Cleveland Clinic
Lou Ruvo Center for Brain Health

Author Of 6 Presentations

COVID-19 Late Breaking Abstracts

LB1251 - National Multiple Sclerosis Society Healthcare Provider Councils COVID-19 Survey (ID 2138)

Speakers
Presentation Number
LB1251
Presentation Topic
COVID-19

Abstract

Background

The COVID-19 crisis has created unanticipated changes in health care delivery for people living with multiple sclerosis (MS). The pandemic’s rapid evolution has resulted in a knowledge gap about how COVID-19 has affected practice patterns of MS clinicians.

Objectives

To understand how the COVID-19 pandemic has affected clinical practice patterns of a nationwide cohort of MS clinicians across the United States.

Methods

In collaboration with the National Multiple Sclerosis Society (NMSS), we used SurveyMonkeyTM to develop a 28-item electronic questionnaire exploring MS specialists’ perceptions of how COVID-19 has altered how they prescribe MS disease-modifying therapies (DMTs) and provide telehealth and other services, and issues affecting their own well-being including re-deployment to the front lines of COVID-19 care and availability of personal protective equipment. NMSS staff sent a recruitment email containing the electronic survey link to 188 clinicians who serve on regional NMSS Healthcare Provider Councils across the United States, 86 of whom were MS specialist physicians.

Results

Eighty-six respondents (46% of 188 clinicians) from 32 U.S. states completed the survey including 45 physicians, 18 rehabilitation therapists, 7 psychologists, 6 advanced practice clinicians, 4 social workers, 2 nurses, a pharmacist and a researcher. More than 72% of all respondents believed they have adequate personal protective equipment at work, while only 37.2% indicated they could safely distance themselves from others at work. Nearly 6% of respondents reported they had been re-deployed to the front lines of COVID-19 patient care, and an additional 15% anticipated being re-deployed. The physician subgroup had a 54% response rate and included 41 neurologists, 3 physiatrists and 1 family physician. More than one-third of physicians indicated that since the pandemic began, they use telemedicine to provide more than 75% of their clinical care. Nearly 80% believed COVID-19 may have changed how they prescribe DMTs. DMTs prescribed more often during the pandemic included β-interferons (28.6% of 42 prescribers), natalizumab (25%) and glatiramer acetate (21.4%), while DMTs prescribed less often included alemtuzumab (64.2%), cladribine (52.4%), and B cell-depleting agents including ocrelizumab and rituximab (50%). Some MS specialists reported suspending certain DMTs during the pandemic (21.4% each for alemtuzumab and B cell-depleting agents) and/or extending the dosing intervals (38.1% for natalizumab and 11.9% for fingolimod and siponimod).

Conclusions

In this nationwide survey, MS specialist physicians and other clinicians serving on regional NMSS Healthcare Provider Councils across the U.S. reported major changes in their delivery of MS care during the COVID-19 pandemic. Further research is warranted to explore these trends and to develop consensus guidelines on best treatment practices for patients living with MS.

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Clinical Outcome Measures Poster Presentation

P0142 - Real-world effectiveness of dimethyl fumarate versus fingolimod using novel outcomes in a heterogeneous patient cohort (ID 708)

Speakers
Presentation Number
P0142
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Prior studies suggested comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapses and traditional MRI metrics. We expanded on these assessments with new outcomes, while also accounting for comorbidities.

Objectives

Compare the real-world effectiveness of DMF vs. FTY with standardized neuroperformance, MRI, and biomarker (serum neurofilament light [sNfL]) measures.

Methods

Patients were eligible if on DMF or FTY at enrollment in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network with ≥1 year of follow up and ≥1 MRI in the previous year. Sensitivity analysis included a sub-group of patients who initiated DMF or FTY within 2 years prior to MS PATHS. Propensity score weighting model covariates included demographics, MS disease history parameters, clinical and radiographic characteristics, cardiovascular disease, and diabetes. Generalized estimating equation (GEE) models assessed the differences in means and in 1-year change in neuroperformance and MRI outcomes. Logistic regression models compared sNfL with age-adjusted normative thresholds.

