Updated Multiple Sclerosis Incidence, 2015-2022.

This cohort study uses population-based claims data to provide an update of multiple sclerosis incidence in Germany.

Investigation of health care use and a possible prodrome before the first attack in NMOSD and MOGAD.

BACKGROUND: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data. METHODS: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models. RESULTS: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25-1.73; aRR: 1.67; 95% CI: 1.19-2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack. CONCLUSION: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible.

Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis.

BACKGROUND: The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. METHODS: We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. RESULTS: Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%-53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. CONCLUSIONS: Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Multiple sclerosis (MS) is a disease where the immune system attacks the protective covering of nerve cells in the brain. There may be a relationship between diet and bacteria within the gut and MS, however this is not well understood. We investigated how diet and gut bacteria are linked to MS in young people. We examined the diet and types of bacteria in stool samples from those with and without MS. We found that a diet richer in fiber and Mediterranean foods were less common in those with MS. This dietary pattern was linked to certain differences in the gut bacteria. These findings raise the possibility, but cannot prove, that what we eat may help prevent MS by influencing our gut bacteria. This research opens the door to further studies on how diet can impact MS through our gut bacteria.

Meta-analysis identifies common gut microbiota associated with multiple sclerosis.

BACKGROUND: Previous studies have identified a diverse group of microbial taxa that differ between patients with multiple sclerosis (MS) and the healthy population. However, interpreting findings on MS-associated microbiota is challenging, as there is no true consensus. It is unclear whether there is gut microbiota commonly altered in MS across studies. METHODS: To answer this, we performed a meta-analysis based on the 16S rRNA gene sequencing data from seven geographically and technically diverse studies comprising a total of 524 adult subjects (257 MS and 267 healthy controls). Analysis was conducted for each individual study after reprocessing the data and also by combining all data together. The blocked Wilcoxon rank-sum test and linear mixed-effects regression were used to identify differences in microbial composition and diversity between MS and healthy controls. Network analysis was conducted to identify bacterial correlations. A leave-one-out sensitivity analysis was performed to ensure the robustness of the findings. RESULTS: The microbiome community structure was significantly different between studies. Re-analysis of data from individual studies revealed a lower relative abundance of Prevotella in MS across studies, compared to controls. Meta-analysis found that although alpha and beta diversity did not differ between MS and controls, a higher abundance of Actinomyces and a lower abundance of Faecalibacterium were reproducibly associated with MS. Additionally, network analysis revealed that the recognized negative Bacteroides-Prevotella correlation in controls was disrupted in patients with MS. CONCLUSIONS: Our meta-analysis identified common gut microbiota associated with MS across geographically and technically diverse studies.

Assessment of dietary intake and its inflammatory potential in persons with pediatric-onset multiple sclerosis.

OBJECTIVE: To compare diet and the modified dietary inflammatory index (mDII) between individuals with pediatric-onset multiple sclerosis (PoMS), monophasic acquired demyelinating syndromes (monoADS), and controls. METHODS: The association between diet, mDII, and disease status was examined in 131 individuals with PoMS/monoADS/controls (38/45/48) using logistic regression. RESULTS: The associations between diet and PoMS were modest, reaching significance for whole grain intake (adjusted odds ratio, aOR=0.964, 95 % confidence intervals, CI:0.934-0.995) but not mDII (aOR=1.20, 95 %CI:0.995-1.46) versus controls. No findings for monoADS reached significance versus controls. CONCLUSIONS: Individuals with PoMS, but not monoADS, had lower dietary whole grain intake than controls.

Incidence rate and prevalence of pediatric-onset multiple sclerosis in Sweden: A population-based register study.

BACKGROUND AND PURPOSE: Pediatric-onset multiple sclerosis (PoMS) is associated with high health care use. To plan resource allocation for this patient group, knowledge of the incidence rate and prevalence is important. However, such studies are scarce, few are population-based, and the methodology varies widely. We aimed to address this knowledge gap by performing a nationwide study of the incidence rate and prevalence of PoMS in Sweden, an area of high multiple sclerosis (MS) incidence and prevalence. METHODS: MS cases were identified by linking two nationwide registers, the National Patient Register and the Swedish MS Registry. MS cases having their first central nervous system demyelinating event or MS clinical onset before age 18 years were classified as pediatric onset. Incidence rate and prevalence were estimated annually over the study period (2006-2016) for the total population and stratified by sex and age group (<12, 12-15, and 16-17 years). Temporal trends and ratios between sexes and age groups were estimated. RESULTS: We identified 238 incident cases from 2006 to 2016, corresponding to an overall crude incidence rate of 1.12 per 100,000 person-years and an overall crude prevalence of 2.82 per 100,000 population. There was a higher incidence rate among females and the highest age category. The overall incidence rate and prevalence estimates remained stable during the study period. CONCLUSIONS: Sweden exhibits a consistently high incidence rate and prevalence of PoMS that has remained stable over time. This knowledge serves as a tool to aid in planning resource allocation and health services for this patient population.

