Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors

2020 ◽  
pp. 135245852097436
Author(s):  
Pietro Iaffaldano ◽  
Giuseppe Lucisano ◽  
Francesco Patti ◽  
Vincenzo Brescia Morra ◽  
Giovanna De Luca ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Protective Factor ◽  
Cox Regression ◽  
Age At Onset ◽  
Progressive Multiple Sclerosis ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Definition Of ◽  
Relapsing Remitting Multiple Sclerosis

Background: No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). Methods: Relapsing-onset MS patients ( n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. Results: SPMS identified by the DDA ( n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( p < 0.0001), than those identified by the ND ( n = 3868, 20.0%). In both groups, the most consistent risk factors ( p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.

scholarly journals Use and cost of disease-modifying therapies by Sonya Slifka Study participants: has anything really changed since 2000 and 2009?

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731882088 ◽  
Author(s):  
Sarah L Minden ◽  
R Philip Kinkel ◽  
Helene T Machado ◽  
Jonathan S Levin ◽  
Meredith B Rosenthal ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family Income ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies benefit individuals with relapsing forms of multiple sclerosis, but their utility remains unclear for those without relapses. Objective To determine disease-modifying therapy use and costs in 2009, compare use in 2009 and 2000, and examine compliance with evidence-based guidelines. Methods We determined the extent and characteristics of disease-modifying therapy use by participants in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka) in 2000 ( n=2156) and 2009 ( n=2361) and estimated out-of-pocket and total (payer) costs for 2009. Two multivariable logistic regressions predicted disease-modifying therapy use. Results Disease-modifying therapy use increased from 55.3% in 2000 to 61.5% in 2009. In 2009, disease-modifying therapy use was reported by 76.5% of participants with relapsing-remitting multiple sclerosis, 73.2% with progressive-relapsing multiple sclerosis, 62.5% with secondary progressive multiple sclerosis, and 41.8% with primary progressive multiple sclerosis. Use was significantly associated with relapsing-remitting multiple sclerosis, shorter duration of illness, one to two relapses per year, non-ambulatory symptoms, using a cane, younger age, higher family income, and having health insurance. Average annual costs in 2009 were US$939–3101 for patients and US$16,302–18,928 for payers. Conclusion Use rates were highest for individuals with relapsing-remitting multiple sclerosis, but substantial for those with progressive courses although clinical trials have not demonstrated significant benefits for them.

scholarly journals Exploring polypharmacy phenomenon in newly diagnosed relapsing–remitting multiple sclerosis: a cohort ambispective single-centre study

2021 ◽  
Vol 12 ◽  
pp. 204062232098312
Author(s):  
Aurora Zanghì ◽  
Emanuele D’Amico ◽  
Salvatore Lo Fermo ◽  
Francesco Patti
Keyword(s):  
Multiple Sclerosis ◽  
Age At Onset ◽  
Rank Test ◽  
Multinomial Regression ◽  
Single Centre ◽  
Centre Study ◽  
Relapsing Remitting ◽  
Single Centre Study ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Aims: We aimed to examine the frequency of polypharmacy in a large cohort of patients at the time of diagnosis of relapsing–remitting multiple sclerosis (RRMS) and to explore its effects on discontinuation of first disease-modifying treatment (DMT) using survival analysis. Methods: This was a cohort ambispective single-centre study. We enrolled RRMS patients starting their first DMT between 1st January 2013 and 31st December 2015. According to the number of medicines prescribed (except DMTs), we divided the patients into three groups: no-poly RRMS, minor-poly RRMS (from one to three medications), and major-poly RRMS (more than three medications). Results: A total of 392 RRMS patients were enrolled (mean age 41.1). The minor-poly RRMS group included 61 patients (15.6%) and the major-poly RRMS group included 112 (28.6%). Individuals in these groups were older and had higher median body mass index (BMI) than patients in the no-poly RRMS group ( p < 0.05). Upon multinomial regression analysis, older age at onset was associated with minor and major polypharmacy (OR 1.050, CI 1.010–1.093, p = 0.015 and OR 1.063, CI 1.026–1.101, p = 0.001, respectively) and higher BMI was associated with major polypharmacy (OR 1.186, CI 1.18–1.29, p = 0.001). The rates of discontinuation of first DMT were similar among the three groups (50.7% for no-Poly RRMS, 50.8% for minor-Poly RRMS, and 53.3% for major-Poly RRMS, p = 0.264). At log-Rank test, there were no differences among the three groups ( p = 0.834). Conclusion: Polypharmacy was more common in older RRMS patients with high BMI.

scholarly journals Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Change ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Serial Addition ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

scholarly journals Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment

2017 ◽  
Vol 24 (4) ◽  
pp. 472-480 ◽  
Author(s):  
Cyra E Leurs ◽  
Petar Podlesniy ◽  
Ramon Trullas ◽  
Lisanne Balk ◽  
Martijn D Steenwijk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Neurologic Disease ◽  
Brain Volumes ◽  
Multiple Sclerosis Disease ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Digital Polymerase Chain Reaction

Background: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response. Objectives: To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes. To explore the effect of disease-modifying therapies on mtDNA levels in the CSF. Methods: CSF mtDNA was measured using a digital polymerase chain reaction (PCR) CSF mtDNA in two independent MS cohorts. The cohorts included 92 relapsing-remitting multiple sclerosis (RRMS) patients, 40 progressive multiple sclerosis (PMS) patients (27 secondary progressive and 13 primary progressive), 50 various neurologic disease controls, and 5 healthy controls. Results: Patients with PMS showed a significant increase in CSF mtDNA compared to non-inflammatory neurologic disease controls. Patients with higher T2 lesion volumes and lower normalized brain volumes showed increased concentration of mtDNA. Patients treated with fingolimod had significantly lower mtDNA copy levels at follow-up compared to baseline. Conclusion: Our results showed a non-specific elevation of concentration of mtDNA in PMS patients. mtDNA concentrations respond to fingolimod and may be used to monitor biological effect of this treatment.