Results

644 DMF and 564 FTY patients had neuroperformance data, 194-354 DMF and 201-385 FTY patients had MRI assessments, 152 DMF and 118 FTY patients had NfL samples. The number of follow-up assessments was comparable between groups (approximately 2 clinical, 2 MRI, and 1 biomarker). Mean time (SD) since treatment initiation was 2.2 (1.5) years for DMF and 2.6 (2.1) years for FTY. No differences were observed in the means or slopes of change for any of the analyzed outcomes. Differences in slopes of change were minimal for processing speed (0.06, p=0.8), manual dexterity (-0.1, p=0.5), walking speed (-0.03, p=0.7), contrast sensitivity (-0.03, p=0.9), patient-determined disease steps (0.02, p=0.5), relapses (0.001, p=0.9), brain parenchymal fraction (0.0003, p=0.3), new T2 lesions (0.3, p=0.1), Gd+ lesions (0.1, p=0.1), and grey matter fraction (0.002, p=0.2). There was no difference in the proportion of patients with elevated sNfL (p=0.12). The sub-group consisted of 123 DMF and 130 FTY patients with mean time (SD) since treatment initiation of 10.2 (6.9) and 10.9 (7.2) months, respectively. Subgroup sensitivity analyses showed similar findings.

Conclusions

DMF and FTY demonstrated similar effectiveness on standardized quantitative neuroperformance, MRI, and biomarker outcomes in a heterogeneous, real-world cohort.

Supported by: Biogen

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Disease Modifying Therapies – Risk Management Poster Presentation

P0409 - Treatment Failure in patients with multiple sclerosis initiating frequently used first line therapies (ID 885)

Speakers
Presentation Number
P0409
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Despite an array of disease modifying therapies (DMTs), interferons/glatiramer acetate (IFN/GA) and dimethyl fumarate (DMF) are still the most frequently used to treat multiple sclerosis (MS) in United States.

Objectives

Our objective was to evaluate treatment patterns and disease breakthrough for patients initiating IFN/GA/DMF as first-line therapies to determine if there is an unmet need for more effective agents to be used first-line.

Methods

Adult MS patients (age ≥18) with ≥1 DMT claims of IFN/GA/DMF from January 2016-March 2018 were identified using a large US administrative claims database (IBM® MarketScan® Database). The date of the first MS DMT claim was defined as the index date and patients were followed for one year. Treatment switch was defined as changing from initial therapy to another DMT (within 60 days) and discontinuation was defined as no DMT use for at least 60 days after stopping the initial DMT. Breakthrough-disease was defined as occurrence of relapse (characterized via a validated claims algorithm) during the treatment period. Outcomes were evaluated as a combined DMT group and by individual DMTs.

Results

We identified 1,096 patients initiating IFN/GA and 565 patients initiating DMF. Of these, 43.4% experienced treatment failure (29.3% discontinued or 14.1% switched DMTs) within one year of initiation (results for individual DMTs were similar). The median time to discontinuation was 4.8 months, and the median time to switch was 5.6 months. Approximately, 28.2% of patients experienced at least 1 relapse over the 1-year observation period. The median time to relapse was 4.6 months. There was no reduction in annualized relapse rate (ARR) after initiation of IFN/GA/DMF therapy [ARR for 1-year prior to initiation = (0.41) and 1 year post-initiation = (0.42)].

Conclusions

There is an unmet need for early use of high efficacy DMT, as the most frequently used first-line DMTs show treatment failure (discontinuation/switching/disease-breakthrough) and lack of treatment benefit at high rates in a real-world setting.

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Observational Studies Poster Presentation

P0843 - Characteristics and clinical outcomes of older patients with MS treated with peginterferon beta-1a or intramuscular interferon beta-1a in MS PATHS (ID 792)

Speakers
Presentation Number
P0843
Presentation Topic
Observational Studies

Abstract

Background

Safety and effectiveness information for peginterferon beta-1a or intramuscular interferon (IM IFN) beta-1a in older patients (≥60 years [y]) with multiple sclerosis (MS) are limited. MS PATHS, an international network of MS centers, provides access to real-world (RW) data generated from a broad MS patient population.

