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Background: Multiple sclerosis (MS) prevalence is increasing globally., Objectives: To determine whether increased prevalence is continuing within Australia using our validated prescription-based ascertainment method., Methods: We used methods employed in our 2010 and 2017 prevalence estimates. Disease-modifying therapy (DMT) prescriptions were extracted from Australia's Pharmaceutical Benefits Scheme data for January-December 2021. DMT penetrance was calculated using data from the Australian MS Longitudinal Study. We divided the total number of monthly prescriptions by 12 or 2 (except alemtuzumab), adjusted for DMT penetrance and Australian population estimates. Prevalences in Australian states/territories were age-standardised. 2021 prevalence estimates were compared with 2010 and 2017 prevalence estimates using Poisson regression., Results: Number of people with MS in Australia in 2021 was 33,335; an increase of 7728 from 2017 (30.2%) and 12,092 from 2010 (56.6%) and increasing at a faster rate than population change (+10.1%, +14.1%). Age-standardised prevalence was 136.1/100,000 (increased from 103.7/100,000 in 2017). The previously demonstrated positive latitudinal gradient in 2010 and 2017 persisted in 2021, with Tasmania (southernmost state) having the highest prevalence (age-standardised: 203.5/100,000) while northernmost states had the lowest., Conclusions: In line with global trends, MS prevalence is escalating in Australia, particularly in higher-latitude states. MS prevention is crucial to halt this disturbing trend., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS., Objective: We examined whether Dietary Inflammatory Index (DII ®) ) scores are associated with measures of MS progression and inflammatory activity., Methods: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n  = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DII TM ) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume., Results: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = -1.16, 4.33, p  = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (β = 0.38, 95% CI = 0.04, 0.72, p  = 0.03)., Conclusion: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.

Background: People with multiple sclerosis face significant employment-related challenges, with little known of the drivers of these outcomes., Objective: We examined prospective trajectories of employment-related outcomes up to 11 years following a first episode of central nervous system (CNS) demyelination (FCD)., Methods: Participants were aged 18-59 years, at FCD, with at least two observations and were employed at study entry or anytime during follow-up ( n  = 207). Outcomes were employment status (full-time, part-time and unemployed), average workhours per week and disability support pension (DSP; receiving/not receiving). We used group-based trajectory modelling to identify groups with common trajectories. Factors associated with trajectory membership were explored using log-multinomial regression., Results: Distinct trajectories were identified for employment (4), workhours (4) and DSP (2). Compared with stable full-time, female sex was strongly associated with being in the stable part-time trajectory (risk ratio (RR): 5.35; 95% confidence interval (CI) = 2.56-11.20; p  < 0.001). A greater level of disability at 5-year review (RR: 1.35; 95% CI = 1.19-1.53) and having more than two comorbidities at baseline (RR: 2.77; 95% CI = 1.37-5.64) were associated with being in early and late deteriorated employment trajectories, respectively. Compared with the increased part-time trajectory, every additional relapse during the 5 years post-FCD was associated with a 10% increased risk of being in the reduced part-time trajectory (RR = 1.10; 95%CI = 1.00-1.22). For every additional EDSS point at 5-year review, the risk of being in the DSP trajectory increased (RR = 1.21; 95% CI = 1.05-1.41)., Conclusion: These trajectories indicate substantial heterogeneity and the complex impact of MS on employment from its earliest timepoints. Understanding these trends could enable better targeting of interventions to facilitate workforce retention, particularly for females, those with a higher number of comorbidities, more frequent relapses and greater rate of disability accrual.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Background: Disease-modifying therapies (DMTs) are used to treat people with relapsing-onset multiple sclerosis (ROMS), but our knowledge is largely limited to their short-term effects., Objective: To determine (1) the impact of national-level DMT subsidy policy on DMT use and health outcomes in people with MS (PwMS) and (2) the long-term effects of DMT on disability and quality of life (QoL; 5-level EQ-5D version (EQ-5D-5L) utility value)., Methods: This observational cohort study compared Australian and New Zealand populations with different levels of DMT availability 10-20 years post-ROMS diagnosis. Between-country differences were assessed using standardised differences. Associations were assessed with multivariable linear regression models., Results: We recruited 328 Australians and 256 New Zealanders. The Australian cohort had longer DMT treatment duration, greater proportion of disease course treated and shorter duration between diagnosis and starting DMT. The Australian cohort had lower median Expanded Disability Status Scale (EDSS) (3.5 vs 4.0) and Multiple Sclerosis Severity Score (MSSS) (3.05 vs 3.71) and higher QoL (0.71 vs 0.65). In multivariable models, between-country differences in disability and QoL were largely attributed to differential use of DMT., Conclusions: This study provides evidence for the impact of national-level DMT policy on disability outcomes in PwMS. Where DMTs are more accessible, PwMS experienced less disability progression and improved QoL 10-20 years post-diagnosis.

