Natural history of secondary-progressive multiple sclerosis

Tremlett, Helen; Zhao, Yinshan; Devonshire, Virginia

doi:10.1177/1352458507084264

Cited by 198 publications

(169 citation statements)

References 38 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…[16][17][18][19][20][21] For the current study, 8 of the 2,485 eligible were excluded because of unclear relapse histories, leaving 2,477 patients (table). The follow-up time from MS onset totaled 51,120 person-years with 11,722 postonset relapses.…”

Section: Resultsmentioning

confidence: 99%

“…[15][16][17][18][19][20][21] Briefly, patients were selected from the populationbased British Columbia MS (BCMS) database covering all 4 MS clinics in this Canadian province. Inclusion criteria (previously depicted as a flow chart 21 ) were laboratory-supported or clinically definite MS (Poser criteria 22 ); relapsing onset with first symptoms before July 1988 (to maximize the possibility of a meaningful follow-up time [no minimum follow-up time was required; those with a rapid disease course were eligible]); Ն1 EDSS score; and registered with a BCMS clinic before July/1998 (to enable establishment of the disease course).…”

Section: Methods Patientsmentioning

confidence: 99%

“…The main outcomes were time to sustained EDSS 6 (requires a cane), confirmed Ͼ150 days later, with all subsequent scores being Ն EDSS 6 and time to secondary progression (SP). 19,23 A relapse was defined as worsening neurologic symptoms Ͼ24 hours, without fever or infection. Once an immunomodulatory drug (IMD, first licensed in 1995) was initiated, subsequent relapses and EDSS scores were excluded.…”

Section: Methods Patientsmentioning

confidence: 99%

“…18 Using a similar approach, a time to EDSS 6 was imputed based on 2 clinically plausible scenarios: 1) optimistic assumed EDSS 6 was reached at the first clinic visit; 2) midway assumed EDSS 6 was reached halfway between onset and the first clinic visit. Few patients had an unknown time to SPMS (n ϭ 30), 19 such that a sensitivity analysis was not warranted. SPSS (version 15) was used for statistical analyses.…”

Section: Methods Patientsmentioning

confidence: 99%

See 3 more Smart Citations

Impact of multiple sclerosis relapses on progression diminishes with time

Tremlett¹,

Yousefi²,

Devonshire³

et al. 2009

Neurology

207

172

View full text Add to dashboard Cite

Objective:The relationship between relapses and long-term disability in multiple sclerosis (MS) remains to be fully elucidated. Current literature is conflicting and focused on early relapses. We investigated the effects of relapses at different stages on disability progression. Methods:We conducted a retrospective review of 2,477 patients with definite relapsing-onset MS followed until July 2003 in British Columbia, Canada. Time-dependent Cox proportional hazards models examined the effect of relapses at different time periods (0 -5; Ͼ5-10; Ͼ10 years postonset) on time to cane (Expanded Disability Status Scale [EDSS]) and secondary progressive MS (SPMS). Findings were derived from hazard ratios with 95% confidence intervals (CIs), adjusted for sex, onset age, and symptoms.Results: Mean follow-up was 20.6 years; 11,722 postonset relapses were recorded. An early relapse (within 5 years postonset) was associated with an increased hazard in disease progression over the short term, by 48%; 95% CI 37%-60% for EDSS 6 and 29%; 95% CI 20%-38% for SPMS. However, this substantially lessened to 10%; 95% CI 4%-16% (EDSS 6) and 2%; 95% CI Ϫ2%-7% (SPMS) after 10 years postonset. The impact of later relapses (Ͼ5-10 years postonset) also lessened over time. Effects were modulated by age, impact being greatest in younger (Ͻ25 years at onset) and least in older (Ն35 years) patients where relapses beyond 5-years postonset typically failed to reach significance. Relapses during SPMS had no measurable impact on time to EDSS 6 from SPMS. Conclusion:Relapses within the first 5 years of disease impacted on disease progression over the short term. However, the long-term impact was minimal, either for early or later relapses. Long-term disease progression was least affected by relapses in patients with an extended disease duration (Ͼ10 years) or already in the secondary progressive phase. Neurology Multiple sclerosis (MS) is a common cause of neurologic disability in young adults.1 The majority (85%) present with a relapsing-remitting (RR) course, with many later entering the secondary progressive (SP) phase. Disability accrual in MS is said to occur in 2 situations: incomplete recovery from a relapse or deterioration of functional ability outside of a relapse, synonymous with the progressive phase. 1The mechanisms involved in either relapses or irreversible disability are not fully understood. Relapses are associated with inflammation and demyelination; irreversible disability with axonal damage. However, destruction of axons and the myelin-oligodendrocyte complex occurs in early and late disease.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methods Patientsmentioning

