Cost-consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada.

Aim: The costs and consequences of initial and delayed ofatumumab treatment were evaluated in relapsing-remitting multiple sclerosis with active disease in Canada. Materials & methods: A Markov cohort model was used (10-year horizon, annual cycle length, 1.5% discounting). Scenario analyses examined ofatumumab as first-line treatment versus 3 and 5 years following switch from commonly used first-line therapies. Results: Ofatumumab resulted in improvements in clinical outcomes (relapses and disease progression) and productivity (employment and full-time work), and reduction of economic burden (administration, monitoring and non-drug costs) that were comparable to other high-efficacy therapies (ocrelizumab, cladribine and natalizumab). Switching to ofatumumab earlier in the disease course may improve these outcomes. Conclusion: Results highlight the value of a high-efficacy therapy such as ofatumumab as initial treatment (i.e., first-line) in newly diagnosed relapsing-remitting multiple sclerosis patients with active disease.

Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies.

Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological strategies will translate into better outcomes. Delivery of such interventions necessitates an evolving patient-clinician dialog within the context of a multidisciplinary team.

Cost-Effectiveness Analysis of Ofatumumab for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada.

BACKGROUND: Ofatumumab is a high-efficacy disease-modifying therapy (DMT) approved for first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Canada. OBJECTIVE: The aim of this study was to evaluate the cost effectiveness of ofatumumab from a Canadian healthcare system perspective. METHODS: A Markov cohort model was run over 65 years using annual cycles, 1.5% annual discount rate, and 100% treatment discontinuation at 10 years. The British Columbia database informed natural history transition probabilities. Treatment efficacy for DMTs were sourced from a network meta-analysis. Clinical trial data were used to estimate probabilities for treatment-related adverse events. Health utilities and costs were obtained from Canadian sources (if available) and the literature. RESULTS: Among first-line indicated therapies for RRMS, ofatumumab was dominant (more effective, lower costs) over teriflunomide, interferons, dimethyl fumarate, and ocrelizumab. Compared with glatiramer acetate and best supportive care, ofatumumab resulted in incremental cost-effectiveness ratios (ICERs) of $24,189 Canadian dollars per quality-adjusted life-year (QALY) and $28,014/QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, ofatumumab had a 64.3% probability of being cost effective. Among second-line therapies (scenario analysis), ofatumumab dominated natalizumab and fingolimod and resulted in an ICER of $50,969 versus cladribine. CONCLUSIONS: Ofatumumab is cost effective against all comparators and dominant against all currently approved and reimbursed first-line DMTs for RRMS, except glatiramer acetate.

Cervical Spinal Cord Atrophy can be Accurately Quantified Using Head Images.

BACKGROUND: Spinal cord atrophy provides a clinically relevant metric for monitoring MS. However, the spinal cord is imaged far less frequently than brain due to artefacts and acquisition time, whereas MRI of the brain is routinely performed. OBJECTIVE: To validate spinal cord cross-sectional area measurements from routine 3DT1 whole-brain MRI versus those from dedicated cord MRI in healthy controls and people with MS. METHODS: We calculated cross-sectional area at C1 and C2/3 using T2*-weighted spinal cord images and 3DT1 brain images, for 28 healthy controls and 73 people with MS. Correlations for both groups were assessed between: (1) C1 and C2/3 using cord images; (2) C1 from brain and C1 from cord; and (3) C1 from brain and C2/3 from cord. RESULTS AND CONCLUSION: C1 and C2/3 from cord were strongly correlated in controls (r = 0.94, p<0.0001) and MS (r = 0.85, p<0.0001). There was strong agreement between C1 from brain and C2/3 from cord in controls (r = 0.84, p<0.0001) and MS (r = 0.81, p<0.0001). This supports the use of C1 cross-sectional area calculated from brain imaging as a surrogate for the traditional C2/3 cross-sectional area measure for spinal cord atrophy.

