Yaroslavl State Medical University
Neurology

Author Of 3 Presentations

Clinical Outcome Measures Poster Presentation

P0113 - MRI activity as a predictor of suboptimal response to natalizumab treatment: single center prospective cohort trial (ID 850)

Speakers
Presentation Number
P0113
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Second line disease modifying drugs are widely used in clinical practice, the most common is natalizumab. NTZ have usually reduced the annualized rate of relapse and MRI lesion load in clinical trials but sometimes clinical and MRI activity was still present. Defining the predictors of suboptimal response is still needed to decide which second line treatment drug is optimal for patient.

Objectives

To determine the early clinical and MRI predictors of suboptimal treatment responses at one year of natalizumab (NTZ) therapy.

Methods

Clinical assessment (EDSS, relapses) and MRI (T2, T1Gd+) on start, after 6 and 12 months were made. All patients receive NTZ as second line therapy. RRMS patients undergoing treatment with NTZ for at least 12 months were classified as optimal responders if they have no EDSS score increase, no relapses and stable MRI (<3 new T2 and no Gd+(GELs)).Statistical analysis: one-way ANOVA, ROC-curve.

Results

43 patients (34 female) were included in analysis, RRMS, age–35.9-41.6 (95%CI) years, with disease duration of 58-131(95%CI) months;25-31(95%CI) NTZ infusions. On month 12 30.2% have a suboptimal response: 3 patient have a clinical relapse, 4–increasing of EDSS, 13–MRI activity. The comparison of the groups did not reveal statistically significant differences in age, sex, duration of the disease, duration of therapy before starting NTZ, relapse rate on baseline. Patients in suboptimal response group have more severe previous year MRI activity (before NTZ): more severe T2 lesion load (F=6.3,p=0.016) and high number of GELs (F=4.1,p=0.051). Predictors of suboptimal response are: more than 4 new T2 lesions during last year and more than 2 GELs on MRI before NTZ.

Conclusions

High previous year MRI activity is a strong predictor of suboptimal NTZ response. This cohort of patients probably needs more powerful therapy, for example, alemtuzumab or cladribine.

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Epidemiology Poster Presentation

P0468 - Increasing Frequency of Multiple Sclerosis in Yaroslavl, Russia: A 20 Year Epidemiological Survey (ID 1002)

Speakers
Presentation Number
P0468
Presentation Topic
Epidemiology

Abstract

Background

The epidemiology of MS is rapidly changing in many parts of the world. Since 1990s, many epidemiological studies have classified Russia as a low-moderate-risk area for MS. Changes in the availability of MRI and the organization of specialized care services have led to a significant improvement in the diagnosis of the disease. The introduction of a disease modifying therapy support system has also made a significant contribution to the changing of the epidemiology. Yaroslavl is a city and the administrative center of Yaroslavl Oblast, Russia, located 250 kilometers (160 mi) northeast of Moscow, medium size industrial city with nearly 600,000 residents.

Objectives

to determine the difference in prevalence and incidence rates of MS and clinical representation in 1999 and 2019 in city of Yaroslavl (Central Russia region).

Methods

This cross-sectional study was conducted between 1997 and 2020. Patients with a diagnosis of MS according to 1993 Poser criteria (1999, with MRI control) and 2010 revised McDonald criteria (2019) were identified. Prevalence was defined as the total number of patients with a diagnosis of MS per 100,000 inhabitants, while the incidence was defined as the number of new cases diagnosed with MS per 100,000 individuals. All rates were calculated with emphasis on age range and gender, standardized by European population.

Results

Two hundred and fifty-seven patients with MS who had experienced the clinical onset of the disease before 31 December 1999 and 479 patients with onset before 31 December 2019 were found. The prevalence rate was 42.6/100,000 [95% confidence interval (CI) 40.3–45.0] and 72,3/100,000 (95% CI 69.8-75.2), respectively (+84%, p=0.002). The mean annual prevalence from 1995 to 1999 was 1,6 (95% CI 1.4-1.9). From 2014 to 2018, 109 patients with MS had clinical onset of the disease. The mean annual incidence was 3.3/100,000 (95% CI 2.7–4.1), so we have a 207 per cent growth. Sex ratio (male:female) is also changed from 1,52:1 to 2,49:1 The mean length of time between the date of clinical onset and the date of the diagnosis was 1.4 ± 1.7 years. Symptoms of MS onset changed from motor (47.4%) and optic neuropathy (16.8%) in 1999 to optic (25.3%) and brainstem (20.6%) in 2019.

Conclusions

Incidence rates have further increased in Yaroslavl population, suggesting that the risk of MS is still increasing. Now Yaroslavl city approaching to be considered a high-risk area for MS.

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Comorbidities Poster Presentation

P0492 - Selective serotonin-reuptake inhibitors as potential add-on agents in relapsing-remitting multiple sclerosis patients with suboptimal response (ID 1004)

Speakers
Presentation Number
P0492
Presentation Topic
Comorbidities

Abstract

Background

Suboptimal response for first line treatment of multiple sclerosis (MS) is one of the main challenges for real clinical practice. Presence of subthreshold activity suggests the possibility of switching to the second line of therapy, however, this is not always possible due to various reasons. Suboptimal response also could lead to increasing of patient’s reactive depression.