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study

BACKGROUND AND OBJECTIVES: It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study. METHODS: We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised ß-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models. RESULTS: We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%-61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%-33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29-36.51), hypertension 4.96 (95% CI 1.78-13.84), and cardiovascular disease 3.72 (95% CI 2.12-6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24-2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27-3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10-2.44) and hypertension (aHR 1.73; 95% CI 1.30-2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11-4.74), chronic liver disease (aHR 1.94; 95% CI 1.19-3.18), hypertension (aHR 1.76; 95% CI 1.32-2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07-2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96-21.87). DISCUSSION: Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospitalizations, there are increased risks of infection-related physician visits and incident adverse events for select DMDs.

Disease-modifying drugs, multiple sclerosis and infection-related healthcare use in British Columbia, Canada: a population-based study.

Background: Much remains unknown surrounding the disease-modifying drugs (DMDs) used to treat multiple sclerosis and infection-related healthcare use in the 'real-world' setting. We examined if DMD exposure was associated with altered infection-related healthcare use. Methods: We assessed if DMD (versus no) exposure was associated with altered infection-related hospitalizations, physician claims, and prescriptions filled in British Columbia, Canada (1996-2017). Healthcare use was assessed using negative binomial and proportional means regression models, reported as sex-/age-/comorbidity-/calendar year-/socioeconomic-adjusted rate and hazard ratios [aRR, aHR], with 95% confidence intervals [CIs]). Findings: We identified 19,360 multiple sclerosis cases (13,940/19,360; 72.0% women; mean age at study start = 44.5 standard deviation, SD = 13.3; mean follow-up = 11.7 [SD = 7.3] years). Relative to unexposed periods, exposure to any DMD was associated with a lower infection-related rate of physician claims (aRR = 0.88; 95% CI:0.85-0.92) and hazard of hospitalization (aHR = 0.64; 95% CI:0.56-0.73), and a higher rate of infection-related prescriptions (aRR = 1.14; 95% CI:1.08-1.20). Exposure to any injectable or oral DMD was associated with a lower infection-related rate of physician claims (injectable aRR = 0.88; 95% CI:0.84-0.92, oral aRR = 0.83; 95% CI:0.77-0.90) and hazard of hospitalization (injectable aHR = 0.65; 95% CI:0.56-0.75, oral aHR = 0.54; 95% CI:0.38-0.77), whereas intravenous DMD exposure was not (aRR = 0.99; 95% CI:0.86-1.14, aHR = 0.73; 95% CI:0.49-1.09). Exposure to any injectable or intravenous DMD was associated with a higher rate of infection-related prescriptions (injectable aRR = 1.15; 95% CI:1.08-1.22, intravenous = 1.34; 95% CI:1.15-1.56), whereas oral DMDs were not (aRR = 0.98; 95% CI:0.91-1.05). Interpretation: DMD exposure for the treatment of MS was associated with differences in infection-related healthcare use. While infection-related hospitalizations and physician visits were lower, prescription fills were higher. How these differences in infection-related healthcare use affect outcomes in persons with multiple sclerosis warrants consideration. Funding: Canadian Institutes of Health Research (CIHR); German Research Foundation (DFG).

Multiple Sclerosis Risk Among Anti-tumor Necrosis Factor Alpha Users: A Methodological Review of Observational Studies Based on Real-world Data.