Multiple Sclerosis Progression Discussion Tool Usability and Usefulness in Clinical Practice: Cross-sectional, Web-Based Survey.

BACKGROUND: A digital tool, Multiple Sclerosis Progression Discussion Tool (MSProDiscuss), was developed to facilitate discussions between health care professionals (HCPs) and patients in evaluating early, subtle signs of multiple sclerosis (MS) disease progression. OBJECTIVE: The aim of this study is to report the findings on the usability and usefulness of MSProDiscuss in a real-world clinical setting. METHODS: In this cross-sectional, web-based survey, HCPs across 34 countries completed an initial individual questionnaire (comprising 7 questions on comprehensibility, usability, and usefulness after using MSProDiscuss during each patient consultation) and a final questionnaire (comprising 13 questions on comprehensibility, usability, usefulness, and integration and adoption into clinical practice to capture the HCPs' overall experience of using the tool). The responses were provided on a 5-point Likert scale. All analyses were descriptive, and no statistical comparisons were made. RESULTS: In total, 301 HCPs tested the tool in 6974 people with MS, of whom 77% (5370/6974) had relapsing-remitting MS, including those suspected to be transitioning to secondary progressive MS. The time taken to complete MSProDiscuss was reported to be in the range of 1 to 4 minutes in 97.3% (6786/6974; initial) to 98.2% (269/274; final) of the cases. In 93.54% (6524/6974; initial) to 97.1% (266/274; final) of the cases, the HCPs agreed (4 or 5 on the Likert scale) that patients were able to comprehend the questions in the tool. The HCPs were willing to use the tool again in the same patient, 90.47% (6310/6974; initial) of the cases. The HCPs reported MSProDiscuss to be useful in discussing MS symptoms and their impact on daily activities (6121/6974, 87.76% initial and 252/274, 92% final) and cognitive function (5482/6974, 78.61% initial and 271/274, 79.2% final), as well as in discussing progression in general (6102/6974, 87.49% initial and 246/274, 89.8% final). While completing the final questionnaire, 94.9% (260/274) of the HCPs agreed that the questions were similar to those asked in regular consultation, and the tool helped to better understand the impact of MS symptoms on daily activities (249/274, 90.9%) and cognitive function (220/274, 80.3%). Overall, 92% (252/274) of the HCPs reported that they would recommend MSProDiscuss to a colleague, and 85.8% (235/274) were willing to integrate it into their clinical practice. CONCLUSIONS: MSProDiscuss is a usable and useful tool to facilitate a physician-patient discussion on MS disease progression in daily clinical practice. Most of the HCPs agreed that the tool is easy to use and were willing to integrate MSProDiscuss into their daily clinical practice.

Comorbidity and persistence of disease-modifying therapy use in relapsing remitting multiple sclerosis.

BACKGROUND: Comorbidity decreases the likelihood of initiating disease-modifying therapy (DMT) for multiple sclerosis (MS). Our objective was to characterize the relationship between comorbidity and initial DMT persistence along with reasons for DMT discontinuation. METHODS: We identified individuals with relapsing remitting MS or clinically isolated syndrome starting a platform DMT (interferon-ß, glatiramer acetate, dimethyl fumarate, teriflunomide) as initial therapy in the Canadian province of Nova Scotia from 2001 to 2016. Cases were identified using a clinic database for the only clinic providing specialty MS care in a province with universal publicly-funded health care. Comorbidity was determined by linkage of MS cases to provincial health administrative data using validated case definitions for mental health disorder, hypertension, hyperlipidemia, diabetes, chronic lung disease, ischemic heart disease, epilepsy, and inflammatory bowel disease. Cox proportional hazards models explored the relationship between comorbidity, as a count or individual comorbidities, and time to discontinuation of initial DMT. Logistic regression models explored reasons for DMT discontinuation. RESULTS: Among 1464 individuals starting platform therapy as initial DMT, the median duration on first DMT was 4 years (95% CI 4 - 4). Comorbidity count (0, 1, ≥2) was not associated with time to discontinuation of initial DMT. However, the presence of a mental health disorder was associated with an increased hazard of discontinuing DMT (hazard ratio 1.22, 95% CI 1.03-1.44). Comorbidity count was not associated with discontinuation for lack of efficacy or lack of tolerability after adjusting for covariates. CONCLUSION: Individuals with mental health comorbidity may have unique challenges that affect persistence on DMT after treatment initiation.

Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis.

Importance: Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians. Objective: To determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS. Design, Setting, and Participants: In this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019. Exposures: MWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS. Main Outcomes and Measures: The association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest-the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum-were selected a priori according to their known involvement in MS-related cognitive impairment. Results: For the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Forty-eight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test (SLF, r = -0.490; 95% CI, -0.697 to -0.284; P < .001; corpus callosum, r = -0.471; 95% CI, -0.680 to -0.262; P < .001; and cingulum, r = -0.419; 95% CI, -0.634 to -0.205; P < .001), Selective Reminding Test (SLF, r = -0.444; 95% CI, -0.660 to -0.217; P < .001; corpus callosum, r = -0.411; 95% CI, -0.630 to -0.181; P = .001; and cingulum, r = -0.361; 95% CI, -0.602 to -0.130; P = .003), and Controlled Oral Word Association Test (SLF, r = -0.317; 95% CI, -0.549 to -0.078; P = .01; and cingulum, r = -0.335; 95% CI, -0.658 to -0.113; P = .006). No significant associations were found in controls. Conclusions and Relevance: This study used MWI to demonstrate that otherwise normal-appearing brain tissue is diffusely damaged in MS, and the findings suggest that myelin water measures are associated with cognitive performance. MWI offers an in vivo biomarker feasible for use in clinical trials investigating cognition, providing a means for monitoring changes in myelination and its association with symptom worsening or improvement.

Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Positive Patients in a Multi-Ethnic Canadian Cohort.

Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease is a recently described central nervous system (CNS) inflammatory disorder with phenotypic overlap with Neuromyelitis Optica Spectrum Disorder (NMOSD). NMOSD seronegative patients, and those with limited forms of the disorder, become suspects for MOG antibody-associated disease. We describe a multi-ethnic population with MOG antibody seropositivity from the University of British Columbia MS/NMO clinic. Methods: AQP4-antibody seronegative patients presenting 2005-2016 with CNS inflammatory disease suspicious for NMOSD, as well as 20 MS controls, were retrospectively tested for MOG-IgG1 antibodies by live cell-based assay at Oxford Autoimmune Neurology Diagnostic Laboratory (UK) and by a commercial fixed cell-based assay at MitogenDx (Calgary, Canada). Additional MOG seropositive cases were identified through routine clinical interaction (2016-2018) using one of these laboratories. Clinical data was reviewed retrospectively. Results: Retrospective testing identified 21 MOG seropositives (14 by live assay only, 3 by fixed assay only and 4 by both) representing 14% of the "NMOSD suspects" cohort. One multiple sclerosis (MS) control serum was MOG seropositive. Twenty additional MOG positive cases were identified prospectively. Of 42 patients (27 female), median disease onset age was 29 years (range 3-62; 9 pediatric cases), 20 (47%) were non-Caucasian, and 3 (7%) had comorbid autoimmune disease. Most common onset phenotypes were optic neuritis (23, 55%; 8 bilateral) and myelitis (9, 21%; 6 longitudinally extensive) Three of the patients in our cohort experienced cortical encephalitis; two presented with seizures. Onset was moderate-severe in 64%, but 74% had good response to initial steroid therapy. Cumulative relapse probability for the MOG positive group at 1 year was 0.428 and at 4 years was 0.628. Most had abnormal brain imaging, including cortical encephalitis and poorly demarcated subcortical and infratentorial lesions. Few "classic MS" lesions were seen. Optic nerve lesions (frequently bilateral) were long and predominantly anterior, but 5 extended to the chiasm. Spinal cord lesions were long and short, with involvement of multiple spinal regions simultaneously, including the conus medullaris. Conclusions: Our MOG seropositive patients display phenotypes similar to previous descriptions, including cortical lesions with seizures and conus medullaris involvement. Many patients relapsed, predominantly in a different CNS location from onset. Serologic data from two different cell-based antibody assays highlight the discrepancies between live and fixed testing for MOG antibodies.

