CHU de Nice - Hopital Pasteur 2
CRC SEP - Service de Neurologie

Author Of 1 Presentation

Neuromyelitis Optica and Anti-MOG Disease Oral Presentation

YI02.04 - Comparison of clinical characterization, risk of relapses and antibody dynamics between children and adults with MOGAD

Abstract

Background

To predict the clinical course of myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is essential to guide treatment recommendations.

Objectives

We aimed to 1) compare clinical features and disease course, and 2) to evaluate the association of MOG-Ab dynamics and relapses, between children and adults with MOGAD.

Methods

Retrospective study evaluating clinical features of 98 children and 266 adults with MOGAD, between January 2014 and September 2019. To analyse relapses over the whole disease course, a Cox regression analysis for recurrent time-to-event data was performed, introducing treatment as time-dependent covariate. To evaluate dynamics, delta mean fluorescence intensity ratio signal (ΔMFIratio) of MOG-Ab was measured in patients with a minimum time elapsed between two samples of 4 months.

Results

Median age at onset of symptoms was 10.9 (interquartile range 5.4-14.3) years in children and 36.2 (27.7-47.6) in adults. Isolated optic neuritis was the most frequent clinical presentation both in children (40.8%) and adults (55.9%), p=0.013, and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs. 5.6%; p<0.001). Compared to adults, children displayed a better recovery (EDSS ≥3.0 at last follow-up reached only by 10 of 97 [10.3%] vs. 66/247 [26.7%], p<0.001).

In the multivariate analysis, adults were at higher risk of relapse than children (Hazard ratio 1.41, 95%Confidence interval [CI] 1.12-1.78; p=0.003). Among the 124 participants evaluated for MOG-Ab dynamics, 36.3% became seronegative, 60.5% decrease and 3.2% increase the ΔMFIratio. At two years, 64.2% (95%CI 40.9-86.5) of non-relapsing children became MOG-Ab negative compared to 14.1% (95%CI 4.7-38.3) of relapsing ones, log-rank p<0.001, with no differences observed between non-relapsing and relapsing adults, log-rank p=0.280.

Conclusions

MOGAD differs in its clinical presentation at onset, showing a progressive shift in the clinical features across age-groups. Compared to children, adults have a higher risk of relapses and a worse functional recovery. Finally, children with monophasic disease became MOG-Ab negative earlier than relapsing ones, but not in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults.

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Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0034 - Can Digital Biomarkers Acquired on a Smarphone Distinguish Healthy Controls from Radiologically Isolated Syndrome Subjects? (ID 238)

Speakers
Presentation Number
P0034
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Radiologically isolated syndrome (RIS) is defined by the incidental finding of MRI lesions suggestive of multiple sclerosis in subjects with a normal neurological examination. Some studies suggested that the use of wearables could unveil infra-clinical differences between RIS subjects and healthy controls (HC).

Objectives

To demonstrate that digital biomarkers collected by a smartphone application can distinguish healthy controls (HC) from subjects with radiologically isolated syndrome (RIS).

Methods

We created a mobile app called MS Screen Test (MSST) that contains:

- Finger tapping speed test: during this task, we measure the mean tapping speed for the dominant hand and the non dominant hand

- Level test: the subject is asked to tilt the phone to move a ball inside a target, then maintain it inside the target for 10 seconds. We measure the required time to bring the ball to the target, then the proportion of time during which the ball is maintained inside the target

- Low contrast vision (LCV) test: letters with varying contrast randomly appearing on the screen. The subject has to tap on the screen each time a letter is seen. The number of good answers is collected

- Cognition test: letters or digits randomly appear on the screen. The subject has to tap on the screen only if a letter is seen. The mean tap latency in milliseconds is collected as well as bad answers

A cohort of HC and RIS subjects were evaluated to compare performances on MSST.