Objectives

Evaluate the clinical outcomes of patients ≥60 y of age in MS PATHS treated with peginterferon beta-1a or IM IFN beta-1a.

Methods

Included patients were currently taking peginterferon beta-1a or IM IFN beta-1a or began taking either therapy at a follow-up visit, and had ≥1 follow-up clinical assessment as of November 2019. Assessments included Patient-Determined Disease Steps (PDDS), and Multiple Sclerosis Performance Test (MSPT) assessments, including Processing Speed Test (PST), Manual Dexterity Test (MDT), and Walking Speed Test (WST). Z-scores were based on normative data from 500 healthy volunteers.

Results

Analysis included 817 patients, of whom 218 (27%) were aged ≥60 y at baseline (BL). Follow-up times were similar for ≥60 y and <60 y patients (mean [SD] 1.35 [0.97] y and 1.27 [0.94] y, respectively). Older patients had higher BL PDDS score (mean [SD] 1.82 [2.14] vs 0.91 [1.48]) and higher rates of comorbidities including pain, cardiovascular, and dyslipidemia than younger patients. At BL, patients ≥60 y had significantly greater functional impairment than patients <60 y on MDT (Z-score mean [SD] -0.85 [1.79] vs -0.23 [1.56]) and WST (-1.66 [3.35] vs -0.52 [2.30]; both P<0.001), but not PST (-0.48 [1.00] vs. -0.37 [1.11]; P=0.197). Change from BL in PST, MDT or WST Z-scores at 6 months (mo), 1 y or 2 y was not significant for patients ≥60 y, whereas those <60 y showed significant improvement in PST at all 3 time points (mean change in Z-score 0.11–0.26; all P≤0.006) and in MDT at 1 and 2 y (mean change in Z-score 0.24 and 0.36; both P≤0.003). Approximately half of the ≥60-y and <60-y subgroups were relapse free at 6 mo (57% and 58%), 1 y (48% and 61%) and 2 y (49% and 60%).

Conclusions

In this RW study of patients with MS aged ≥60 or <60 y treated with peginterferon beta-1a or IM IFN beta-1a, younger patients had significantly improved PST and MDT ≥6 mo post-BL, and approximately equal proportions of patients in both age groups were relapse-free over 2 y. These results indicate that peginterferon beta-1a and IM IFN beta-1a may provide RW treatment benefits to patients with MS, including those aged 60 and above.

This study was supported by Biogen.

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Observational Studies Poster Presentation

P0885 - MSProDiscussTM is a useful tool to aid discussion of multiple sclerosis disease progression: Results from a large, real-world qualitative survey (ID 1177)

Abstract

Background

MSProDiscussTM is a validated, physician-completed tool aimed at facilitating physician–patient conversation on signs of progression in multiple sclerosis (MS). A set of weighted questions on relapses, symptoms and their impacts as experienced by the patient generate a traffic light system output to aid the discussion. The tool is available online at www.msprodiscuss.com.

Objectives

Evaluate the usability and usefulness of MSProDiscuss in discussing disease progression in daily clinical practice.

Methods

An online qualitative survey consisting of individual questionnaires completed by healthcare professionals (HCPs) after using MSProDiscuss in patient consultations and a final questionnaire to capture overall experience on the tool was conducted in 34 countries. General feedback and recommendations for improving the tool were also collected.

Results

In total, 301 HCPs participated in the survey. The HCPs first completed individual questionnaires after using MSProDiscuss on 6974 MS patients and then a final questionnaire. In 97% (initial questionnaire, i) and 98% (final questionnaire, f) of the time MSProDiscuss was used, the time taken to complete the tool was considered satisfactory (1-4min). The questions were found to be comprehensible in 94% (i) to 97% (f) of cases, and HCPs are willing to use the tool again in the same patient 91% (i) of the time. MSProDiscuss was also useful in discussing MS symptoms and its impact on daily activities (88% i / 92% f) and cognitive function (79% both i and f) and in discussing progression in general (88% i / 90% f).