Myelin Damage in Normal Appearing White Matter Contributes to Impaired Cognitive Processing Speed in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment is a core symptom in multiple sclerosis (MS). Damage to normal appearing white matter (NAWM) is likely involved. We sought to determine if greater myelin heterogeneity in NAWM is associated with decreased cognitive performance in MS. METHODS: A total of 27 participants with MS and 13 controls matched for age, sex, and education underwent myelin water imaging (MWI) from which the myelin water fraction (MWF) was calculated. Corpus callosum, superior longitudinal fasciculus, and cingulum were chosen as regions of interest (ROIs) a priori based on their involvement in MS-related cognitive impairment. Cognitive performance was assessed using the Symbol Digit Modalities Test (SDMT). Pearson ́s product moment correlations were performed to assess relationships between cognitive performance and myelin heterogeneity (variance of MWF within an ROI). RESULTS: In MS, myelin heterogeneity in all three ROIs was significantly associated with performance on the SDMT. These correlations ranged from moderate (r = -.561) to moderately strong (r = -.654) and were highly significant (P values ranged from .001 to .0002). Conversely, myelin heterogeneity was not associated with SDMT performance in controls in any ROI (P > .108). CONCLUSION: Increased myelin heterogeneity in NAWM is associated with decreased cognitive processing speed performance in MS.

Clinical Course of Relapsing Remitting Multiple Sclerosis Post-Natalizumab.

Natalizumab is an efficacious disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS), often limited by risk of progressive multifocal leukoencephalopathy. We describe the clinical course of RRMS patients switched from natalizumab to another DMT. We identified all RRMS patients treated with natalizumab ≥3 months with JC virus antibody positivity who switched to another DMT. Overall, 84 individuals switched DMT with 57 (68%) beginning fingolimod. On fingolimod, survival without a relapse was 74% (55.8-85.6%) at 36 months and survival without disease progression was 78% (62.6-87.6%) at 36 months. In conclusion, fingolimod is an effective therapy post-natalizumab.

L'évolution clinique de patients atteints de la forme cyclique de la sclérose en plaques ayant opté pour un traitement autre que celui au natalizumab. Le natalizumab est un médicament modificateur de l'évolution de la sclérose en plaques (MMSP) efficace pour le traitement de la sclérose en plaques récurrente-rémittente (SEP-RR), souvent limité par le risque de la leucoencéphalopathie multifocale progressive. Nous décrivons l'évolution clinique des patients atteints de SEP-RR qui sont passés du natalizumab à un autre MMSP. Nous avons identifié tous les patients atteints de SEP-RR ayant été traités avec le natalizumab ≥3 mois avec la positivité des anticorps anti-virus JC et ayant opté pour un autre MMSP. Globalement, 84 personnes ont changé de MMSP avec 57 (68%) ayant changé au fingolimod. Parmi les patients sous le fingolimod, la survie sans rechute était de 74% (55,8 à 85,6%) à 36 mois et la survie sans progression était de 78% (62,6 à 87,6%) à 36 mois. En conclusion, le fingolimod est une thérapie post-natalizumab efficace.

Effects of physical comorbidities on disability progression in multiple sclerosis.

