Author Of 6 Presentations
P0126 - Olfactory threshold as a biomarker predicting treatment response in relapsing multiple sclerosis (ID 296)
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.
P0148 - Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis (ID 304)
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.
P0149 - Retinal layer thinning rate as a biomarker predicting treatment response in relapsing multiple sclerosis (ID 295)
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.
P0347 - Late-onset neutropenia in a multiple sclerosis patient after first dose ocrelizumab switched from rituximab (ID 127)
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.
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.
P1054 - Sexual dysfunction in multiple sclerosis: who is at risk? (ID 1793)
Abstract
Background
Multiple sclerosis (MS) related disability and sexual dysfunction (SD) are known to lower a patient’s health related quality of life (HRQoL) detrimentally. However, taking a sexual history in routine care is commonly evaded. Furthermore, there is not much knowledge on SD being either an independent symptom or merely a byproduct of other symptoms such as depression or anxiety.
Objectives
To investigate the prevalence of SD in patients with MS and unveil possible associations with disease parameters, depression, anxiety and HRQoL.
Methods
We present results from a cross-sectional study of 93 patients with MS. SD was determined based on the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and correlated with physical disability (Expanded disability status scale, EDSS), depression and anxiety (Hospital Anxiety and Depression Scale, HADS), and HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire, MSQoL-54).We present results from a cross-sectional study of 93 patients with MS. SD was determined based on the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) and correlated with physical disability (Expanded disability status scale, EDSS), depression and anxiety (Hospital Anxiety and Depression Scale, HADS), and HRQoL (Multiple Sclerosis Quality of Life-54 questionnaire, MSQoL-54).
Results
The mean (standard deviation) age in our cohort was 39 (11.4) years and sex distribution was 3:2 (f:m). At the time of enrollment, two thirds of patients had relapsing MS. The median (IQR) EDSS was 2.0 (0-4.5) with one third of patients being rated as 4.0 or higher. SD was reported by 43 (46%) patients on the MSISQ-19. Out of all included patients, 32 (34%) suffered from anxiety and 15 (16%) from depression. In comparison of patients with and without SD, we found that patients affected by SD were significantly more likely to be depressed (28% vs. 6%, p=0.005) and had a higher median [IQR] EDSS (1 [1-3] vs. 4 [1.5-6], p<0.001). HRQoL was significantly poorer in patients with MS suffering from SD (median [IQR] MSQoL-54 scores: physical subscale 52 [41-68] vs. 81 [69-89], p<0.001; mental subscale 50 [38-82] vs. 86 [70-89], p<0.001). Furthermore, SD occurred more frequently in the progressive phase of the disease. We found no associations between sexual functioning and age, sex or MS disease duration. In a multivariate linear regression model, we found the risk for SD to be 18.1-fold higher (95%CI 3.3-31.4, p<0.001) in patients with EDSS≥4, while neither depression nor anxiety were independent predictors of SD.
Conclusions
SD is common among people with MS and should be addressed in clinical routine. The risk for SD is growing substantially with increasing EDSS while being independent of depression and anxiety. SD is clearly associated with poorer HRQoL. Nonetheless, guidelines for a structured approach, patient needs and treatment strategies should be investigated further.
Presenter Of 4 Presentations
P0126 - Olfactory threshold as a biomarker predicting treatment response in relapsing multiple sclerosis (ID 296)
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.
P0148 - Retinal layer thinning is reflecting disability progression independent of relapse activity in multiple sclerosis (ID 304)
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.
P0149 - Retinal layer thinning rate as a biomarker predicting treatment response in relapsing multiple sclerosis (ID 295)
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.
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.