Moreover, in the final questionnaire, 95% agreed that the questions were similar to those asked by a HCP in a regular consultation. MSProDiscuss was also found to be helpful for understanding the impact of MS symptoms on daily activities (91%) and cognitive function (80%). Overall, 92% of the HCPs would recommend MSProDiscuss to a colleague; 92% think that it is feasible and 86% are willing to integrate MSProDiscuss into their clinical practice. Key recommendations were to allow for longitudinal follow-up, expand on cognitive assessments, and provide a patient-completed version. These have been considered for implementation in the updated version of MSProDiscuss.

Conclusions

The survey results established MSProDiscuss as useful and easy to use tool to facilitate patient-physician discussion of MS progression by structured capturing of patient clinical profile. Most HCPs were willing to integrate MSProDiscuss into their daily clinical practice.

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1036 - Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: results from MS PATHS (ID 1794)

Speakers
Presentation Number
P1036
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Understanding patient-reported changes in physical, mental, and social health after starting MS therapy is important in optimizing treatment.

Objectives

Assess changes in the Quality of Life in Neurological Disorders (Neuro-QoL; NQ) questionnaire after starting natalizumab (NAT) and compare to another high efficacy therapy - ocrelizumab (OCR).

Methods

T-scores of 12 NQ domains were obtained at routine visits in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network. NQ scores from visits post NAT initiation were compared to last previous NQ (baseline, BL) to calculate the annualized rate of change and the likelihood of clinically meaningful change (≥5-point) in the overall cohort and in patients with abnormal BL NQ (T-score worse than 50; 36%-76% of the population). Subgroup analyses in NAT- and OCR-treated patients were conducted with multivariate mixed-effects regression models after propensity score weighting and adjustment for antidepressants, year and drug*year interaction.

Results

164 NAT patients were analyzed; mean (SD) follow-up was 6 (6) months and number of assessments was 2.3 (1.6). Significant improvements from pre-NAT BL were seen in 8 of 12 NQ domains. Patients with BL impairment had significant improvements in 10 NQ domains and higher rates of improvement compared to the overall cohort (p<0.05). In this subgroup, the largest number of patients with ≥5-point improvement was seen for positive affect and well-being (PAF) (43%), emotional and behavioral dyscontrol (EBD) (38%) and sleep disturbances (35%). In the subgroup of NAT (n=145)- and OCR (n=520)-treated patients, the annualized improvement rates were higher with NAT than with OCR, reaching statistical significance for PAF (p=0.02), sleep disturbances (p=0.003), and satisfaction with social roles and activities (SRA) (p=0.03). In patients with impaired BL NQ, significantly higher rates of improvement were seen with NAT than with OCR for EBD (p=0.01), participation in SRA (p=0.0001) and satisfaction with SRA (p=0.02). The percentage of patients with ≥5-point improvement was numerically higher with NAT than OCR for 9 of 12 NQ domains; differences in the likelihood of ≥5-point improvement were not significant.

Conclusions

NAT can lead to clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias as their magnitude exceeded improvements with another high-efficacy therapy (OCR).

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Presenter Of 2 Presentations

Clinical Outcome Measures Poster Presentation

P0142 - Real-world effectiveness of dimethyl fumarate versus fingolimod using novel outcomes in a heterogeneous patient cohort (ID 708)

Speakers
Presentation Number
P0142
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Prior studies suggested comparable effectiveness of dimethyl fumarate (DMF) and fingolimod (FTY) in multiple sclerosis (MS) using relapses and traditional MRI metrics. We expanded on these assessments with new outcomes, while also accounting for comorbidities.

Objectives

Compare the real-world effectiveness of DMF vs. FTY with standardized neuroperformance, MRI, and biomarker (serum neurofilament light [sNfL]) measures.

Methods

Patients were eligible if on DMF or FTY at enrollment in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network with ≥1 year of follow up and ≥1 MRI in the previous year. Sensitivity analysis included a sub-group of patients who initiated DMF or FTY within 2 years prior to MS PATHS. Propensity score weighting model covariates included demographics, MS disease history parameters, clinical and radiographic characteristics, cardiovascular disease, and diabetes. Generalized estimating equation (GEE) models assessed the differences in means and in 1-year change in neuroperformance and MRI outcomes. Logistic regression models compared sNfL with age-adjusted normative thresholds.

