71% female) and 150 patients with LO-RRMS (50.2 years, 73% female) at treatment initiation. At DMT commencement, patients with LO-RRMS had shorter disease duration, higher Expanded Disability Status Scale (EDSS), more comorbidities, and were more likely to be treatment naive than patients with AO-RRMS. However, when adjusted, there were no differences in the probability of relapses (Coeff = -0.07; 95% CI -0.19 to 0.04, p = 0.24), EDSS progression (odds ratio [OR] 1.43, 95% CI 0.69-2.93, p = 0.33), MRI activity (OR 0.77; 95% CI 0.21-2.83, p = 0.70), and losing NEDA status (hazard ratio [HR] 0.93; 95% CI 0.73-1.18, p = 0.58) at year 1. Similar results were observed at year 2 in relapses (Coeff = -0.04; 95% CI -0.19 to 0.11, p = 0.60), EDSS progression (OR 1.33; 95% CI 0.69-2.93, p = 0.33), MRI activity (OR 1.30; 95% CI 0.38-4.38, p = 0.67), and loss of NEDA status (HR 0.99; 95% CI 0.77-1.26, p = 0.96). Similar results were observed using an age cutoff of 50 years. The percentages of patients who stopped DMTs because of side effects were similar between AO-RRMS and LO-RRMS.
DISCUSSION: Treatment outcomes over 2 years were similar between LO-RRMS and AO-RRMS. This indicates that care should be taken not to bias treatment decisions due to older age at onset of MS when patients demonstrate evidence of inflammatory activity. Limitations are the observational design, the single-center setting, and a relatively small LO-RRMS group.
CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with LO-RRMS have comparable outcomes with DMTs as patients with AO-RRMS over a 2-year period; this rating is because of baseline imbalances between treatment groups and a nonmasked outcome assessment.
METHODS: This was a single-center, longitudinal, prospective analysis of patients who fulfilled the following criteria: (1) a diagnosis of RRMS and (2) initiation of a new DMT (dimethyl fumarate, fingolimod, glatiramer acetate, natalizumab, and ocrelizumab) within 3 months. Patients were followed up at years 1 and 2. We compared treatment outcomes (relapses, radiologic activity, disability progression, and no evidence of disease activity [NEDA]) between LO-RRMS (defined as age at onset of first symptom >45 years) and AO-RRMS (≥18 years and 45 years) using Poisson, logistic, and Cox regression models while adjusting for baseline variables. The analyses were repeated with an age cutoff of 50 years.
RESULTS: We studied 1,494 patients with AO-RRMS (mean age at onset: 29.6 years, 71% female) and 150 patients with LO-RRMS (50.2 years, 73% female) at treatment initiation. At DMT commencement, patients with LO-RRMS had shorter disease duration, higher Expanded Disability Status Scale (EDSS), more comorbidities, and were more likely to be treatment naive than patients with AO-RRMS. However, when adjusted, there were no differences in the probability of relapses (Coeff = -0.07; 95% CI -0.19 to 0.04, p = 0.24), EDSS progression (odds ratio [OR] 1.43, 95% CI 0.69-2.93, p = 0.33), MRI activity (OR 0.77; 95% CI 0.21-2.83, p = 0.70), and losing NEDA status (hazard ratio [HR] 0.93; 95% CI 0.73-1.18, p = 0.58) at year 1. Similar results were observed at year 2 in relapses (Coeff = -0.04; 95% CI -0.19 to 0.11, p = 0.60), EDSS progression (OR 1.33; 95% CI 0.69-2.93, p = 0.33), MRI activity (OR 1.30; 95% CI 0.38-4.38, p = 0.67), and loss of NEDA status (HR 0.99; 95% CI 0.77-1.26, p = 0.96). Similar results were observed using an age cutoff of 50 years. The percentages of patients who stopped DMTs because of side effects were similar between AO-RRMS and LO-RRMS.
DISCUSSION: Treatment outcomes over 2 years were similar between LO-RRMS and AO-RRMS. This indicates that care should be taken not to bias treatment decisions due to older age at onset of MS when patients demonstrate evidence of inflammatory activity. Limitations are the observational design, the single-center setting, and a relatively small LO-RRMS group.
CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with LO-RRMS have comparable outcomes with DMTs as patients with AO-RRMS over a 2-year period; this rating is because of baseline imbalances between treatment groups and a nonmasked outcome assessment.