Objectives

To define the possibility of using SSRI (duloxetine or fluoxetine) for patients with suboptimal response on first-line injectable disease modifying therapy (DMT) to optimize response rate.

Methods

Clinical evaluation (EDSS, relapses), depression (Beck), MRI (T2&T1). Statistical analysis (nonparametric) – Wilkoxon test, Sign test. Inclusion criteria: 1) relapsing-remitting MS, 2) interferon beta (IFN) or glatiramer acetate (GA) during last 12 months, 3) suboptimal response for therapy defined by modified Rio Score (1 relapse during previous year without MRI activity OR +4-6 T2 lesions on MRI during previous year), 4) mild or moderate depression. Exclusion criteria: 1) progressive MS, 2) nonresponse defined by modified Rio Score and indication for switch to 2nd line, 3) severe depression, 4) severe comorbidity. Study design: visit 1 – baseline (EDSS, previous year relapses, MRI, depression scale), starting SSRI (duloxetine or fluoxetine); visit 2 – 1 year on SSRI + previous DMT (EDSS, previous year relapses, MRI, depression scale).

Results

Seventy patients (56 females), relapsing-remitting MS, age – 35,2 years [Q1:Q3; 28:42], duration of disease – 4,2 years [2:10], EDSS at visit 0 – 3.0 [2.4:3.6], DMT (GA–20, IFNb1b–30, IFNb1a–20) who met criteria at visit 1. Baseline relapse rate was 0.65 [95% confidence interval (CI) 0.61-0.70], dynamics of T2 lesion load during previous year +3.57 lesion [95%CI 2.6-4.8], EDSS dynamics during previous year - +0.27 [95%CI 0.24-0.31]. After 1 year of combined therapy (DMT+SSRI) relapse rate significantly decreased - 0.2 (T=180, p<0.001), no significant increase of EDSS level – minus 0.36 points. MRI activity also significantly decrease: numbers of new or newly enlarging T2 lesions were significantly reduced compared with the previous year: T2 lesion load increase only by 0.4 [95%CI 0.3-0.5] (T=51, p<0.001).

Conclusions

Adding SSRI (duloxetine or fluoxetine) to standard first line DMT for patients with suboptimal response could improve the response to the main DMT without switching to 2nd line.

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Presenter Of 3 Presentations

Clinical Outcome Measures Poster Presentation

P0113 - MRI activity as a predictor of suboptimal response to natalizumab treatment: single center prospective cohort trial (ID 850)

Speakers
Presentation Number
P0113
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Second line disease modifying drugs are widely used in clinical practice, the most common is natalizumab. NTZ have usually reduced the annualized rate of relapse and MRI lesion load in clinical trials but sometimes clinical and MRI activity was still present. Defining the predictors of suboptimal response is still needed to decide which second line treatment drug is optimal for patient.

Objectives

To determine the early clinical and MRI predictors of suboptimal treatment responses at one year of natalizumab (NTZ) therapy.

Methods

Clinical assessment (EDSS, relapses) and MRI (T2, T1Gd+) on start, after 6 and 12 months were made. All patients receive NTZ as second line therapy. RRMS patients undergoing treatment with NTZ for at least 12 months were classified as optimal responders if they have no EDSS score increase, no relapses and stable MRI (<3 new T2 and no Gd+(GELs)).Statistical analysis: one-way ANOVA, ROC-curve.

Results

43 patients (34 female) were included in analysis, RRMS, age–35.9-41.6 (95%CI) years, with disease duration of 58-131(95%CI) months;25-31(95%CI) NTZ infusions. On month 12 30.2% have a suboptimal response: 3 patient have a clinical relapse, 4–increasing of EDSS, 13–MRI activity. The comparison of the groups did not reveal statistically significant differences in age, sex, duration of the disease, duration of therapy before starting NTZ, relapse rate on baseline. Patients in suboptimal response group have more severe previous year MRI activity (before NTZ): more severe T2 lesion load (F=6.3,p=0.016) and high number of GELs (F=4.1,p=0.051). Predictors of suboptimal response are: more than 4 new T2 lesions during last year and more than 2 GELs on MRI before NTZ.

Conclusions

High previous year MRI activity is a strong predictor of suboptimal NTZ response. This cohort of patients probably needs more powerful therapy, for example, alemtuzumab or cladribine.

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Epidemiology Poster Presentation

P0468 - Increasing Frequency of Multiple Sclerosis in Yaroslavl, Russia: A 20 Year Epidemiological Survey (ID 1002)

Speakers
Presentation Number
P0468
Presentation Topic
Epidemiology

Abstract

Background

The epidemiology of MS is rapidly changing in many parts of the world. Since 1990s, many epidemiological studies have classified Russia as a low-moderate-risk area for MS. Changes in the availability of MRI and the organization of specialized care services have led to a significant improvement in the diagnosis of the disease. The introduction of a disease modifying therapy support system has also made a significant contribution to the changing of the epidemiology. Yaroslavl is a city and the administrative center of Yaroslavl Oblast, Russia, located 250 kilometers (160 mi) northeast of Moscow, medium size industrial city with nearly 600,000 residents.

