Relapses and disability accumulation in progressive multiple sclerosis

Soldán, M. Mateo Paz; Novotná, Martina; Zeid, Nuhad Abou; Kale, Nilüfer; Tütüncü, Melih; Crusan, Daniel J.; Atkinson, Elizabeth J.; Síva, Aksel; Keegan, B. Mark; Pirko, Istvan; Pittock, Sean J.; Lucchinetti, Claudia F.; Weinshenker, Brian G.; Rodriguez, Moses; Kantarci, Orhun H.

doi:10.1212/wnl.0000000000001094

Cited by 96 publications

(96 citation statements)

References 41 publications

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“…Although most patients had some evidence of disease recurrence, either clinically or on CNS MRIs, during the 7 years of study, those with no evidence of disease activity for 2 years or more had a predictive value of 78.3% of remaining free of subsequent disease progression, a value slightly lower than noted in the present study but supporting the concept that in older persons with long-term acute disease quiescence, DMT may not be needed. Paz Soldan et al 9 studied patients with varying forms of progressive MS, both primary progressive MS and secondary progressive MS, in terms of the effects of relapses on disease progression. Their data suggested that after 5 years on DMT, or after age 55 years, the risk of relapses declined sufficiently that treatment could be stopped.…”

Section: Stopping Dmt In Nonrelapsing Msmentioning

confidence: 99%

Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis

Birnbaum¹

2017

International Journal of MS Care

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Background: Current disease-modifying therapies (DMTs) are of benefit only in people with relapsing forms of multiple sclerosis (RMS). Thus, safely stopping DMTs in people with secondary progressive MS may be possible. Methods: Two groups of patients with MS were studied. Group A consisted of 77 patients with secondary progressive MS and no evidence of acute central nervous system inflammation for 2 to 20 years. These patients were advised to stop DMTs. Group B consisted of 17 individuals with RMS who stopped DMTs on their own. Both groups were evaluated at treatment cessation and for a minimum of 1 year thereafter. Multiple variables were assessed to determine those that predicted recurrent acute disease. Results: Nine patients in group A (11.7%) and ten patients in group B (58.8%) had recurrent acute disease, almost always within 1 to 2 years of stopping treatment. The only variable of significance in group A distinguishing stable and relapsing patients was age (P = .0003), with relapsing patients being younger. Group B patients were younger and had significantly lower Expanded Disability Status Scale scores than group A, with no significant differences in age between relapsed and stable patients. Conclusions: The DMTs can be stopped safely in older patients with MS (≥7 decades) with no evidence of acute disease for 2 years or longer, with an almost 90% probability of remaining free of acute recurrence. The high proportion of untreated patients with RMS experiencing recurrent acute disease is consistent with published data.

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Section: Stopping Dmt In Nonrelapsing Msmentioning

confidence: 99%

Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis

Birnbaum¹

2017

International Journal of MS Care

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“…[9][10][11][12][13][14] Patients with relapsing forms of MS often develop progressive MS. 15 Secondary progressive MS (SPMS)…”

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confidence: 99%

“…Details of our study populations have been published. 14,15 We studied 2 independent populations representing population-based as well as clinic-based ascertainment of patients with MS fulfilling McDonald diagnostic criteria 29,30 (figure 1). The population-based cohort was nested within the original MS cohort from Olmsted County, MN, based on availability of relapse recovery information.…”

mentioning

confidence: 99%

“…The clinic-based cohort was nested within the previously published clinic-based progressive MS cohort (original cohort size: 106 SAPMS, 341 SPMS, 307 PPMS) seen between 2003 and 2007 (inclusive). 14,15 This cohort enriched for the less common SAPMS form of MS. Since our outcome was the onset of progressive MS following relapses, patients with PPMS were excluded from both cohorts.…”

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confidence: 99%

“…Typical of a standard clinical practice setting, the most rigorous historical documentation and clinical examination closest in time to progressive MS onset was used to establish the date of progressive MS onset. 14,15 Study variables. We extracted the following data: sex, age at MS onset, syndrome at MS onset, whether a relapse was fulminant, number of relapses occurring within the first 5 years of MS onset or until last follow-up or until progressive MS onset (whichever came first), amount of recovery and time to maximum recovery from all individual relapses within the first 5 years, disease-modifying drug (DMD) use duration (as percent duration of the time to progressive MS onset), number of DMDs used until progressive MS onset (as a secondary measure of disease activity level), and age at progressive MS onset.…”

