Medical University of Innsbruck
Neurology

Author Of 5 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0126 - Olfactory threshold as a biomarker predicting treatment response in relapsing multiple sclerosis (ID 296)

Speakers
Presentation Number
P0126
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Olfactory threshold impairment is transiently occurring in patients with active multiple sclerosis (MS) and during acute MS relapse resolving in phases of clinical stability and after initiation of disease-modifying treatment (DMT). Thus, threshold impairment is a marker of short-term inflammatory activity in relapsing multiple sclerosis (RMS).

Objectives

The objective of this study was to investigate the potential of olfactory threshold for prediction of treatment response in RMS.

Methods

In this 4-year prospective observational study on 113 RMS patients, olfactory threshold was measured at DMT initiation (M0) and after 3 (M3) and 12 months (M12) of follow-up by the Sniffin’ Sticks test. Inclusion criteria included adherence to DMT for at least 2 years. Treatment response was defined as absence of relapse during the observation period. Best possible cut-off values of olfactory threshold for predicting treatment response were determined by receiver-operating characteristics (ROC) analyses. Odds ratios (OR) for treatment response were calculated by stepwise multivariate logistic regression models correcting for age, sex, and disease duration at baseline.

Results

A combination of threshold score ≥6.0 at M3 and ≥1.0 points improvement from M0 to M3 sustained to M12 displayed the best prediction of treatment response (OR 5.1; 95% CI: 2.3 – 7.8; p<0.001; specificity 90%, sensitivity 83%) followed by threshold score ≥6.0 at M3 alone (OR 3.6; 95% CI: 1.3 – 7.0; p<0.001; specificity 83%, sensitivity 76%), ≥1.0 points improvement from M0 to M3 sustained to M12 alone (OR 3.5; 95% CI: 1.2 – 6.8; p<0.001; specificity 82%, sensitivity 70%). Threshold score at M12 alone and improvement from M3 to M12 was not significantly predictive. Also, adding threshold score at M12 to the model did not improve predictive accuracy.

Conclusions

Olfactory threshold impairment predicts relapse activity upon DMT initiation. Pending validation, olfactory threshold may be a useful and easily obtainable biomarker of treatment response in RMS.

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Biomarkers and Bioinformatics Poster Presentation

P0148 - Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis (ID 304)

Speakers
Presentation Number
P0148
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Retinal thinning is a biomarker of neuroaxonal degeneration in multiple sclerosis (MS) and is associated with disability progression. Recently, the term PIRA, or progression independent of relapse, has emerged purporting to quantify the proportion of disability worsening due to non-inflammatory neurodegenerative processes.

Objectives

The objective of this study was to determine the association of retinal thinning with PIRA in comparison to traditional physical disability worsening and relapse.

Methods

In a 4-year prospective observational study including 171 relapsing MS (RMS) patients, retinal thinning was determined by annual spectral-domain optical coherence tomography measuring macular-ganglion-cell-and-inner-plexiform-layer(mGCIPL). Physical disability was assessed by expanded disability status scale (EDSS), cognitive disability by the symbol digit modalities test (SDMT). PIRA was defined as either an EDSS or SDMT worsening during the observation period confirmed after 24 weeks with no relapse in the 30 days before or after the disability worsening. Multivariate linear regression models adjusted for sex, age, disease duration and disease-modifying treatment regarding retinal thinning were calculated.

Results

Each PIRA event was associated with a mean additional loss of GCIPL (1.8µm) and pRNFL (1.9µm), similar to the impact of EDSS and SDMT worsening. Overall relapse and relapse without subsequent EDSS worsening did not influence retinal thinning, while a relapse with EDSS worsening was associated with an additional loss of GCIPL (1.3µm) and pRNFL (1.4µm).

Conclusions

PIRA is associated with retinal thinning, likely reflecting non-inflammatory neurodegenerative processes. It might be a clinical measure to identify MS patients with ongoing MS-associated neurodegeneration.

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Biomarkers and Bioinformatics Poster Presentation

P0149 - Retinal layer thinning rate as a biomarker predicting treatment response in relapsing multiple sclerosis (ID 295)

Speakers
Presentation Number
P0149
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell plus inner plexiform layer (mGCIPL) thinning are markers of neuroaxonal degeneration in relapsing multiple sclerosis (RMS). pRNFL and mGCIPL thinning is more pronounced in patients with physical or cognitive disability progression, while it is reduced by disease-modifying treatment (DMT).

Objectives

The objective of this study was to investigate the potential of retinal layer thinning for prediction of treatment response in RMS.