OBJECTIVE: To examine the association between physical comorbidities and disability progression in multiple sclerosis (MS). METHODS: We conducted a retrospective cohort study using linked health administrative and clinical databases in 2 Canadian provinces. Participants included adults with incident MS between 1990 and 2010 who entered the cohort at their MS symptom onset date. Comorbidity status was identified with validated algorithms for health administrative data and was measured during the 1 year before study entry and throughout the study period. The outcome was the Expanded Disability Status Scale (EDSS) score as recorded at each clinic visit. We used generalized estimating equations to examine the association between physical comorbidities and EDSS scores over time, adjusting for sex, age, cohort entry year, use of disease-modifying drugs, disease course, and socioeconomic status. Meta-analyses were used to estimate overall effects across the 2 provinces. RESULTS: We identified 3,166 individuals with incident MS. Physical comorbidity was associated with disability; with each additional comorbidity, there was a mean increase in the EDSS score of 0.18 (95% confidence interval [CI] 0.09-0.28). Among specific comorbidities, the presence of ischemic heart disease (IHD) or epilepsy was associated with higher EDSS scores (IHD 0.31, 95% CI 0.01-0.61; epilepsy 0.68, 95% CI 0.11-1.26). CONCLUSIONS: Physical comorbidities are associated with an apparent increase in MS disability progression. Appropriate management of comorbidities needs to be determined to optimize outcomes.

Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis.

BACKGROUND: On the basis of encouraging preliminary results, we conducted a randomized, controlled trial to determine whether minocycline reduces the risk of conversion from a first demyelinating event (also known as a clinically isolated syndrome) to multiple sclerosis. METHODS: During the period from January 2009 through July 2013, we randomly assigned participants who had had their first demyelinating symptoms within the previous 180 days to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of multiple sclerosis was established or until 24 months after randomization, whichever came first. The primary outcome was conversion to multiple sclerosis (diagnosed on the basis of the 2005 McDonald criteria) within 6 months after randomization. Secondary outcomes included conversion to multiple sclerosis within 24 months after randomization and changes on magnetic resonance imaging (MRI) at 6 months and 24 months (change in lesion volume on T2-weighted MRI, cumulative number of new lesions enhanced on T1-weighted MRI ["enhancing lesions"], and cumulative combined number of unique lesions [new enhancing lesions on T1-weighted MRI plus new and newly enlarged lesions on T2-weighted MRI]). RESULTS: A total of 142 eligible participants underwent randomization at 12 Canadian multiple sclerosis clinics; 72 participants were assigned to the minocycline group and 70 to the placebo group. The mean age of the participants was 35.8 years, and 68.3% were women. The unadjusted risk of conversion to multiple sclerosis within 6 months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group, a difference of 27.6 percentage points (95% confidence interval [CI], 11.4 to 43.9; P=0.001). After adjustment for the number of enhancing lesions at baseline, the difference in the risk of conversion to multiple sclerosis within 6 months after randomization was 18.5 percentage points (95% CI, 3.7 to 33.3; P=0.01); the unadjusted risk difference was not significant at the 24-month secondary outcome time point (P=0.06). All secondary MRI outcomes favored minocycline over placebo at 6 months but not at 24 months. Trial withdrawals and adverse events of rash, dizziness, and dental discoloration were more frequent among participants who received minocycline than among those who received placebo. CONCLUSIONS: The risk of conversion from a clinically isolated syndrome to multiple sclerosis was significantly lower with minocycline than with placebo over 6 months but not over 24 months. (Funded by the Multiple Sclerosis Society of Canada; ClinicalTrials.gov number, NCT00666887 .).

Physical comorbidities increase the risk of psychiatric comorbidity in multiple sclerosis.

