Monash University
Department of Neuroscience, Central Clinical School

Author Of 1 Presentation

Gender Differences, Hormones and Sex Chromosomes Oral Presentation

PS12.04 - Pregnancy in a modern day multiple sclerosis cohort: Predictors of relapse during pregnancy

Abstract

Background

Historically, disease activity diminished during pregnancy in women with relapsing-remitting MS. Today, women with high disease activity are more likely to attempt pregnancy due to the disease control that new therapies offer. But disease activity during pregnancy in the modern day remains understudied.

Objectives

Describe disease activity in a modern pregnancy cohort, grouped by preconception disease-modifying therapy (DMT) class; determine the predictors of relapse during pregnancy.

Methods

Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included. DMT were classed by low, moderate and high-efficacy. Annualized relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of relapse during pregnancy were determined using clustered logistic regression.

Results

We included 1640 pregnancies from 1452 women. DMT used in the year before conception were none (n=346), low (n=845), moderate (n=207) and high-efficacy (n=242). Most common DMT in each class was interferon-beta (n=597), fingolimod (n=147) and natalizumab (n=219) for low, moderate and high-efficacy respectively. Conception EDSS ≥2 was more common in higher efficacy DMT groups (high: 41.3%; moderate 28.5%; low 22.4%; none 20.2%). For low-efficacy and no DMT groups, ARR fell through pregnancy. ARR of the moderate-efficacy group increased in the 1st pregnancy trimester (0.55 [95% CI 0.36-0.80] vs 0.14 [95% CI 0.10-0.21] on low-efficacy), then decreased to a trough in the third. Conversely, ARR steadily increased throughout pregnancy for those on high-efficacy DMT (3rd trimester: 0.42 [95% CI 0.25-0.66] vs 0.12 [95% CI 0.07-0.19] on low-efficacy). Higher efficacy DMT groups were associated with higher ARR in the early postpartum period (high: 0.84 [95% CI 0.62-1.1]; moderate: 0.90 [95% CI 0.65-1.2]; low: 0.47 [95% CI 0.38-0.58]). Preconception use of high and moderate-efficacy DMT and higher preconception ARR were predictors of relapse in pregnancy. But, continuation of high-efficacy DMT into pregnancy was protective against relapse (odds ratio 0.80 [95% CI 0.68-0.94]). Age ≥35 years was associated with reduced odds of relapse.

Conclusions

Women with RRMS treated with moderate or high-efficacy DMT are at greater risk of relapse during pregnancy. Careful pregnancy management, and use of long-acting high-efficacy DMT preconception, or continuing natalizumab into pregnancy, may prevent relapse in pregnancy.

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Author Of 3 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0121 - Objective measurement of speech correlates with disease status and quality of life in people with MS without dysarthria (ID 1681)

Speakers
Presentation Number
P0121
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Objective measurement of speech has shown promising results to monitor disease state in Multiple Sclerosis (MS). Yet, it is not clear if changes in speech can be detected before overt dysarthria.

Objectives

In this study, we characterize the relationship between disease severity and objective speech metrics exclusively in people with no perceivable dysarthria.

Methods

An acoustic composite score was calculated using regression modelling of speech data from 119 people with MS (pwMS, 75% female), irrespective of dysarthria presence. That score was then tested in pwMS without dysarthria, as determined by blinded perceptual rating, for correlations with the Expanded Disability Status Scale (EDSS), brain volume and lesion load from magnetic resonance imaging, and quality of life scores from the Multiple Sclerosis Impact Scale (MSIS-29) .

Results

PwMS without dysarthria (n=77) were more likely to be female (82% vs 62%, p=0.017), were on average 5.7 years younger (age mean ± standard deviation 53.5±11.4, p=0.009), had MS for 2.5 years shorter (11±8.5 years, p=0.034) and scored EDSS 1.7 step lower (2.7±1.9, p<0.001) than pwMS with dysarthria (n=42). The acoustic composite score correlated with EDSS scores (r=0.45, p<0.001) and quality of life (r=0.4, p=0.01) in pwMS without perceivable dysarthria, but not with brain volume or lesion load.

Conclusions

Acoustic analysis offers a valuable insight into the subclinical development of speech impairment in MS. These results highlight the potential of automated analysis of speech to assist in monitoring disease progression and treatment response.

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Neuropsychology and Cognition Poster Presentation

P0831 - Validation of longitudinal reaction time trajectories in multiple sclerosis using the MSReactor computerized battery and latent class analysis. (ID 1660)

Speakers
Presentation Number
P0831
Presentation Topic
Neuropsychology and Cognition

Abstract

Background

Longitudinal cognitive trajectories in MS are heterogenous and difficult to measure. Computerised tests designed to screen broad cognitive domains may be a reliable method to detect discrete trajectories of cognitive performance

Objectives

To validate a latent class model to identify trajectories of reaction time change in people with relapsing remitting MS (pwRRMS).

