New perspectives in the natural history of multiple sclerosis

Abstract

Multiple sclerosis (MS) has entered an era of immunomodulatory drug treatment, the impact of which on long-term disease progression remains controversial. The increasing use of these therapies has intensified our need to understand the true natural history of MS. The MS community is poised to establish whether the immunomodulatory drugs exhibit long-term benefits, with a suitable untreated natural history cohort likely the most practical and ethical comparator group. Thus, a thorough understanding of the natural history of MS is fundamental. In this review, we highlight recent advances in MS natural history over the last 5 years, with a focus on long-term population-based cohorts and factors associated with disease progression. Survival in MS has increased and longer times to irreversible disability have been reported in contemporary studies, indicating a slower accumulation of disability. Wide variation in the MS disease trajectory is evident within and between natural history studies, reflecting both methodologic considerations related to data collection and heterogeneity of disease activity. Recent publications have indicated that a younger age at disease onset is no longer indicative of a favorable outcome and further evidence supports the dissociation between relapses and long-term disability, although windows of opportunity may exist for some patients. We are now perhaps faced with our last chance to examine the true natural history of MS, so whether the reader is a practicing physician, health care provider, or researcher, or engaged in the pharmaceutical industry or in clinical trial design, recent advances in our understanding of the natural history of MS are of key significance.

Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation

“…RRMS is thought to last for around two decades before transition to SPMS. 70 Up to 15% of patients with RRMS may be retrospectively diagnosed with 'benign' MS. 17 There is significantly less consensus about the natural history of disability in the progressive phase of MS, with median times to EDSS 6 ranging from 15 to 32 years. 70 Very generally, progression to EDSS 4 is suspected to occur after one decade, EDSS 6 after 2 decades and EDSS 7 after three decades.…”

Practice patterns of US neurologists in patients with SPMS and PPMS

“…1 Approximately 80%-90% of patients with MS initially develop relapsing-remitting MS (RRMS). 2 Over approximately 10 years, an estimated 50% of untreated patients with RRMS will experience progressive neuronal damage, worsening of symptoms, a decline in both physical and cognitive abilities, and recategorization of their disease as secondary progressive MS (SPMS). 3 Approximately 15% of patients with MS experience primary progressive MS (PPMS), 2 which is characterized by few or no brain MS lesions and evidence of spinal atrophy in the absence of relapses.…”

“…2 Over approximately 10 years, an estimated 50% of untreated patients with RRMS will experience progressive neuronal damage, worsening of symptoms, a decline in both physical and cognitive abilities, and recategorization of their disease as secondary progressive MS (SPMS). 3 Approximately 15% of patients with MS experience primary progressive MS (PPMS), 2 which is characterized by few or no brain MS lesions and evidence of spinal atrophy in the absence of relapses. 4 Progressive MS disease courses are associated with a worse prognosis and decreased patient survival compared with other forms of MS. 5 There is currently no class I evidence for initiating treatment for patients with SPMS or PPMS.…”

Historical overview of the rationale for the pharmacological use of prolonged-release fampridine in multiple sclerosis

“…Any AE, n (%) 58 (81) 191 (84) 79 (66) 103 (86) Mild AEs, n (%) 16 (22) 59 (26) 36 (30) 39 (33) Moderate AEs, n (%) 35 (49) 98 (43) 36 (30) 53 (44) Severe AEs, n (%) 7 (10) 34 (15) 7 (6) 11 (9) Serious AEs, n (%) 0 (0) 16 (7) 3 (3) 5 (4) Possibly or probably treatment-related AEs, n (%)…”

“…With pharmacological treatment evolving, survival in MS has increased and longer times to irreversible disability have been reported in recent studies [9]. Wide variation in the progression of MS is evident both within and between natural history studies, driven by differences in assessment and data collection method ology together with the heterogeneous nature of the disease itself [10]. Reduced productivity and employment are suggested to be the greatest contributors to this burden, which are amplified by the early age of disease onset and long disease duration [11].…”