Epidemiologic studies on the risk of multiple sclerosis (MS) or demyelinating events associated with anti-tumor necrosis factor alpha (TNFα) use among patients with rheumatic diseases or inflammatory bowel diseases have shown conflicting results. Causal directed acyclic graphs (cDAGs) are useful tools for understanding the differing results and identifying the structure of potential contributing biases. Most of the available literature on cDAGs uses language that might be unfamiliar to clinicians. This article demonstrates how cDAGs can be used to determine whether there is a confounder, a mediator or collider-stratification bias and when to adjust for them appropriately. We also use a case study to show how to control for potential biases by drawing a cDAG depicting anti-TNFα use and its potential to contribute to MS onset. Finally, we describe potential biases that might have led to contradictory results in previous studies that examined the effect of anti-TNFα and MS, including confounding, confounding by contraindication, and bias due to measurement error. Clinicians and researchers should be cognizant of confounding, confounding by contraindication, and bias due to measurement error when reviewing future studies on the risk of MS or demyelinating events associated with anti-TNFα use. cDAGs are a useful tool for selecting variables and identifying the structure of different biases that can affect the validity of observational studies.

Incidence and prevalence of paediatric-onset multiple sclerosis in two Canadian provinces: a population-based study representing over half of Canada's population.

BACKGROUND: Population-based studies estimating the epidemiology of paediatric-onset multiple sclerosis (PoMS) are scarce. METHODS: We accessed population-based health administrative data from two provinces in Canada, Ontario and British Columbia (BC). Individuals with PoMS were identified via a validated case definition. The index date ('MS onset') was the first demyelinating or MS specific claim recorded ≤18 years of age. We estimated the age-standardised annual incidence and prevalence of PoMS, and 95% CIs between 2003 and 2019. We used negative binomial regression models to assess the temporal changes in the annual crude incidence and prevalence of PoMS, and the ratios comparing sex groups. RESULTS: From 2003 to 2019, a total of 148 incident PoMS cases were identified in BC, and 672 in Ontario. The age-standardised annual incidence of PoMS was stable in both provinces, averaging 0.95 (95% CI 0.79 to 1.13) in BC and 0.98 (95%CI 0.84 to 1.12) in Ontario per 100 000 person-years. The incidence ratio by sex (female vs male) was also stable over the study period, averaging 1.5:1 (95% CI 1.06 to 2.08, BC) and 2.0:1 (95% CI 1.61 to 2.59, Ontario). The age-standardised prevalence per 100 000 people rose from 4.75 (2003) to 5.52 (2019) in BC and from 2.93 (2003) to 4.07 (2019) in Ontario, and the increase was statistically significant in Ontario (p=0.002). There were more female prevalent PoMS cases than males in both provinces. CONCLUSIONS: Canada has one of the highest rates of PoMS globally, and the prevalence, but not incidence, has increased over time. Allocation of resources to support the growing youth population with MS should be a priority.

Short-chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset.

OBJECTIVE: The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric-onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. METHODS: A multicenter case-control study in which 35 pediatric-onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self-reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co-occurrence networks and for predicting functional abundances based on marker gene sequences. RESULTS: Two microbial co-occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short-chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family-level findings from an independent Canadian-US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding. INTERPRETATION: Our results suggest that short-chain fatty acid producers may be important contributors to multiple sclerosis onset.

Disease-modifying therapies used to treat multiple sclerosis and the gut microbiome: a systematic review.

BACKGROUND: The gut microbiome may play a role in multiple sclerosis (MS). However, its relationship with the disease-modifying therapies (DMTs) remains unclear. We systematically reviewed the literature to examine the relationship between DMTs and the gut microbiota among persons with MS (pwMS). METHODS: MEDLINE, EMBASE, Web of Science, and Scopus were searched (01/2007-09/2022) for studies evaluating potential gut microbiota differences in diversity, taxonomic relative abundances, and functional capacity between DMT-exposed/unexposed pwMS or before/after DMT initiation. All US FDA-approved MS DMTs (1993-09/2022) and rituximab were included. RESULTS: Of the 410 studies, 11 were included, totalling 1243 pwMS. Of these, 821 were DMT exposed and 473 unexposed, including 51 assessed before/after DMT initiation. DMT use duration ranged from 14 days to > 6 months. No study found a difference in gut microbiota alpha-diversity between DMT exposed/unexposed (p > 0.05). One study observed a difference in beta-diversity between interferon-beta users/DMT non-users (weighted UniFrac, p = 0.006). All studies examined taxa-level differences, but most (6) combined different DMTs. Two or more studies reported eight genera (Actinomyces, Bacteroides, Clostridium sensu stricto 1, Haemophilus, Megasphaera, Pseudomonas, Ruminiclostridium 5, Turicibacter) and one species (Ruthenibacterium lactatiformans) differing in the same direction between DMT exposed/unexposed. DMT users had lower relative abundances of carbohydrate degradation and reductive tricarboxylic acid cycle I pathway than non-users (p < 0.05), but findings could not be attributed to a specific DMT. DISCUSSION: While DMT use (versus no use) was not associated with gut microbiota diversity differences, taxa-level differences were observed. Further work is warranted, as most studies were cross-sectional, few examined functionality, and DMTs were combined.