Results

644 DMF and 564 FTY patients had neuroperformance data, 194-354 DMF and 201-385 FTY patients had MRI assessments, 152 DMF and 118 FTY patients had NfL samples. The number of follow-up assessments was comparable between groups (approximately 2 clinical, 2 MRI, and 1 biomarker). Mean time (SD) since treatment initiation was 2.2 (1.5) years for DMF and 2.6 (2.1) years for FTY. No differences were observed in the means or slopes of change for any of the analyzed outcomes. Differences in slopes of change were minimal for processing speed (0.06, p=0.8), manual dexterity (-0.1, p=0.5), walking speed (-0.03, p=0.7), contrast sensitivity (-0.03, p=0.9), patient-determined disease steps (0.02, p=0.5), relapses (0.001, p=0.9), brain parenchymal fraction (0.0003, p=0.3), new T2 lesions (0.3, p=0.1), Gd+ lesions (0.1, p=0.1), and grey matter fraction (0.002, p=0.2). There was no difference in the proportion of patients with elevated sNfL (p=0.12). The sub-group consisted of 123 DMF and 130 FTY patients with mean time (SD) since treatment initiation of 10.2 (6.9) and 10.9 (7.2) months, respectively. Subgroup sensitivity analyses showed similar findings.

Conclusions

DMF and FTY demonstrated similar effectiveness on standardized quantitative neuroperformance, MRI, and biomarker outcomes in a heterogeneous, real-world cohort.

Supported by: Biogen

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Patient-Reported Outcomes and Quality of Life Poster Presentation

P1036 - Impact of natalizumab on quality of life in a real-world cohort of patients with multiple sclerosis: results from MS PATHS (ID 1794)

Speakers
Presentation Number
P1036
Presentation Topic
Patient-Reported Outcomes and Quality of Life

Abstract

Background

Understanding patient-reported changes in physical, mental, and social health after starting MS therapy is important in optimizing treatment.

Objectives

Assess changes in the Quality of Life in Neurological Disorders (Neuro-QoL; NQ) questionnaire after starting natalizumab (NAT) and compare to another high efficacy therapy - ocrelizumab (OCR).

Methods

T-scores of 12 NQ domains were obtained at routine visits in the MS Partners Advancing Technology and Health Solutions (MS PATHS) network. NQ scores from visits post NAT initiation were compared to last previous NQ (baseline, BL) to calculate the annualized rate of change and the likelihood of clinically meaningful change (≥5-point) in the overall cohort and in patients with abnormal BL NQ (T-score worse than 50; 36%-76% of the population). Subgroup analyses in NAT- and OCR-treated patients were conducted with multivariate mixed-effects regression models after propensity score weighting and adjustment for antidepressants, year and drug*year interaction.

Results

164 NAT patients were analyzed; mean (SD) follow-up was 6 (6) months and number of assessments was 2.3 (1.6). Significant improvements from pre-NAT BL were seen in 8 of 12 NQ domains. Patients with BL impairment had significant improvements in 10 NQ domains and higher rates of improvement compared to the overall cohort (p<0.05). In this subgroup, the largest number of patients with ≥5-point improvement was seen for positive affect and well-being (PAF) (43%), emotional and behavioral dyscontrol (EBD) (38%) and sleep disturbances (35%). In the subgroup of NAT (n=145)- and OCR (n=520)-treated patients, the annualized improvement rates were higher with NAT than with OCR, reaching statistical significance for PAF (p=0.02), sleep disturbances (p=0.003), and satisfaction with social roles and activities (SRA) (p=0.03). In patients with impaired BL NQ, significantly higher rates of improvement were seen with NAT than with OCR for EBD (p=0.01), participation in SRA (p=0.0001) and satisfaction with SRA (p=0.02). The percentage of patients with ≥5-point improvement was numerically higher with NAT than OCR for 9 of 12 NQ domains; differences in the likelihood of ≥5-point improvement were not significant.

Conclusions

NAT can lead to clinically meaningful improvements in mental and social health. Such improvements are unlikely to be primarily driven by expectation bias as their magnitude exceeded improvements with another high-efficacy therapy (OCR).

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