Results

60 HC and 16 RIS subjects were prospectively included (F/M 3.15, mean age 41.6 yrs)

Compared to HC, RIS subjects had a lower tapping speed on both dominant (5.6 Hz vs 6.5 Hz, p=0.001) and non dominant hand (5.1 Hz vs 5.6 Hz, p=0.04), fewer detected letters on the LCV test (10 vs 13, p=0.001) and a higher latency of response on the cognitive test (731 ms vs 599 ms, p<0.0001).

On the level test, the time during which the ball was maintained is the target was shorter for RIS subjects (3 sec vs 4.9 sec, p=0.05).

Conclusions

Our study confirms that digital biomarkers collected by a smartphone can unveil differences between HC and subjects at a presymptomatic stage of MS.

It would be relevant to evaluate whether those biomarkers could predict the risk of conversion to multiple sclerosis, as well as to evaluate their potential predictive value in early diagnosed MS patients

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Clinical Trials Poster Presentation

P0193 - BEST-MS: A standardized and prospective study comparing the efficacy of natalizumab versus fingolimod in active relapsing multiple sclerosis (ID 237)

Abstract

Background

Therapeutic options are growing for active RRMS patients, however, few prospective studies are available to compare the efficacy of those treatments. Best Escalation Strategy in MS (BEST MS) started in France in 2013 when natalizumab (NTZ) and fingolimod (FTY) were the two most employed second-line therapies in active RRMS.

Objectives

To compare the efficacy between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting multiple sclerosis (RRMS).

Methods

BEST-MS is a French prospective multicentric study.

Patients with active RRMS (defined as at least 1 relapse in the last 12 months on a well-conducted 1st line treatment with at least 9 T2 hyperintensities on MRI, OR at least 2 relapses in the last 12 months with evidence of active disease on MRI for naïve patients) were enrolled to be treated either with NTZ or FTY. Treatments choice was at the discretion of the physician.

Relapses, EDSS and brain MRI were collected at baseline and at 12 months.

The main outcome measure was the proportion of patients reaching No Evidence of Disease Activity (NEDA) at 12 months, defined as the absence of relapses, absence of new T2 lesions, absence of new gadolinium enhancing lesions and a stable EDSS score.

Results

230 patients were included (age: 38.2 yrs, F/M: 3.1, FTY: 117, NTZ: 113). There was no statistical difference between groups regarding baseline characteristics.

Treatment drop out rate was higher in FTY group (22% vs 12%, p<0.0001) and most of thoses cases were related to a lack of efficacy.

At M12, 43% of patients treated with NTZ reached NEDA versus 27% in the FTY group (p=0.04)

NTZ indicated a better efficacy regarding new T2 lesions (0.7 vs 1.4, p=0.01) and gadolinium enhancing lesions (0.03 vs 0.5, p<0.0001).

Relapse rate (ARR) was lower in NTZ group (0.2 vs 0.27, p = 0.04), even if most relapses occurred during the first 4 months of treatment in both groups.

Conclusions

NTZ showed higher efficacy than FTY on MRI in active RRMS patients. ARR was also lower in favor of NTZ, but most relapses occurred early. However, the rate of drop out was higher for patients treated with FTY.

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Presenter Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0034 - Can Digital Biomarkers Acquired on a Smarphone Distinguish Healthy Controls from Radiologically Isolated Syndrome Subjects? (ID 238)

Speakers
Presentation Number
P0034
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Radiologically isolated syndrome (RIS) is defined by the incidental finding of MRI lesions suggestive of multiple sclerosis in subjects with a normal neurological examination. Some studies suggested that the use of wearables could unveil infra-clinical differences between RIS subjects and healthy controls (HC).

Objectives

To demonstrate that digital biomarkers collected by a smartphone application can distinguish healthy controls (HC) from subjects with radiologically isolated syndrome (RIS).