Comorbidity in the multiple sclerosis and neuromyelitis optica spectrum disorders population: findings from an underserved, low income country, Zambia.

BACKGROUND: Comorbidities are common in multiple sclerosis (MS); little is known in neuromyelitis optica spectrum disorders (NMOSD) or outside high-income regions. OBJECTIVE: Compare comorbidities in MS/NMOSD patients, Zambia. METHODS: Comorbidities were compared for MS/NMOSD patients from Zambia's University Teaching Hospital using logistic regression. RESULTS: Thirty-three were included (MS/NMOSD:17/16); 22 (67 %) females, mean age=35.6-years. Fifteen (46 %) had any comorbidity [MS/NMOSD:11/4], 14 physical (MS/NMOSD:10/4) and 6 psychiatric comorbidity (MS/NMOSD:5/1). Odds of any/any physical comorbidity was higher in MS versus NMOSD (age-adjusted odds ratio[aOR]=6.9;95 %CI:1.4-34.7,p=0.020/aOR=5.6;95 %:1.1-28.0,p=0.037). CONCLUSIONS: Physical comorbidity affected >2-in-5 MS/NMOSD patients and psychiatric disorders ∼1-in-5. Odds of any/any physical comorbidity were >five-fold higher in MS versus NMOSD.

Gastrointestinal conditions in the multiple sclerosis prodrome.

OBJECTIVE: To investigate gastrointestinal (GI)-related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset. METHODS: Using linked administrative and clinical data from British Columbia (1996-2013), Canada, we identified an administrative cohort via a validated algorithm (n = 6863), a clinical cohort diagnosed at a MS clinic (n = 966), and matched controls (administrative cohort: n = 31,865; clinical cohort: n = 4534). In each cohort, the 5 years before a first demyelinating event or MS symptom onset (i.e., index date) were examined. We compared rates of GI-related physician visits and risk of ≥1 GI-related dispensation between MS cases and controls using negative binomial and robust Poisson models. Sex differences were tested using interaction terms. RESULTS: The administrative cohort MS cases had higher rates of physician visits related to gastritis and duodenitis (adjusted rate/risk ratio (aRR):1.42, 95% CI: 1.10-1.83) and diseases of the esophagus (aRR: 1.46, 95% CI: 1.06-2.02) prior to the index date. MS cases also had greater risk of at least one dispensation for several drug classes, including constipation-related (aRR: 1.82, 95% CI: 1.50-2.22), antiemetics/antinauseants (aRR: 1.64, 95% CI: 1.43-1.89), and propulsives (promotility drugs; aRR: 1.62, 95% CI: 1.47-1.79). Men had a disproportionally higher relative risk for propulsives than women (aRR: men = 2.32, 95% CI: 1.79-3.00; women = 1.54, 95% CI: 1.36-1.72). Several findings were similar in the smaller clinical cohort though none reached statistical significance. INTERPRETATION: GI-related physician visits and drug dispensations were more common in the 5 years before the first demyelinating event versus matched controls. GI symptoms are a measurable feature of the prodromal or early phase of MS, with a sex difference evident.

A cross-sectional study of MRI features and the gut microbiome in pediatric-onset multiple sclerosis.

