Author Of 2 Presentations
FC04.02 - Effects of natalizumab on patient-reported MS outcomes using prospective data from the Australian MS longitudinal study
Abstract
Background
There is limited evidence on the effects of disease modifying therapies (DMTs) on MS symptoms, health-related quality of life (HRQoL) and employment outcomes, particularly the comparative effectiveness between different available DMTs.
Objectives
By using the prospectively collected patient-reported data in the Australian MS Longitudinal Study (AMSLS) from 2015 to 2017, we aimed to compare natalizumab to other DMTs in relation to employment outcomes, MS symptom severity, HRQoL, and progression in the previous 12 months.
Methods
Medication and Disease Course surveys were conducted in 2015, 2016 and 2017, and collected data on DMTs, severity of 13 MS symptoms (0-10 scale), disability, HRQoL by European Quality of Life with five dimensions (EQ-5D) and work productivity loss (absenteeism, presenteeism, total work productivity loss in the previous 4 weeks). We used marginal structural models to estimate causal effect of natalizumab versus other DMT comparators (any other DMT, classic injectables, oral therapies (teriflunomide and dimethyl fumarate), higher efficacy DMTs (fingolimod, alemtuzumab and mitoxantrone), fingolimod, and alemtuzumab), while adjusting for time-varying confounders and intermediates of treatment effects.
Results
The analysis included 2836 observations. Compared to any other DMTs, natalizumab was associated with superior effects over time on improving balance, vision symptoms, sensory symptoms, bladder symptoms, sexual dysfunction, and feelings of anxiety. The strongest effect was seen for improving sensory problems (mean coefficient -0.44 (-0.66 to -0.22) per year). There was no evidence of an effect of natalizumab over time on improving HRQoL measured by the EQ-5D, but use of any other DMTs were associated with a significant decrease in EQ-5D. The use of natalizumab was associated with a marginal decrease in self-reported progression in the previous 12 months while the use of injectable DMTs and fingolimod were associated with an increased self-reported progression. The use of natalizumab was associated with a reduction in work productivity loss due to absenteeism compared to a worsening for any other DMT, and similar trends were less pronounced for presenteeism and total work productivity loss.
Conclusions
Compared to other DMTs, the use of natalizumab was associated with superior effects over time for several MS symptoms and absenteeism.
SS02.04 - First results of the COVID-19 in MS Global Data Sharing Initiative suggest anti-CD20 DMTs are associated with worse COVID-19 outcomes
- S. Simpson-Yap
- E. De Brouwer
- T. Kalincik
- N. Rijke
- J. Hillert
- C. Walton
- G. Edan
- Y. Moreau
- T. Spelman
- L. Geys
- T. Parciak
- C. Gautrais
- N. Lazovski
- A. Pirmani
- A. Ardeshirdavani
- L. Forsberg
- A. Glaser
- R. McBurney
- H. Schmidt
- A. Bergmann
- S. Braune
- A. Stahmann
- R. Middleton
- A. Salter
- A. Van Der Walt
- J. Rojas
- I. Van Der Mei
- R. Ivanov
- G. Sciascia Do Olival
- A. Dias
- M. Magyari
- D. Brum
- M. Mendes
- R. Alonso
- R. Nicholas
- J. Bauer
- A. Chertcoff
- A. Zabalza
- G. Arrambide
- G. Comi
- L. Peeters
Abstract
Background
As the COVID-19 pandemic amplifies, efforts to minimise the risk on vulnerable people are essential. People with multiple sclerosis (MS) may be a vulnerable group due to the high proportion taking long-term immunosuppressive disease-modifying therapies (DMTs). Studies from Italy and France suggest older age, higher disability and progressive MS are associated with severe COVID-19, yet there remains uncertainty around the influence of DMTs.
Objectives
Given the many approved MS DMTs and the relatively low frequency of COVID-19 in MS patients per country, international data sharing is desirable to examine the impact of DMTs on COVID-19 severity. Here, we present the first results of the COVID-19 in MS global data sharing initiative of the MS International Federation and MS Data Alliance and many other data partners to inform MS clinical management during the COVID-19 pandemic.