Methods

We created a mobile app called MS Screen Test (MSST) that contains:

- Finger tapping speed test: during this task, we measure the mean tapping speed for the dominant hand and the non dominant hand

- Level test: the subject is asked to tilt the phone to move a ball inside a target, then maintain it inside the target for 10 seconds. We measure the required time to bring the ball to the target, then the proportion of time during which the ball is maintained inside the target

- Low contrast vision (LCV) test: letters with varying contrast randomly appearing on the screen. The subject has to tap on the screen each time a letter is seen. The number of good answers is collected

- Cognition test: letters or digits randomly appear on the screen. The subject has to tap on the screen only if a letter is seen. The mean tap latency in milliseconds is collected as well as bad answers

A cohort of HC and RIS subjects were evaluated to compare performances on MSST.

Results

60 HC and 16 RIS subjects were prospectively included (F/M 3.15, mean age 41.6 yrs)

Compared to HC, RIS subjects had a lower tapping speed on both dominant (5.6 Hz vs 6.5 Hz, p=0.001) and non dominant hand (5.1 Hz vs 5.6 Hz, p=0.04), fewer detected letters on the LCV test (10 vs 13, p=0.001) and a higher latency of response on the cognitive test (731 ms vs 599 ms, p<0.0001).

On the level test, the time during which the ball was maintained is the target was shorter for RIS subjects (3 sec vs 4.9 sec, p=0.05).

Conclusions

Our study confirms that digital biomarkers collected by a smartphone can unveil differences between HC and subjects at a presymptomatic stage of MS.

It would be relevant to evaluate whether those biomarkers could predict the risk of conversion to multiple sclerosis, as well as to evaluate their potential predictive value in early diagnosed MS patients

Collapse
Clinical Trials Poster Presentation

P0193 - BEST-MS: A standardized and prospective study comparing the efficacy of natalizumab versus fingolimod in active relapsing multiple sclerosis (ID 237)

Abstract

Background

Therapeutic options are growing for active RRMS patients, however, few prospective studies are available to compare the efficacy of those treatments. Best Escalation Strategy in MS (BEST MS) started in France in 2013 when natalizumab (NTZ) and fingolimod (FTY) were the two most employed second-line therapies in active RRMS.

Objectives

To compare the efficacy between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting multiple sclerosis (RRMS).

Methods

BEST-MS is a French prospective multicentric study.

Patients with active RRMS (defined as at least 1 relapse in the last 12 months on a well-conducted 1st line treatment with at least 9 T2 hyperintensities on MRI, OR at least 2 relapses in the last 12 months with evidence of active disease on MRI for naïve patients) were enrolled to be treated either with NTZ or FTY. Treatments choice was at the discretion of the physician.

Relapses, EDSS and brain MRI were collected at baseline and at 12 months.

The main outcome measure was the proportion of patients reaching No Evidence of Disease Activity (NEDA) at 12 months, defined as the absence of relapses, absence of new T2 lesions, absence of new gadolinium enhancing lesions and a stable EDSS score.

Results

230 patients were included (age: 38.2 yrs, F/M: 3.1, FTY: 117, NTZ: 113). There was no statistical difference between groups regarding baseline characteristics.

Treatment drop out rate was higher in FTY group (22% vs 12%, p<0.0001) and most of thoses cases were related to a lack of efficacy.

At M12, 43% of patients treated with NTZ reached NEDA versus 27% in the FTY group (p=0.04)

NTZ indicated a better efficacy regarding new T2 lesions (0.7 vs 1.4, p=0.01) and gadolinium enhancing lesions (0.03 vs 0.5, p<0.0001).

Relapse rate (ARR) was lower in NTZ group (0.2 vs 0.27, p = 0.04), even if most relapses occurred during the first 4 months of treatment in both groups.

Conclusions

NTZ showed higher efficacy than FTY on MRI in active RRMS patients. ARR was also lower in favor of NTZ, but most relapses occurred early. However, the rate of drop out was higher for patients treated with FTY.

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