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Published on: December 9, 2015
Association of Clinical Relapses With Disease Outcomes in Multiple Sclerosis Patients Older Than 50 Years
Steffen Pfeuffer1, Stephanie Wolff1, Derya Aslan1
1From the Department of Neurology (S.P., S.W., H.B.H.), University Hospital Giessen, Justus-Liebig-University Giessen; Department of Neurology (D.A., C.K., R.P.), University Hospital Essen, University Duisburg-Essen; Department of Neurology (L.R., M.K., M.P., S.G.M., T.R.), Medical Faculty, Heinrich Heine University Düsseldorf; Department of Neurology (P.A.), Medical Faculty, Heinrich Department of Neurology, Maria-Hilf-Clinic, Mönchengladbach; and Institute of Clinical Neuroimmunology (J.H.), LMU Hospital, Ludwig-Maximilians University Munich, Germany.
Background And Objectives:
Relapse and MRI activity usually decline with aging but are replaced by progression independent of relapse activity (PIRA) in patients with multiple sclerosis (PwMS). However, several older PwMS continue to experience clinical relapses, and the impact on their disease remains undetermined. We aimed to determine the impact of an index relapse on disease outcomes in patients older than 50 years and to identify risk factors of disadvantageous outcomes.
Methods:
We performed a secondary analysis from 3 prospective cohorts in Germany. We evaluated all PwMS 50 years and older with a relapse ≤60 days before a baseline visit and at least 18 months of follow-up compared with a control cohort of PwMS without a relapse. Patients were stratified according to age ("50-54" vs "55-59" vs "60+") or disease outcomes ("stable" vs "active" vs "progressive," according to the Lublin criteria). We analyzed relapses, MRI activity, relapse-associated worsening, and PIRA. Regression analysis was performed to evaluate the association of specific baseline risk factors and treatment regimen changes with disease outcomes at month 18.
Results:
A total of 681 patients were included in the "relapse cohort" (50+: 361; 55+: 220; 60+: 100). The "control cohort" comprised 232 patients (50+: 117; 55+: 71; 60+: 44). Baseline epidemiologic parameters were balanced among cohorts and subgroups. We observed increased abundance of inflammatory activity and relapse-independent disability progression in the "relapse" vs "control" cohort. In the "relapse" cohort, we identified 273 patients as "stable" (59.7%), 114 patients as "active" (24.9%), and 70 patients as "progressive" (15.3%) during follow-up. Cardiovascular risk factors (CVRFs) and older age at baseline were identified as risk factors of progressive, whereas disease-modifying treatment (DMT) administration at baseline favored stable disease. DMT during follow-up was associated with stable over active, but not over progressive disease.
Discussion:
A relapse-suggesting underlying active disease-in PwMS older than 50 years was associated with continued disease activity and increased risk of PIRA. Presence of CVRF and absence of DMT at baseline appeared as risk factors of disadvantageous disease courses. An escalation of DMT switch was associated with stable over active but not progressive disease.
Insights
In patients with multiple sclerosis over 50, a relapse indicates ongoing disease activity and higher risk of progression. Cardiovascular risk factors and lack of disease-modifying therapy increase this risk.
Area of Science:
- Neurology
- Immunology
- Clinical Research
Background:
- Aging typically reduces relapse and MRI activity in multiple sclerosis (MS).
- Progression independent of relapse activity (PIRA) becomes more prominent with age.
- Older MS patients experiencing relapses have undetermined disease impacts.
Purpose of the Study:
- Determine the impact of an index relapse on disease outcomes in MS patients over 50.
- Identify risk factors for unfavorable disease progression in this demographic.
Main Methods:
- Secondary analysis of 3 prospective German MS cohorts.
- Compared patients aged 50+ with a recent relapse to a control group without relapse.
- Stratified patients by age and disease outcomes (stable, active, progressive) over 18 months.
Main Results:
- Relapse cohort showed increased inflammatory activity and PIRA compared to controls.
- In the relapse cohort, 59.7% were stable, 24.9% active, and 15.3% progressive.
- Cardiovascular risk factors and older age predicted progressive disease; disease-modifying therapy (DMT) at baseline favored stable disease.
Conclusions:
- Relapses in older MS patients signal active disease and increased PIRA risk.
- Cardiovascular risk factors and no baseline DMT are risk factors for poor outcomes.
- Escalating DMT improved stable vs. active disease but not progressive disease.
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