Younger age at multiple sclerosis onset is associated with worse outcomes at age 50.

Objective: Older age at multiple sclerosis (MS) onset has been associated with worse 10-year outcomes. However, disease duration often exceeds 10 years and age-related comorbidities may also contribute to disability. We investigated patients with>10 years disease duration to determine how age at MS onset is associated with clinical, MRI and occupational outcomes at age 50.
Methods: We included patients enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital with disease duration>10 years. Outcomes at age 50 included the Expanded Disability Status Scale (EDSS), development of secondary-progressive multiple sclerosis (SPMS), brain T2-lesion volume (T2LV) and brain parenchymal fraction (BPF), and occupational status. We assessed how onset age was independently associated with each outcome when adjusting for the date of visit closest to age 50, sex, time to first treatment, number of treatments by age 50 and exposure to high-efficacy treatments by age 50.
Results: We included 661 patients with median onset at 31.4 years. The outcomes at age 50 were worse the younger first symptoms developed: for every 5 years earlier, the EDSS was 0.22 points worse (95% CI: 0.04 to 0.40; p=0.015), odds of SPMS 1.33 times higher (95% CI: 1.08 to 1.64; p=0.008), T2LV 1.86 mL higher (95% CI: 1.02 to 2.70; p<0.001), BPF 0.97% worse (95% CI: 0.52 to 1.42; p<0.001) and odds of unemployment from MS 1.24 times higher (95% CI: 1.01 to 1.53; p=0.037).
Conclusions: All outcomes at age 50 were worse in patients with younger age at onset. Decisions to provide high-efficacy treatments should consider younger age at onset, equating to a longer expected disease duration, as a poor prognostic factor.
Competing Interests: Competing interests: GB has received an endMS PostDoctoral Fellowship award from the Multiple Sclerosis Society of Canada. BCH has received research support from Analysis Group, Celgene (Bristol-Myers Squibb), Verily Life Sciences, Merck-Serono, Novartis and Genzyme. CB has received a PostDoctoral Fellowship award from the Swiss National Science Foundation. BG has received grant support from Merck Serono and Verily Life Sciences. HAL has received research support from Verily Life Sciences, Octave Bioscience and the Department of Defense. MP-T reports no disclosures. CRGG has received research funding from Sanofi, the National Multiple Sclerosis Society, the International Progressive Multiple Sclerosis Alliance, the National Institutes of Health, the US Office for Naval Research, the Bright Focus Foundation, as well as travel support from Roche Pharmaceuticals; CRGG owns stock in Roche, Novartis, GSK, Alnylam, Protalix Biotherapeutics, Arrowhead Pharmaceuticals, Cocrystal Pharma, Sangamo Therapeutics, Alcon. RB has received consulting fees from Bristol-Myers Squibb and EMD Serono and research support from Bristol-Myers Squibb, EMD Serono, Novartis, the US Department of Defense, the National Institutes of Health and the National Multiple Sclerosis Society. HW has consulted for Genentech; Tiziana Life Sciences; IM Therapeutics; MedDay Pharmaceuticals; vTv Therapeutics; IMAB Biopharma and received research support National Institutes of Health; National Multiple Sclerosis Society; Sanofi Genzyme; and Genentech. TC has received compensation for consulting from Banner Life Sciences, Biogen, Bristol Myers Squibb, Novartis Pharmaceuticals, Roche Genentech and Sanofi Genzyme. She has received research support from the National Institutes of Health, National MS Society, US Department of Defense, Sumaira Foundation, Brainstorm Cell Therapeutics, Bristol-Myers Squibb, EMD Serono, I-Mab Biopharma, Mallinckrodt ARD, Novartis Pharmaceuticals, Octave Bioscience, Roche Genentech, Sanofi Genzyme and Tiziana Life Sciences.
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