The natural history of early versus late disability accumulation in primary progressive MS

Koch, Marcus; Greenfield, Jamie; Javizian, O.; Deighton, Stephanie; Wall, Winona; Metz, Luanne M.

doi:10.1136/jnnp-2014-307948

Cited by 21 publications

(22 citation statements)

References 19 publications

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“…Overall, we found disease course rather than age at onset to be the main predictor of disability in MS, as others have found [4,6,7,10,11,17,33]. The pre-eminence of initial disease course over age at onset in predicting disability progression might be explained by pathogenic links between primary progression, axonal damage and irreversible disability.…”

Section: Discussionsupporting

confidence: 52%

“…By contrast, a progressive course from disease onset worsens the rapidity of disability progression, whatever the age at MS onset. Late onset was previously found to be a strong predictor of conversion from RR onset to secondary progressive MS [2,4,7,11]. Rapidity of disability progression associated with LOMS may not be due to the greater frequency of PP disease among this group.…”

Section: Discussionmentioning

confidence: 98%

“…Only a few studies specifically assessed MS prognosis associated with LOMS [8,9,10,11,16,17,25,26,27,28] accounting for confounding factors such as disease course with a rigorous statistical approach. The LORSEP cohort is population-based, avoiding referral bias.…”

Section: Discussionmentioning

confidence: 99%

“…Although LOMS is considered to be associated with adverse prognosis [2,3,4,5], whether it has any prognostic relevance independent of primary progressive MS (PPMS), an established marker of poor prognosis strongly associated with older age at onset, remains a debatable issue [6,7,8,9]. Age at disease onset was an independent predictor of early progression to disability only in relapsing-remitting onset MS (RRMS) but not in PPMS in a cohort of 2,054 patients [10], while older age was independently associated with short time to disability in a cohort of 500 PPMS patients [11]. …”

Section: Introductionmentioning

confidence: 99%

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Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

Guillemin

Baumann²,

Epstein³

et al. 2017

Neuroepidemiology

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Background: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. Methods: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling. Results: Among 3,597 patients, 245 had LOMS. Relapsing-remitting (RR) disease was less frequent with LOMS than AOMS (51.8 vs. 90.8%, p < 0.0001). PP course, LOMS and male gender predicted short time to EDSS 4 and 6. Worse outcome with LOMS (time to EDSS 4 and 6, HR 2.0 [95% CI 1.7-2.4] and 2.3 [1.9-2.9]) was independent of PP course or male gender. LOMS had greater impact on RR than PP disease (time to EDSS 4 and 6, HR 3.1 [2.3-4.0] and 4.0 [2.9-5.6]). Only LOMS predicted time from EDSS 4 to 6 (p < 0.0001). Conclusions: Late onset MS was strongly associated with poor prognosis, independent of initial disease course, in predicting the disability progression along time.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

Guillemin

Baumann²,

Epstein³

et al. 2017

Neuroepidemiology

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“…Disability is typically accrued more rapidly in PPMS as compared to SPMS, but it should be noted that relapses may still occur in subjects with SPMS, occasionally even in subjects with PPMS. 12 …”

Section: Clinical Features and Coursementioning

confidence: 99%

Progressive multiple sclerosis

Ontaneda

Fox

2015

Current Opinion in Neurology

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Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease.

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Diagnosing primary progressive multiple sclerosis

Newsome¹

2016

Case Studies in Multiple Sclerosis

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The natural history of early versus late disability accumulation in primary progressive MS

Cited by 21 publications

References 19 publications

Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

Progressive multiple sclerosis

Diagnosing primary progressive multiple sclerosis

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