Methods

In this 4-year prospective observational study on 113 RMS patients, pRNFL and GCIPL were measured at DMT initiation and after 12 (M12) and 24 months (M24) of follow-up by spectral-domain optical coherence tomography (OCT). Inclusion criteria included adherence to DMT for at least 2 years. Patients suffering optic neuritis between baseline and M24 were excluded. Treatment response was defined as absence of 6 month confirmed EDSS progression and Symbol Digit Modalities Test (SDMT) worsening during the observation period. Best possible cut-off values of retinal thinning for predicting treatment response were determined by receiver-operating characteristics (ROC) analyses. Odds ratios (OR) for treatment response were calculated by multivariate logistic regression models correcting for age, sex, disease duration and EDSS/SDMT at baseline.

Results

Thinning of mGCIPL <0.5mm at M24 displayed superior prediction of treatment response (odds ratio [OR] 4.5; 95% confidence interval [CI]: 1.8 – 7.6; p<0.001; specificity 91%, sensitivity 81%) followed by mGCIPL <0.3mm at M12 (OR 3.9; 95% CI: 1.4 – 6.9; p<0.001; specificity 85%, sensitivity 78%) and pRNFL <2mm at M24 (OR 3.7; 95% CI: 1.1 – 6.5; p=0.023; specificity 84%, sensitivity 69%), while pRNFL at M12 was not significantly predictive.

Conclusions

mGCIPL – and to a lesser degree pRNFL – thinning predict physical and cognitive disability progression upon DMT initiation. Pending validation, retinal layer thinning may be a useful and easily accessible biomarker of treatment response in RMS.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0347 - Late-onset neutropenia in a multiple sclerosis patient after first dose ocrelizumab switched from rituximab (ID 127)

Speakers
Presentation Number
P0347
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Ocrelizumab is a humanized monoclonal anti-CD20 antibody approved for treatment of relapsing-remitting and primary progressive multiple sclerosis (MS). Before approval of this drug, the chimeric anti-CD20 antibody rituximab was used off-label for treatment of MS. On treatment with rituximab late-onset neutropenia (LON) was reported as a rare adverse event primarily in rheumatologic patients.

Objectives

So far, only two patients developing LON on treatment with ocrelizumab were reported leaving open the question about potential underlying mechanisms. By reporting a case of LON in a patient treated first with rituximab followed by ocrelizumab, we aim to raise awareness to this rare, but potentially threatening adverse event.

Methods

Here we report the case of a 21 years old female caucasian patient with highly active relapsing-remitting multiple sclerosis, who experienced LON after first dose ocrelizumab switched from rituximab.

Results

Our patient was first treated with two cycles rituximab in a dosage of 375 mg/m² body surface due to highly active multiple sclerosis. On treatment with rituximab she did not show any hematologic abnormalities. After interruption of treatment due to pregnancy she was switched to ocrelizumab and developed grade IV LON with neutrophil counts as low as 0.1x109/L.

Conclusions

This first case of LON in a patient treated with different anti-CD20 antibodies highlights the necessity of regular hemogram examinations on treatment with ocrelizumab. Patients may develop LON during ocrelizumab even if rituximab was previously well tolerated.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0375 - Quantifying the risk of disease reactivation after DMT discontinuation – the VIAADISC score (ID 765)

Abstract

Background

There is a lack of evidence guiding treatment decisions regarding discontinuation of disease-modifying therapy (DMT) in multiple sclerosis (MS)

Objectives

To generate and validate a composite (clinical and MRI-based) score able to identify individual patients with relapsing MS (RMS) with a high risk of experiencing disease reactivation after discontinuation of DMT.

Methods

The study was conducted using a generation and a validation dataset drawn from two separate prospectively collected observational databases. We included RMS patients who received interferon-beta or glatirameracetate for ≥12 months, then discontinued DMT for ≥6 months and had ≥2 years of follow-up available. In the generation sample (n=168), regression analysis was performed to identify clinical or MRI variables independently predicting disease reactivation after DMT discontinuation. A predictive score was calculated using the variables included in the multivariable model. This score was then applied to the validation sample (n=98).

Results

The variables included in the final model as independent predictors of disease reactivation were age at discontinuation (p<0.001), MRI activity at discontinuation (p<0.001), and duration of clinical stability (p<0.001). The resulting score (Vienna Innsbruck DMT discontinuation score based on age, activity on MRI and duration in stable course; VIAADISC) was able to identify patients at high (83-84%), moderate (35-38%) and low risk (7%) of disease reactivation within 5 years after DMT discontinuation both in the generation and in the validation cohorts.

Conclusions

The composite VIAADISC score may be a valuable tool informing patients and neurologists in the face of deciding if and when to discontinue injectable DMTs.

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