confidence: 99%

Section: Methods Patientsmentioning

confidence: 99%

Section: Methods Patientsmentioning

confidence: 99%

See 2 more Smart Citations

Impact of multiple sclerosis relapses on progression diminishes with time

Tremlett¹,

Yousefi²,

Devonshire³

et al. 2009

Neurology

207

172

View full text Add to dashboard Cite

show abstract

“…38–40 With a median time of 16.8 years since disease onset we would have anticipated that between 36% and 50% of the RMS patients would have developed SPMS, whereas only 11.3% of this cohort transitioned to SPMS during the course of the study. This transition rate of 1% annually is lower than reported from natural history studies but similar to a more recent retrospective analysis in an interferon-treated population.…”

Section: Discussionmentioning

confidence: 99%

Long‐term evolution of multiple sclerosis disability in the treatment era

Team:

2016

Annals of Neurology

367

167

View full text Add to dashboard Cite

Objectives To characterize the accrual of long-term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and MRI data used in clinical trials have long-term prognostic value. Methods This is a prospective study of 517 actively managed MS patients enrolled at a single center. Results More than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Score (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first two years had long-term outcomes that were no different from those of the cohort as a whole. 25-OH vitamin D serum levels were inversely associated with short-term MS disease activity; however, these levels had no association with long-term disability. At a median time of 16.8 years after disease onset, 10.7% (95% CI 7.2 to 14%) of patients reached an EDSS ≥6 and 18.1% (95% CI: 13.5 to 22.5%) evolved from relapsing MS (RMS) to secondary progressive MS (SPMS). Interpretations Rates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2-year endpoint was not a predictor of long-term stability. Finally, the data call into question the utility of annual MRI assessments as a treat-to-target approach for MS care.

show abstract

Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis

Shirani¹,

Zhao²,

Karim³

et al. 2012

JAMA

Self Cite

233

224

View full text Add to dashboard Cite

ULTIPLE SCLEROSIS (MS) IS a chronic disease that often affects people in the prime of their lives. A key feature of MS is clinical progression of the disease over time manifested by the accumulation of disability. Interferon beta drugs are the most widely prescribed disease-modifying drugs (DMDs) approved by the US Food and Drug Administration for the treatment of relapsing-onset MS, the most common MS disease course. Although a substantial reduction in brain lesion development, as evidenced by magnetic resonance imaging (MRI), 1 and a one-third relative reduction in relapse frequency were demonstrated in the pivotal clinical trials of interferon beta for relapsing-remitting MS, 2 there is a lack of well-controlled longitudinal studies investigating the effect of in-terferon beta on disability progression. Typically, drug efficacy (as established through randomized clinical trials conducted under optimal conditions) is greater than drug effectiveness (as measured in "real-world" settings). 3 Patients participating in clinical trials tend to be highly selected in For editorial comment see p 290.

show abstract

Natural history of secondary-progressive multiple sclerosis

Cited by 198 publications

References 38 publications

Impact of multiple sclerosis relapses on progression diminishes with time

Impact of multiple sclerosis relapses on progression diminishes with time

Long‐term evolution of multiple sclerosis disability in the treatment era

Association Between Use of Interferon Beta and Progression of Disability in Patients With Relapsing-Remitting Multiple Sclerosis

Contact Info

Product

Resources

About