scholarly journals Onset of secondary progressive multiple sclerosis is not influenced by current relapsing multiple sclerosis therapies

2018 ◽  
Vol 4 (2) ◽  
pp. 205521731878334 ◽  
Author(s):  
Francisco Coret ◽  
Francisco C Pérez-Miralles ◽  
Francisco Gascón ◽  
Carmen Alcalá ◽  
Arantxa Navarré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Secondary Progressive ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background Disease-modifying therapies are thought to reduce the conversion rate to secondary progressive multiple sclerosis. Objective To explore the rate, chronology, and contributing factors of conversion to the progressive phase in treated relapsing–remitting multiple sclerosis patients. Methods Our study included 204 patients treated for relapsing–remitting multiple sclerosis between 1995 and 2002, prospectively followed to date. Kaplan–Meier analysis was applied to estimate the time until secondary progressive multiple sclerosis conversion, and multivariate survival analysis with a Cox regression model was used to analyse prognostic factors. Results Relapsing–remitting multiple sclerosis patients were continuously treated for 13 years (SD 4.5); 36.3% converted to secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range 17.1–18.1). A multifocal relapse, age older than 34 years at disease onset and treatment failure independently predicted conversion to secondary progressive multiple sclerosis but did not influence the time to reach an Expanded Disability Status Scale of 6.0. Conclusions The favourable influence of disease-modifying therapies on long-term disability in relapsing–remitting multiple sclerosis is well established. However, the time to progression onset and the subsequent clinical course in treated patients seem similar to those previously reported in natural history studies. More studies are needed to clarify the effect of disease-modifying therapies once the progressive phase has been reached.

Risk factors for lymphopenia in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate

2019 ◽  
Vol 267 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Fabian Sierra Morales ◽  
Igor J. Koralnik ◽  
Shiva Gautam ◽  
Soleil Samaan ◽  
Jacob A. Sloane
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Dimethyl Fumarate ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

scholarly journals Ocrelizumab-induced alopecia areata—A series of five patients from Ontario, Canada: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2091961
Author(s):  
Laura D Chin ◽  
Mohn’d AbuHilal
Keyword(s):  
Multiple Sclerosis ◽  
Alopecia Areata ◽  
Conventional Treatment ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Cd20 Antigen ◽  
Humanized Monoclonal Antibody ◽  
Relapsing Remitting ◽  
Topical Minoxidil ◽  
Relapsing Remitting Multiple Sclerosis

Background: Ocrelizumab is a humanized monoclonal antibody that targets the CD20 antigen found on B-cells. It is indicated in the treatment of both relapsing–remitting multiple sclerosis and primary progressive multiple sclerosis. Objective: The aim of this study is to report and describe the characteristics of alopecia areata following treatment with ocrelizumab for multiple sclerosis. Results: Five patients were reported, two female and three male. Four of the five patients had alopecia areata of the scalp, one of the five having alopecia to the beard area. All patients responded well to conventional treatment with topical and intralesional corticosteroids and topical minoxidil foam. Ocrelizumab can be associated with the development of alopecia areata. Initiation of proper treatment may lead to quick improvement or resolution of this potentially reversible adverse effect.

Progressive Cerebellar Ataxia After Natalizumab Treatment

2021 ◽  
pp. 65-68
Author(s):  
Michel Toledano
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Polyoma Virus ◽  
Resonance Imaging ◽  
Disease Modifying Therapy ◽  
Relapsing Remitting ◽  
Disease Modifying ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

A 47-year-old woman with a history of relapsing-remitting multiple sclerosis (MS) receiving natalizumab therapy sought a second opinion regarding a recent diagnosis of secondary progressive disease. She was first diagnosed with multiple sclerosis 8 years earlier. While taking natalizumab, she was monitored for the development of antibodies to JC polyoma virus. Nine months before our evaluation, anti-JC polyoma virus antibodies became positive, with an increased index of 1.1. Given sustained remission, she was continued on natalizumab with increased surveillance and a plan to switch to a different disease-modifying therapy after 24 months. Five months later she noted subacute onset of slurred speech and right upper extremity incoordination. Over the next 4 months she continued to have clinical decline. On examination she had moderate ataxic dysarthria and right greater than left appendicular ataxia. She relied on a wheelchair for transportation and required 1-person assist to stand. Reflexes were brisk with bilateral Babinski sign. This patient with relapsing-remitting multiple sclerosis on natalizumab had a new subacute progressive cerebellar syndrome without radiographic evidence of disease activity. Repeated magnetic resonance imaging showed worsening cerebellar atrophy, right sided greater than left sided, and evolving T2 hyperintensity in the brainstem without enhancement or mass effect. JC polyoma virus polymerase chain reaction was positive. The patient was diagnosed with JC polyoma virus granule cell neuronopathy. Natalizumab was discontinued, and she was treated with 4 of 5 planned cycles of plasma exchange. After her 4th cycle, worsening symptoms developed. Magnetic resonance imaging showed gadolinium enhancement in the brainstem supportive of immune reconstitution inflammatory syndrome. She received high-dose intravenous methylprednisolone followed by a prednisone taper. Her disability progression stabilized. JC polyoma virus central nervous system infection, 1 of several infections reported among treated patients with multiple sclerosis, occurs almost exclusively in immunosuppressed patients, including those receiving disease-modifying therapy for multiple sclerosis.

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