Methods
Clinician-reported data from 21 countries were aggregated into a dataset of 1540 patients. Characteristics of admission to hospital, admission to intensive care unit (ICU), need for artificial ventilation, and death, were assessed in patients with confirmed or suspected COVID-19 infection using log-binomial regression. Adjusted prevalence ratios (aPR) were calculated adjusting for age, sex, MS type, and Expanded Disability Status Scale (EDSS).
Results
Of 1540 patients, 476 (30.9%) with suspected and 776 (50.4%) with confirmed COVID-19 were included in the analysis. Older age, progressive MS and higher EDSS were associated with higher frequencies of severe outcomes. Anti-CD20 DMTs, ocrelizumab and rituximab, were positively associated with hospital admission (aPRs=1.19 & 1.58), ICU admission (aPRs=3.53 & 4.12), and the need for artificial ventilation (aPRs=3.17 & 7.27) compared to dimethyl fumarate. Higher frequencies of all three outcomes were associated with combined anti-CD20 DMT use compared to all other DMTs (hospitalisation aPR=1.49; ICU aPR=2.55; ventilation aPR=3.05) and compared to natalizumab (hospitalisation aPR=1.99; ICU aPR=2.39; ventilation aPR=2.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases and upon exclusion of each contributing data source in turn. No associations were observed between DMTs and death.
Conclusions
This study used the largest federated international cohort of people with MS and COVID19 currently available. We demonstrate a consistent association of anti-CD20 DMTs with hospitalisation, ICU admission and use of artificial ventilation suggesting their use among MS patients at risk for COVID-19 exposure may be a risk factor for more severe COVID-19 disease. To address study limitations, further research incorporating comorbidities, smoking and body mass index is required. Alternative study designs are needed to address questions on COVID-19 susceptibility among people with MS.
Presenter Of 1 Presentation
FC04.02 - Effects of natalizumab on patient-reported MS outcomes using prospective data from the Australian MS longitudinal study
Abstract
Background
There is limited evidence on the effects of disease modifying therapies (DMTs) on MS symptoms, health-related quality of life (HRQoL) and employment outcomes, particularly the comparative effectiveness between different available DMTs.
Objectives
By using the prospectively collected patient-reported data in the Australian MS Longitudinal Study (AMSLS) from 2015 to 2017, we aimed to compare natalizumab to other DMTs in relation to employment outcomes, MS symptom severity, HRQoL, and progression in the previous 12 months.
Methods
Medication and Disease Course surveys were conducted in 2015, 2016 and 2017, and collected data on DMTs, severity of 13 MS symptoms (0-10 scale), disability, HRQoL by European Quality of Life with five dimensions (EQ-5D) and work productivity loss (absenteeism, presenteeism, total work productivity loss in the previous 4 weeks). We used marginal structural models to estimate causal effect of natalizumab versus other DMT comparators (any other DMT, classic injectables, oral therapies (teriflunomide and dimethyl fumarate), higher efficacy DMTs (fingolimod, alemtuzumab and mitoxantrone), fingolimod, and alemtuzumab), while adjusting for time-varying confounders and intermediates of treatment effects.
Results
The analysis included 2836 observations. Compared to any other DMTs, natalizumab was associated with superior effects over time on improving balance, vision symptoms, sensory symptoms, bladder symptoms, sexual dysfunction, and feelings of anxiety. The strongest effect was seen for improving sensory problems (mean coefficient -0.44 (-0.66 to -0.22) per year). There was no evidence of an effect of natalizumab over time on improving HRQoL measured by the EQ-5D, but use of any other DMTs were associated with a significant decrease in EQ-5D. The use of natalizumab was associated with a marginal decrease in self-reported progression in the previous 12 months while the use of injectable DMTs and fingolimod were associated with an increased self-reported progression. The use of natalizumab was associated with a reduction in work productivity loss due to absenteeism compared to a worsening for any other DMT, and similar trends were less pronounced for presenteeism and total work productivity loss.
Conclusions
Compared to other DMTs, the use of natalizumab was associated with superior effects over time for several MS symptoms and absenteeism.