Objectives

to determine the difference in prevalence and incidence rates of MS and clinical representation in 1999 and 2019 in city of Yaroslavl (Central Russia region).

Methods

This cross-sectional study was conducted between 1997 and 2020. Patients with a diagnosis of MS according to 1993 Poser criteria (1999, with MRI control) and 2010 revised McDonald criteria (2019) were identified. Prevalence was defined as the total number of patients with a diagnosis of MS per 100,000 inhabitants, while the incidence was defined as the number of new cases diagnosed with MS per 100,000 individuals. All rates were calculated with emphasis on age range and gender, standardized by European population.

Results

Two hundred and fifty-seven patients with MS who had experienced the clinical onset of the disease before 31 December 1999 and 479 patients with onset before 31 December 2019 were found. The prevalence rate was 42.6/100,000 [95% confidence interval (CI) 40.3–45.0] and 72,3/100,000 (95% CI 69.8-75.2), respectively (+84%, p=0.002). The mean annual prevalence from 1995 to 1999 was 1,6 (95% CI 1.4-1.9). From 2014 to 2018, 109 patients with MS had clinical onset of the disease. The mean annual incidence was 3.3/100,000 (95% CI 2.7–4.1), so we have a 207 per cent growth. Sex ratio (male:female) is also changed from 1,52:1 to 2,49:1 The mean length of time between the date of clinical onset and the date of the diagnosis was 1.4 ± 1.7 years. Symptoms of MS onset changed from motor (47.4%) and optic neuropathy (16.8%) in 1999 to optic (25.3%) and brainstem (20.6%) in 2019.

Conclusions

Incidence rates have further increased in Yaroslavl population, suggesting that the risk of MS is still increasing. Now Yaroslavl city approaching to be considered a high-risk area for MS.

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Comorbidities Poster Presentation

P0492 - Selective serotonin-reuptake inhibitors as potential add-on agents in relapsing-remitting multiple sclerosis patients with suboptimal response (ID 1004)

Speakers
Presentation Number
P0492
Presentation Topic
Comorbidities

Abstract

Background

Suboptimal response for first line treatment of multiple sclerosis (MS) is one of the main challenges for real clinical practice. Presence of subthreshold activity suggests the possibility of switching to the second line of therapy, however, this is not always possible due to various reasons. Suboptimal response also could lead to increasing of patient’s reactive depression.

Objectives

To define the possibility of using SSRI (duloxetine or fluoxetine) for patients with suboptimal response on first-line injectable disease modifying therapy (DMT) to optimize response rate.

Methods

Clinical evaluation (EDSS, relapses), depression (Beck), MRI (T2&T1). Statistical analysis (nonparametric) – Wilkoxon test, Sign test. Inclusion criteria: 1) relapsing-remitting MS, 2) interferon beta (IFN) or glatiramer acetate (GA) during last 12 months, 3) suboptimal response for therapy defined by modified Rio Score (1 relapse during previous year without MRI activity OR +4-6 T2 lesions on MRI during previous year), 4) mild or moderate depression. Exclusion criteria: 1) progressive MS, 2) nonresponse defined by modified Rio Score and indication for switch to 2nd line, 3) severe depression, 4) severe comorbidity. Study design: visit 1 – baseline (EDSS, previous year relapses, MRI, depression scale), starting SSRI (duloxetine or fluoxetine); visit 2 – 1 year on SSRI + previous DMT (EDSS, previous year relapses, MRI, depression scale).

Results

Seventy patients (56 females), relapsing-remitting MS, age – 35,2 years [Q1:Q3; 28:42], duration of disease – 4,2 years [2:10], EDSS at visit 0 – 3.0 [2.4:3.6], DMT (GA–20, IFNb1b–30, IFNb1a–20) who met criteria at visit 1. Baseline relapse rate was 0.65 [95% confidence interval (CI) 0.61-0.70], dynamics of T2 lesion load during previous year +3.57 lesion [95%CI 2.6-4.8], EDSS dynamics during previous year - +0.27 [95%CI 0.24-0.31]. After 1 year of combined therapy (DMT+SSRI) relapse rate significantly decreased - 0.2 (T=180, p<0.001), no significant increase of EDSS level – minus 0.36 points. MRI activity also significantly decrease: numbers of new or newly enlarging T2 lesions were significantly reduced compared with the previous year: T2 lesion load increase only by 0.4 [95%CI 0.3-0.5] (T=51, p<0.001).

Conclusions

Adding SSRI (duloxetine or fluoxetine) to standard first line DMT for patients with suboptimal response could improve the response to the main DMT without switching to 2nd line.

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