Methods

The MSReactor computerised cognitive battery is a self-administered, online set of reaction time tasks assessing psychomotor function (PsychoM), visual attention (VisAtt) and working memory (WorkingM). Participants completed both 6-monthly in-clinic testing and additional remote testing. Latent class analysis was used to model the longitudinal reaction times and identify discrete cognitive trajectories within the heterogeneous data. We applied a cross validation method to confirm the optimal models for all three reaction time tasks. Briefly, the cohort was split into training and test sets (50:50) and the mean root mean square error (RMSE) calculated for the difference between training and test trajectories calculated at each day of follow up, over 100 repetitions. To determine the minimum number of tests required to reliably classify an individual into a longitudinal trajectory the dataset for each task was reduced to 3, 4 and 5 tests per participant and classification compared to the complete dataset.

Results

We included 478 pwRRMS who had completed at least 3 MSReactor tests over a minimum of 30 days follow up. In total, 3846 individual tests were included in each model (median tests/participant=5 (range 3-332), mean follow up of 774 +- 359.5 days). Three latent classes were identified for each task, with the PsychoM task identifying a group of pwRRMS with a mean predicted trajectory of slowing reaction times. In validation, the PsychoM task was the most consistent with the smallest RMSE for each of the 3 classes (68 milliseconds (ms), 95%CI 59-77ms; 61ms, 95% CI 50-72ms and 16ms, 95% CI 14-18ms) followed by the VisAtt task (RMSE = 114ms, 95ms and 29ms) and WorkingM task (RMSE = 137ms, 138ms and 46ms). Reduced datasets of 3, 4 and 5 tests per participant in the PsychoM task were able to classify participants into the trajectories identified in the full dataset model, with 83%, 86% and 90% accuracy respectively.

Conclusions

Latent class modelling of longitudinal reaction times collected with MSReactor was able to detect discrete trajectories of cognitive performance. The PsychoM task latent class model identified a group of RRMS with a mean predicted slowing of reaction times and was the most consistent model in cross validation. Performing the modelling on just 3, 4 or 5 tests per participant was highly accurate in defining latent trajectories, giving the battery clinical utility where multiple years of follow up may not be realistic.

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Reproductive Aspects and Pregnancy Poster Presentation

P1131 - Pregnancy in a modern day multiple sclerosis cohort: Predictors of postpartum relapse and disability progression (ID 1321)

Abstract

Background

Disease activity has been investigated in pregnant women with RRMS treated with low-efficacy or no therapy. How newer, more efficacious therapies affect relapse and disability progression risk after pregnancy remains understudied.

Objectives

To describe disease activity in a modern pregnancy cohort contrasted with historical cohorts. To determine the predictors of postpartum relapse and the predictors of six-month confirmed disability progression events in a contemporary pregnancy cohort.

Methods

Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 (modern cohort) were compared with those conceived between 2005-2010 and pre-2005. Annualised relapse rates (ARR) were calculated for each pregnancy trimester and 12 months either side. Predictors of time-to-relapse postpartum (1st 3 months) and time to 6-month confirmed disability progression event were determined with clustered Cox regression analyses. Breastfeeding duration and time to DMT reinitiation were modelled as time-varying covariates.

Results

We included 1640 pregnancies from 1452 women (modern cohort). Disease-modifying therapy (DMT) used in the year before conception included interferon-beta (n=597), natalizumab (n=219) and fingolimod (n=147). Continuation of DMT up to conception increased over time (31% pre-2005 vs 54% modern cohort). Preconception ARR decreased across epochs (pre-2005: 0·58 [95% CI 0·49-0·70]; 2005-2010: 0·40 [95% CI 0·36-0·45]; modern: 0·29 [95% CI 0·27-0·32]). In all epochs, ARR decreased during pregnancy to reach similar troughs in the 3rd trimester, and rebounded in the 1st 3-months postpartum. Preconception use of high-efficacy DMT predicted early postpartum relapse (hazard ratio (HR) 2.1 [1.4-3.1]); although those on no DMT were also at risk of postpartum relapse, relative to women on low-efficacy DMT (HR 2.7 [1.2-5.9]). Conception EDSS 2, higher preconception and in-pregnancy ARR were also risk factors. DMT reinitiation, particularly of high-efficacy DMT (HR 0.17 [0.07-0.38]), was protective against postpartum relapse. Women who breastfed were less likely to relapse (HR 0.63 [0.42-0.94]). 4.5% of modern pregnancies had confirmed disability progression after delivery. This was predicted by higher pregnancy and postpartum ARR, with postpartum ARR remaining independently predictive in multivariable analysis (HR 1.5 [1.2-2.0]).

Conclusions

The early postpartum period remains a period of vulnerability for disease rebound in women with MS in the modern era. Early DMT reinitiation, particularly with high-efficacy treatment, is protective against postpartum relapse. Confirmed disability progression events after pregnnacy are uncommon in the modern era. Relapse activity is the key driver of these events.

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