Author Of 9 Presentations
P0104 - Long term disability trajectories in multiple sclerosis: a group-based trajectory analysis of the AusLong cohort (ID 1920)
Abstract
Background
Understanding progression of disability in multiple sclerosis (MS) is essential to design preventive and therapeutic strategies.
Objectives
We analyzed data from the Ausimmune Longitudinal (AusLong) Study to investigate the existing heterogeneity in long-term disability accumulation in a prospective cohort of People with MS (PwMS) followed over 10 years from the date of their first clinical diagnosis (FCD) and identify clinical and demographic factors associated with these trajectories.
Methods
We used a group-based trajectory model (GBTM) to measure the heterogeneity in the disability trajectories based on Expanded Disability Status Scale (EDSS) in a prospective cohort of 263 participants followed from FCD.
Results
We identified three distinct clinically meaningful disability trajectories: no or mild, moderate and severe disability trajectories. Those in the minimal disability trajectory did not show any appreciable progression of disability (median EDSS ~ 1 at 10-year review), those in moderate and severe disability trajectories experienced disability worsening (median EDSS~ 2.5 and 6, respectively). The relative probability of being in a worsening disability trajectory was higher for older age at onset, those experiencing a higher number of relapses within five-year post FCD and those having a shorter interval between the first two attacks. High annual relapse rate was associated with an upward shift in moderate disability trajectory, whereas non-smoking status was associated with reducing the EDSS score in minimal and severe disability trajectories.
Conclusions
Those at highest risk of rapid disability progression can be identified based on their early clinical information with potential therapeutic implications.
P0432 - Assessment of Depression, Anxiety and Fatigue in relation to diet quality in Multiple Sclerosis (ID 120)
Abstract
Background
Many people with multiple sclerosis (MS) modify their dietary intake, but there is low evidence that this influences MS disease activity or progression.
Objectives
We examined whether indices of diet quality (Dietary Quality Tracker and Australian Recommended Food Score) were associated with depression, anxiety and fatigue using a prospective cohort.
Methods
The Auslong Study participants were followed annually for 10 years (n=223 with MS at 10 years). Depression & anxiety (Hospital Anxiety & Depression Scale, HADS) and fatigue (Fatigue Severity Scale) were assessed at the 5th and 10th-year reviews. Dietary intake in the preceding 12 months using the Cancer Council Victoria Food Frequency Questionnaire was assessed at the baseline, 5th and 10th year reviews.
Results
Overall diet quality at the 5th-year review was not associated with a change in depression, anxiety or fatigue in the subsequent 5 years. However, a higher intake of protein, grain and discretionary foods at the 5th-year review using the Dietary Quality Tracker were associated with an increase in HADS depression score over the subsequent 5 years (e.g. highest vs lowest quartile protein: β=2.14,95%CI=0.91,3.37,p<0.001). Also, a higher legume intake at the 5th-year review was associated with a decrease in HADS anxiety score over the subsequent 5 years( e.g. highest vs lowest quartile: β=-1.92,95%CI=-3.32,-0.53,p=0.01).
Conclusions
Overall diet quality was not associated with a subsequent change in depression, anxiety or fatigue over 5-years but some specific food groups were associated with depression and anxiety. Replication is required before testing these findings with diet intervention programs in people with MS.
P0450 - Comorbidity patterns in people with multiple sclerosis: A latent class analysis of the Australian Multiple Sclerosis Longitudinal Study (ID 1065)
Abstract
Background
Published studies are designed towards identifying the impact of the total number and individual comorbidities, and therefore limited knowledge exists on the comorbidity patterns and their influence on people with multiple sclerosis (MS).
Objectives
To identify the comorbidity patterns and examine their association with the sociodemographic characteristics of people with MS.
Methods
We conducted latent class analysis (LCA) to identify clinically distinct comorbidity classes in PwMS using the 15 most common comorbidities among 1,518 Australian Multiple Sclerosis Longitudinal Study (AMSLS) participants. The associations between comorbidity classes and sociodemographic characteristics were explored using multinomial logistic regression.