Background: Genome-wide association studies (GWAS) have succeeded in identifying over 200 susceptibility loci for multiple sclerosis (MS). However, the potential functional variants and the mechanisms by which these loci affect MS risk remain largely unexplained., Objectives: We used summary data-based Mendelian randomisation to prioritise risk genes and infer potential biological mechanisms for MS risk loci., Methods: The data used consisted of DNA methylation ( n = 1980) QTL (mQTL) and gene expression ( n = 31,684) QTL (eQTL) derived from whole blood as well as MS GWAS summary statistics (14,802 cases, 26,703 controls). The findings were further evaluated using data derived from independent brain mQTL ( n = 1160) and eQTL ( n = 1194)., Results: In whole blood, we identified two independent genomic loci (lincRNA: RP11-326C3.13 and TNFSF14 ) with consistent genome-wide significant pleiotropic associations across different omics layers. In brain tissue, a similar effect for the RP11-326C3.13 locus was observed but not for TNFSF14 , indicating a potential tissue-specific effect for the TNFSF14 locus., Conclusion: We provide in silico evidence for the putative biological mechanisms by which the identified DNA methylation sites and target genes are functionally relevant to MS development in different tissues. Future research targeting these genes and DNA methylation sites will determine their roles in the pathophysiology of MS.

Background: No studies have assessed changes in employment survival in multiple sclerosis (MS) populations over recent decades, including the introduction of disease-modifying therapies (DMTs)., Objectives: To evaluate factors associated with leaving employment due to MS; to assess whether the risk of leaving employment has changed over recent decades in Australia, stratified by MS phenotype., Methods: We included 1240 participants who were working before MS diagnosis. Information on employment status, reasons for leaving employment and year of leaving were collected. Data were analysed using competing risk survival analysis., Results: Males, progressive MS, lower education level and older age at diagnosis were associated with a higher sub-distribution hazard of leaving employment. Compared to the period before 2010, the sub-distribution hazard during 2010-2016 for relapsing-remitting multiple sclerosis (RRMS) was reduced by 43% (sub-distribution hazard ratio (sHR) 0.67, 95% confidence interval (CI): 0.50 to 0.90), while no significant reduction was seen for primary-progressive multiple sclerosis (PPMS) (sHR 1.25, 95% CI: 0.72 to 2.16) or secondary-progressive multiple sclerosis (SPMS) (sHR 1.37, 95% CI: 0.84 to 2.25)., Conclusion: Males, people with progressive MS and those of lower education level were at higher risk of leaving employment. The differential changed risk of leaving employment between people with different MS phenotype after 2010 coincides with the increased usage of high-efficacy DMTs for RRMS.

Background: Dietary patterns and their association with subsequent clinical course have not been well studied in early multiple sclerosis (MS)., Objectives: To describe dietary patterns in people in 5 years following first clinical demyelination and assess associations with MS conversion and relapse., Methods: This study included baseline food frequency questionnaire dietary intake (entry to the Ausimmune Study) and 5-year follow-up; iterated principal factor analysis was applied. MS conversion and relapse risks were assessed by Cox proportional hazards models, adjusted for age, sex, study site, education, body mass index (BMI), smoking and omega-3 supplement use., Results: In cases with a first clinical diagnosis of central nervous system (CNS) demyelination, we identified three major dietary patterns, 'Prudent', 'High-Vegetable' and 'Mixed', explaining 43%, 37% and 24% of diet variance in dietary intake, respectively. Fruits, vegetables, fish, wholegrains and nuts loaded highly on the Prudent pattern, starchy vegetables and legumes on the High-Vegetable pattern, and meats and alcohol on the Mixed pattern. Diet factor scores were not associated with MS conversion risk. Those with baseline Prudent scores above the median had significantly lower relapse risk (adjusted hazard ratio = 0.54, 95% confidence interval (CI) 0.37, 0.81) with some evidence of a plateau effect., Conclusion: Prudent diet factor score above the median was prospectively associated with lower relapse risk in the 5 years following the first clinical demyelinating event.

Background: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale., Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible., Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale., Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process., Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.