OBJECTIVE: To identify gut microbiome features associated with MRI lesion burden in persons with pediatric-onset multiple sclerosis (symptom onset <18 years). METHODS: A cross-sectional study involving the Canadian Paediatric Demyelinating Disease Network study participants. Gut microbiome features (alpha diversity, phylum- and genus-level taxa) were derived using 16S rRNA sequencing from stool samples. T1- and T2-weighted lesion volumes were measured on brain MRI obtained within 6 months of stool sample procurement. Associations between the gut microbiota and MRI metrics (cube-root-transformed) were assessed using standard and Lasso regression models. RESULTS: Thirty-four participants were included; mean ages at symptom onset and MRI were 15.1 and 19.0 years, respectively, and 79% were female. The T1- and T2-weighted lesion volumes were not significantly associated with alpha diversity (age and sex-adjusted p > 0.08). At the phylum level, high Tenericutes (relative abundance) was associated with higher T1 and T2 volumes (ß coefficient = 0.25, 0.37) and high Firmicutes, Patescibacteria or Actinobacteria with lower lesion volumes (ß coefficient = -0.30 to -0.07). At the genus level, high Ruminiclostridium, whereas low Coprococcus 3 and low Erysipelatoclostridium were associated with higher lesion volumes. INTERPRETATION: Our study characterized the gut microbiota features associated with MRI lesion burden in pediatric-onset MS, shedding light onto possible pathophysiological mechanisms.

Risk of Multiple Sclerosis in People Living with HIV: An International Cohort Study.

OBJECTIVE: There has been interest in a possible negative association between HIV and multiple sclerosis (MS). We aimed to compare the risk of MS in a cohort of individuals living with HIV to that in the general population. METHODS: Population-based health data were accessed for 2 cohorts of HIV-positive persons from Sweden and British Columbia, Canada. Incident MS was identified using MS registries or a validated algorithm applied to administrative data. Individuals with HIV were followed from 1 year after the first clinical evidence of HIV or the first date of complete administrative health data (Canada = April 1, 1992 and Sweden = January 1, 2001) until the earliest of incident MS, emigration, death, or study end (Canada = March 31, 2020 and Sweden = December 31, 2018). The observed MS incidence rate in the HIV-positive cohort was compared to the expected age-, sex-, calendar year-, income-specific, and region of birth-specific rates in a randomly selected sample of >20% of each general population. The standardized incidence ratio (SIR) for MS following the first antiretroviral therapy exposure ("ART-exposed") was also calculated. RESULTS: The combined Sweden-Canada cohort included 29,163 (75% men) HIV-positive persons. During 242,248 person-years of follow-up, 14 incident MS cases were observed in the HIV-positive cohort, whereas 26.19 cases were expected. The SIR for MS in the HIV-positive population was 0.53 (95% confidence interval [CI] = 0.32-0.90). The SIR for MS following the first ART exposure was 0.55 (95% CI = 0.31-0.96). INTERPRETATION: This international population-based study demonstrated a lower risk of MS among HIV-positive individuals, and HIV-positive ART-exposed individuals. These findings provide support for further exploration into the relationship among HIV, ART, and MS. ANN NEUROL 2024;95:487-494.

Multiple sclerosis disease-modifying drug use by immigrants: a real-world study.

Little is known about disease-modifying drug (DMD) initiation by immigrants with multiple sclerosis (MS) in countries with universal health coverage. We assessed the association between immigration status and DMD use within 5-years after the first MS-related healthcare encounter. Using health administrative data, we identified MS cases in British Columbia (BC), Canada. The index date was the first MS-related healthcare encounter (MS/demyelinating disease-related diagnosis or DMD prescription filled), and ranged from 01/January/1996 to 31/December/2012. Those included were ≥ 18 years old, BC residents for ≥ 1-year pre- and ≥ 5-years post-index date. Persons becoming permanent residents 1985-2012 were defined as immigrants, all others were long-term residents. The association between immigration status and any DMD prescription filled within 5-years post-index date (with the latest study end date being 31/December/2017) was assessed using logistic regression, reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We identified 8762 MS cases (522 were immigrants). Among immigrants of lower SES, odds of filling any DMD prescription were reduced, whereas they did not differ between immigrants and long-term residents across SES quintiles (aOR 0.96; 95%CI 0.78-1.19). Overall use (odds) of a first DMD within 5 years after the first MS-related encounter was associated with immigration status.