Results
Five classes with distinct comorbidity patterns were identified: “minimally-diseased class” (30.8%) for participants with no or one comorbidity; “metabolic class” (22.7%), “mental health-allergy class” (21.7%), “non-metabolic class” (7.6%) or “severely-diseased class” (7.0%) for participants with higher prevalence of comorbidities. The relative probability (relative risk ratios, 95%CI) of being assigned to other comorbidity classes over the “minimally-diseased class” were significantly increased for participants who were older (metabolic: 1.09 (1.06-1.11); non-metabolic: 1.07 (1.04-1.11); severely-diseased: 1.04 (1.01-1.08)), female (non-metabolic: 5.35 (1.98-14.42); severely-diseased: 2.21 (1.02-4.77)), obese (metabolic: 4.06 (2.45-6.72); mental health-allergy: 1.57 (1.00-2.46); severely-diseased: 4.53 (2.21-9.29)) and had moderate disability (mental health-allergy: 2.32 (1.47-3.64); severely-diseased: 2.65 (1.16-6.04)).
Conclusions
Comorbidities in MS tend to cluster into distinct disease patterns and are associated with some demographics and clinical characteristics. Understanding comorbidity patterns in MS may be used to design more appropriate comorbidity prevention and management strategies.
P0471 - Intra-individual variations in multiple sclerosis symptoms are associated with changes in work productivity of people living with multiple sclerosis (ID 1721)
Abstract
Background
Multiple sclerosis (MS) symptoms are associated with MS-related work productivity loss. But it is unknown whether changes in MS symptoms would lead to changes in work productivity in people living with MS (PwMS).
Objectives
To determine whether intra-individual variations in MS symptoms over time are associated with corresponding changes in work productivity in PwMS.
Methods
Study participants were employed Australian MS Longitudinal Study (AMSLS) participants followed from 2015 to 2019 with at least two repeated measures (n=2121). We used mixed effect models to examine if the within-individual variations in MS symptoms are associated with changes in work productivity.
Results
The mean annual change in work productivity between 2015 and 2019 was -0.23% (SD = 18.68%), with 39% experiencing no change, 31% decreasing in work productivity and 30% increasing in work productivity. Our analysis showed that disability and symptom scores at the start of the year were not associated with subsequent annual change in work productivity. However, the annual change in disability and annual change in symptom severity clusters were associated with the annual change in work productivity in the same year. In a multivariable model, annual change in ‘pain and sensory symptoms’, ‘feelings of anxiety and depression’, and ‘fatigue and cognitive symptom’ were independently associated with annual change in work productivity. Every unit increase in mean annual change of the symptom clusters were associated with 2.44%, 1.57% and 1.01% annual reduction in work productivity, respectively.
Conclusions
Individual change in work productivity seems to be driven by the changes in symptom severity rather than the absolute severity. To improve work productivity, management should focus on stabilising or improving symptoms.
P0498 - The effect of national disease modifying therapy subsidy policy on long-term disability outcomes in people with multiple sclerosis (ID 1652)
Abstract
Background
Disease-modifying therapies (DMT), which modify, mediate or suppress the immune system, are a major medication class for treating people with relapsing-onset multiple sclerosis (MS). However, our knowledge about these medications is largely limited to their short-term effects.
Objectives
To determine: 1) the impact of national-level DMT subsidy policy on DMT use and disability in people living with MS (PwMS); and 2) the long-term effects of DMT on disability (EDSS and MSSS) and quality of life (EQ5D5L utility score).
Methods
This project was an ecological, observational cohort study comparing populations in Australia and New Zealand with similar demographics, but markedly different levels of DMT use 10-20 years post-diagnosis. Differences between countries were assessed using standardized differences (Cohen’s d), phi coefficient and Cramer’s V. Associations were assessed with univariable and multivariable (mediation) linear regression models.
Results
We recruited 328 Australian participants, 93.9% of whom had been treated with DMT, and 256 New Zealand participants, 50.4% of whom had been treated with DMT. The Australian cohort had a longer median treatment duration (148 vs 0 months), greater proportion of disease course treated (86% vs 0%), and shorter time between diagnosis and first DMT (3 vs 24 months). The Australian cohort also had lower median EDSS (3.5 vs 4.0) and MSSS (3.05 vs 3.71), and higher quality of life (0.71 vs 0.65) at follow-up. In multivariable models, differences in DMT use significantly mediated the effect of country on disability and quality of life.