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confidence: 99%

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Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

2015

Neurology

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Objective: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). Methods:We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured $6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test).Results: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p 5 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p , 0.001). A brainstem, cerebellar, or spinal cord syndrome (p 5 0.001) or a fulminant relapse (p , 0.0001) was associated with a poor recovery from the initial relapse. In multiple sclerosis (MS), the ability of some patients to recover faster and better than others is an important but poorly understood observation. Predictors of incomplete recovery are older patient age, location, and severity or duration of relapse. Conclusions:1-6 Each relapse carries a risk of irreversible myelin and axonal loss determined by the extent and duration of the injury and inherent ability to recover. 7,8 Time to maximum recovery is believed to be associated with duration of pathogenic immunologic processes. 6 Early remyelination is likely important in determining the extent of recovery.Progressive disease course is characterized by insidious and irreversible accumulation of neurologic disability, with or without superimposed relapses or ongoing MRI activity.9-14 Patients with relapsing forms of MS often develop progressive MS.15 Secondary progressive MS (SPMS) †Deceased.

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Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome

et al. 2021

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IMPORTANCEYounger age, oligoclonal bands, and infratentorial and spinal cord lesions are factors associated with an increased 10-year risk of clinical conversion from radiologically isolated syndrome (RIS) to multiple sclerosis (MS). Whether disease-modifying therapy is beneficial for individuals with RIS is currently unknown. OBJECTIVES To evaluate the 2-year risk of a clinical event (onset of clinical symptoms of MS) prospectively, identify factors associated with developing an early clinical event, and simulate the sample size needed for a phase III clinical trial of individuals with RIS meeting 2009 RIS criteria. DESIGN, SETTING, AND PARTICIPANTS This cohort study used data on prospectively followed-up individuals with RIS identified at 1 of 26 tertiary centers for MS care in France that collect data for the Observatoire Français de la Sclérose en Plaques database. Participants were aged 10 to 80 years with 2 or more magnetic resonance imaging (MRI) scans after study entry and an index scan after 2000. All diagnoses were validated by an expert group, whose review included a double centralized MRI reading. Data were analyzed from July 2020 to January 2021. EXPOSURE Diagnosis of RIS. MAIN OUTCOMES AND MEASURES Risk of clinical event and associated covariates at index scan were analyzed among all individuals with RIS. Time to the first clinical event was compared by covariates, and sample size estimates were modeled based on identified risk factors. RESULTS Among 372 individuals with RIS (mean [SD] age at index MRI scan, 38.6 [12.1] years), 354individuals were included in the analysis (264 [74.6%] women). A clinical event was identified among 49 patients (13.8%) within 2 years, which was associated with an estimated risk of conversion of 19.2% (95% CI, 14.1%-24.0%). In multivariate analysis, age younger than 37 years (hazard ratio [HR], 4.04 [95% CI, 2.00-8.15]; P < .001), spinal cord lesions (HR, 5.11 [95% CI,]; P = .001), and gadolinium-enhancing lesions on index scan (HR, 2.09 [95% CI, 1.13-3.87]; P = .02) were independently associated with an increased risk of conversion to MS. Having 2 factors at the time of the index MRI scan was associated with a risk of 27.9% (95% CI, 13.5%-39.9%) of a seminal event within 2 years, increasing to 90.9% (95% CI, 41.1%-98.6%) for individuals with all 3 factors (3 risk factors vs none: HR, 23.34 [95% CI, 9.08-59.96]; P < .001). Overall, with 80% power to detect an effect size of 60% within 24 months, a total of 160 individuals with RIS were needed assuming an event rate of 20%. (continued) Key Points Question Are there clinical or demographic factors associated with time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome? Findings In this cohort study of 372 individuals with radiologically isolated syndrome, young age, the presence of spinal cord lesions, and gadoliniumenhancing lesions on the index magnetic resonance imaging scan were associated with increased risk of onset of clinical symptoms of multiple sclerosis. Meaning Thes...

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Relapses and disability accumulation in progressive multiple sclerosis

Cited by 96 publications

References 41 publications

Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis

Stopping Disease-Modifying Therapy in Nonrelapsing Multiple Sclerosis

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

Risk Factors and Time to Clinical Symptoms of Multiple Sclerosis Among Patients With Radiologically Isolated Syndrome

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