Psychiatric Comorbidity During the Prodromal Period in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Psychiatric morbidity is common after a multiple sclerosis (MS) diagnosis. However, little is known about psychiatric comorbidity during the prodromal phase (before MS onset). To compare the prevalence and relative burden of psychiatric morbidity in individuals with MS with matched controls before MS onset. METHODS: Using linked administrative and clinical data from British Columbia, Canada, we identified cases with MS through a validated algorithm or from neurologist-diagnosed MS clinic attendees. Cases were matched by age, sex, and geographical location with up to 5 general population controls. We identified psychiatric morbidity through a validated definition and determined its prevalence in cases/controls in the 5 years before the first demyelinating claim of cases with MS ("administrative cohort") or symptom onset ("clinical cohort") and estimated case/control prevalence ratios with 95% CIs. We also compared the yearly number of physician visits for psychiatric morbidity, visits to psychiatrists, psychiatric-related admissions, and psychotropic dispensations pre-MS onset in cases/controls regardless of whether psychiatric morbidity algorithm was fulfilled using negative binomial regression fitted through generalized estimating equations; results were reported as adjusted rate ratios with 95% CIs. We assessed yearly trends through interaction terms between cases/controls and each year pre-MS onset. RESULTS: The administrative cohort comprised 6,863/31,865 cases/controls; the clinical cohort comprised 966/4,534 cases/controls. Over the entire 5-year period pre-MS onset, 28.0% (1,920/6,863) of cases and 14.9% (4,738/31,865) of controls (administrative cohort) had psychiatric morbidity, as did 22.0% (213/966) of clinical cases and 14.1% (638/4,534) controls. Psychiatric morbidity prevalence ratios ranged from 1.58; 95% CI 1.38-1.81 (clinical cohort) to 1.91; 95% CI 1.83-2.00 (administrative cohort). In the administrative cohort, health care use was higher for cases in each year pre-MS onset (all 95% CIs >1); physician visits were 78% higher in year 5 pre-MS onset and 124% 1 year before; visits to psychiatrists were 132% higher in year 5 and 146% in year 1; hospitalizations were 129% higher in year 5 and 197% in year 1; and prescription dispensations were 72% higher in year 5 and 100% in year 1. Results were not significant in the clinical cohort. DISCUSSION: Psychiatric morbidity represents a significant burden before MS onset and may be a feature of the MS prodrome.

Etiology, effects and management of comorbidities in multiple sclerosis: recent advances.

Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens. Comorbidities exert effects throughout the disease course, from symptom onset through diagnosis to the end of life. At the individual level, comorbidity is associated with higher relapse rates, greater physical and cognitive impairments, lower health-related quality of life, and increased mortality. At the level of the health system and society, comorbidity is associated with increased health care utilization, costs and work impairment. A nascent literature suggests that MS affects outcomes from comorbidities. Comorbidity management needs to be integrated into MS care, and this would be facilitated by determining optimal models of care.

Polypharmacy and multiple sclerosis: A population-based study.

BACKGROUND: Little is known about polypharmacy and multiple sclerosis (MS). OBJECTIVES: To estimate polypharmacy prevalence in a population-based MS cohort and compare persons with/without polypharmacy. METHODS: Using administrative and pharmacy data from Canada, we estimated polypharmacy prevalence (⩾5 concurrent medications for >30 consecutive days) in MS individuals in 2017. We compared the characteristics of persons with/without polypharmacy and described the number of polypharmacy days, the most common medication classes contributing to polypharmacy and hyper-polypharmacy prevalence (⩾10 medications). RESULTS: Of 14,227 included individuals (75% women), mean age = 55.4 (standard deviation (SD): 13.2) years; 28% (n = 3995) met criteria for polypharmacy (median polypharmacy days = 273 (interquartile range (IQR): 120-345)). Odds of polypharmacy were higher for women (adjusted odds ratio (aOR) = 1.14; 95% confidence intervals (CI):1.04-1.25), older individuals (aORs 50-64 years = 2.04; 95% CI:1.84-2.26; ⩾65 years = 3.26; 95% CI: 2.92-3.63 vs. <50 years), those with more comorbidities (e.g. ⩾3 vs. none, aOR = 6.03; 95% CI: 5.05-7.22) and lower socioeconomic status (SES) (e.g. most (SES-Q1) vs. least deprived (SES-Q5) aOR = 1.64; 95% CI: 1.44-1.86). Medication classes most commonly contributing to polypharmacy were as follows: antidepressants (66% of polypharmacy days), antiepileptics (47%), and peptic ulcer drugs (41%). Antidepressants were most frequently co-prescribed with antiepileptics (34% of polypharmacy days) and peptic ulcer drugs (27%). Five percent of persons (716/14,227) experienced hyper-polypharmacy. CONCLUSION: More than one in four MS persons met criteria for polypharmacy. The odds of polypharmacy were higher for women, older persons, and those with more comorbidities, but lower SES.