Conclusions
This large ecological study provides evidence for the impact of national level policy on DMT use and subsequent disability outcomes in PwMS. It also demonstrates that the protective effect of DMT may mediate the effect of national policy on disability progression and quality of life 10-20 years post-diagnosis in people with relapsing-onset MS.
P0504 - The relative contribution of comorbidities on the severity of symptoms in people with Multiple Sclerosis (ID 1064)
Abstract
Background
The symptoms reported by people with Multiple Sclerosis (MS) vary greatly and are influenced by comorbidities, but our understanding on the contribution of comorbidities on MS symptomatology remains limited.
Objectives
To examine the dose-response relationship between the number of comorbidities and symptoms severity and to assess the relative contribution of comorbidity groups and individual comorbidities to symptoms severity.
Methods
Cross-sectional analysis of data on the presence of 30 comorbidities and the severity of 13 most common symptoms (0-10 scale) of the Australian Multiple Sclerosis Longitudinal Study participants (n=1,223). The dose-response relationship between comorbidities and symptoms severity were assessed using negative binomial regression. The relative contribution of comorbidities to the severity of symptoms was assessed using general dominance analysis.
Results
Higher number of comorbidities was most strongly associated with a higher severity in feelings of anxiety, feelings of depression and pain (ratios of means >0.12 per comorbidity increase). Comorbidities explained between 3.7% (spasticity) and 22.0% (feelings of anxiety) of the total variance of symptoms severity variables. Mental health disorders contributed most strongly to the severity of 6/13 symptoms (feelings of anxiety, feelings of depression, cognitive symptoms, sensory symptoms, fatigue and sexual dysfunction). Musculoskeletal disorders contributed most strongly to the severity of another 6/13 symptoms (pain, walking difficulties, difficulty with balance, bladder problems, bowel problems and spasticity).
Conclusions
Our findings support that early recognition and optimal management of comorbidities, particularly of mental health and musculoskeletal disorders, could have a positive impact on the severity of symptom of people with MS.
P0513 - Work productivity trajectories in Australians living with multiple sclerosis: a group-based modelling approach (ID 1737)
Abstract
Background
Studies have documented loss of work capacity and work productivity loss in multiple sclerosis (MS). Little is known about the longitudinal trajectories of work productivity in MS.
Objectives
To explore trajectories of work productivity in people living with multiple sclerosis (PwMS) and examine the baseline factors associated with assignment to the trajectories group.
Methods
Study participants were from the Australian MS Longitudinal Study (AMSLS) from 2015 to 2019 who were employed and had more than two follow-ups (n=2121). We used group-based trajectory modelling to identify unique work productivity trajectories in PwMS. Multinomial logistic regression was used to assess associations with the work productivity trajectories.
Results
We identified three distinct trajectories of work productivity: ‘moderately worsened’ (16.7% of participants) with a mean work productivity of 47.6% in 2015, ‘mildly worsened’ (50.1%) with a mean work productivity of 86.3% in 2015 and ‘normal’ (33.2%) with a mean work productivity of 99.7% in 2015. The relative probability of being in a moderately or mildly worsened work productivity trajectory were higher for those with a higher education level, baseline work productivity, and high MS symptom severity. For example, the relative probability of being in ‘moderately worsened’ rather than ‘normal’ work productivity trajectory increased by 36% (RRR:1.36 ; 95% confidence interval:1.09 –1.71) for each unit increase in ‘fatigue and cognitive symptoms’ cluster.
Conclusions
Higher education level, and MS symptom severity increased the relative probability of following a low work productivity trajectory. Work productivity interventions should target MS symptoms severity and disability reduction.
P1032 - Feelings of depression, pain and walking difficulties have the largest impact on the quality of life of people with MS, irrespective of MS phenotype (ID 761)
Abstract
Background
The symptoms that have the largest impact on health-related quality of life (HRQoL) in people with multiple sclerosis (MS) may vary by MS phenotype (relapsing-remitting MS, RRMS; secondary progressive MS, SPMS; primary progressive MS, PPMS). Knowing these symptoms assists in symptom management.
Objectives
To examine the associations between 13 common MS symptoms and HRQoL in the total sample and stratified by MS phenotype.
Methods
The study included 1,985 participants. HRQoL was measured with two multi-attribute utility instruments: Assessment of Quality of Life with eight dimensions (AQoL-8D) and European Quality of Life with five dimensions and five levels (EQ-5D-5L). Multivariable linear regression was used to identify the symptoms that had the largest impact on the HRQoLs.
Results
Feelings of depression, pain, fatigue, and feelings of anxiety were most strongly associated with AQoL-8D and EQ-5D-5L. Walking difficulties additionally contributed to reduced EQ-5D-5L. The strongest single predictors were feelings of depression or pain for AQoL-8D and walking difficulties for EQ-5D-5L, irrespective of MS phenotype.
Conclusions
The strongest single predictors for the AQoL-8D and EQ-5D-5L were feelings of depression, pain, and walking difficulties, irrespective of MS phenotype. Reducing these symptoms may have the largest impact on improving HRQoL in all MS phenotypes of people with MS.
P1037 - Impact of remoteness on patient-reported outcomes in Australians with multiple sclerosis (ID 1550)
Abstract
Background
Inequity in the availability and quality of health care may exist across geographical locations. Little is known about whether living in remote areas is associated with worse health outcomes in Australians with multiple sclerosis (MS), which is important information for health care planning.
Objectives
We aimed to evaluate whether living in regional or remote areas was associated with worse disease outcomes, employment outcomes, health-related quality of life (HRQoL), disease modifying therapy (DMT) utilisation and cost of illness among Australians with MS.
Methods
Around 3000 participants of the Australian MS Longitudinal Study were invited to participate in three surveys in 2016. Level of remoteness (major cities, inner regional, outer regional, remote and very remoted Australia) was determined using postcode. Information on MS type, DMT use, HRQoL, severity of 13 MS symptoms, disability and employment outcomes were collected. Data were analysed using linear regression, log-binomial regression, log-multinomial regression and negative binomial regression.
Results
Living in more remote areas was not associated with substantially worse health/employment outcomes, or higher MS costs among Australians with MS. There was a consistent pattern of those living in inner regional areas having slightly worse health outcomes and higher costs, but the effect sizes were relatively small and there were no clear dose-response relationships with increasing remoteness. They were also less likely to use high efficacy DMTs compared to those living in major cities. Adjusting for factors such as age, disease duration, and education level only marginally reduced the associations.
Conclusions
There is no large inequity in outcomes within the Australian MS population as a result of remoteness, although those living in inner regional areas had slightly worse health outcomes and higher MS costs.
Presenter Of 1 Presentation
P1037 - Impact of remoteness on patient-reported outcomes in Australians with multiple sclerosis (ID 1550)
Abstract
Background
Inequity in the availability and quality of health care may exist across geographical locations. Little is known about whether living in remote areas is associated with worse health outcomes in Australians with multiple sclerosis (MS), which is important information for health care planning.
Objectives
We aimed to evaluate whether living in regional or remote areas was associated with worse disease outcomes, employment outcomes, health-related quality of life (HRQoL), disease modifying therapy (DMT) utilisation and cost of illness among Australians with MS.
Methods
Around 3000 participants of the Australian MS Longitudinal Study were invited to participate in three surveys in 2016. Level of remoteness (major cities, inner regional, outer regional, remote and very remoted Australia) was determined using postcode. Information on MS type, DMT use, HRQoL, severity of 13 MS symptoms, disability and employment outcomes were collected. Data were analysed using linear regression, log-binomial regression, log-multinomial regression and negative binomial regression.
Results
Living in more remote areas was not associated with substantially worse health/employment outcomes, or higher MS costs among Australians with MS. There was a consistent pattern of those living in inner regional areas having slightly worse health outcomes and higher costs, but the effect sizes were relatively small and there were no clear dose-response relationships with increasing remoteness. They were also less likely to use high efficacy DMTs compared to those living in major cities. Adjusting for factors such as age, disease duration, and education level only marginally reduced the associations.
Conclusions
There is no large inequity in outcomes within the Australian MS population as a result of remoteness, although those living in inner regional areas had slightly worse health outcomes and higher MS costs.