BACKGROUND: Risk factors for psychiatric comorbidity in multiple sclerosis (MS) are poorly understood. OBJECTIVE: We evaluated the association between physical comorbidity and incident depression, anxiety disorder, and bipolar disorder in a MS population relative to a matched general population cohort. METHODS: Using population-based administrative data from Alberta, Canada we identified 9624 persons with MS, and 41,194 matches. Using validated case definitions, we estimated the incidence of depression, anxiety disorder, and bipolar disorder, and their association with physical comorbidities using Cox regression, adjusting for age, sex, socioeconomic status, and index year. RESULTS: In both populations, men had a lower risk of depression and anxiety disorders than women, as did individuals who were ≥45 years versus <45 years at the index date. The risk of bipolar disorder declined with increasing age. The risks of incident depression (HR 1.92; 1.82-2.04), anxiety disorders (HR 1.52; 1.42-1.63), and bipolar disorder (HR 2.67; 2.29-3.11) were higher in the MS population than the matched population. These associations persisted essentially unchanged after adjustment for covariates including physical comorbidities. Multiple physical comorbidities were associated with psychiatric disorders in both populations. CONCLUSION: Persons with MS are at increased risk of psychiatric comorbidity generally, and some physical comorbidities are associated with additional risk.

Chronic lung disease and multiple sclerosis: Incidence, prevalence, and temporal trends.

OBJECTIVES: We aimed to estimate the incidence and prevalence of chronic lung disease (CLD), including asthma and chronic obstructive pulmonary disease, in the MS population versus a matched cohort from the general population. METHODS: We used population-based administrative data from four Canadian provinces to identify 44,452 persons with MS and 220,849 age-, sex- and geographically-matched controls aged 20 years and older. We employed a validated case definition to estimate the incidence and prevalence of CLD over the period 1995-2005, and used Poisson regression to assess temporal trends. RESULTS: In 2005, the crude incidence of CLD per 100,000 persons was 806 (95%CI: 701-911) in the MS population, and 757 in the matched population (95%CI: 712-803). In 2005, the crude prevalence of CLD was 13.5% (95%CI: 13.1-14.0%) in the MS population, and 12.4% (95%CI: 12.3-12.6%) in the matched population. Among persons aged 20-44 years, the average annual incidence of CLD was higher in the MS population than in the matched population (RR 1.15; 95%CI: 1.02-1.30), but did not differ between populations for those aged ≥45 years. The incidence of CLD was stable, but the prevalence of CLD increased 60% over the study period. CONCLUSION: CLD is relatively common in the MS population. The incidence of CLD has been stable over time, but the prevalence of CLD has increased. Among persons aged 20-44 years, CLD is more common in the MS population than in a matched population. Given the prevalence of CLD in the MS population, further attention to the effects of CLD on outcomes in MS and approaches to mitigating those effects are warranted.

Examining the effects of comorbidities on disease-modifying therapy use in multiple sclerosis.

OBJECTIVE: Comorbidities are common in multiple sclerosis (MS) and adversely affect health outcomes. However, the effect of comorbidity on treatment decisions in MS remains unknown. We aimed to examine the effects of comorbidity on initiation of injectable disease-modifying therapies (DMTs) and on the choice of the initial DMT in MS. METHODS: We conducted a retrospective observational analysis using population-based health administrative and linked clinical databases in 3 Canadian provinces. MS cases were defined as any individual with ≥3 diagnostic codes for MS. Cohort entry (index date) was the first recorded demyelinating disease-related claim. The outcomes included choice of initial first-line DMTs and time to initiating a DMT. Logistic and Cox regression models were used to examine the association between comorbidity status and study outcomes, adjusting for sex, age, year of index date, and socioeconomic status. Meta-analysis was used to estimate overall effects across the 3 provinces. RESULTS: We identified 10,698 persons with incident MS, half of whom had ≥1 comorbidities. As the total number of comorbidities increased, the likelihood of initiating a DMT decreased. Comorbid anxiety and ischemic heart disease were associated with reduced initiation of a DMT. However, patients with depression were 13% more likely to initiate a DMT compared to those without depression at the index date (adjusted hazard ratio 1.13; 95% confidence interval 1.00-1.27). CONCLUSIONS: Comorbidities are associated with treatment decisions regarding DMTs in MS. A better understanding of the effects of comorbidity on effectiveness and safety of DMTs is needed.

Balancing Early Aggression Against Risk of Progression in Multiple Sclerosis.

Multiple sclerosis is a chronic demyelinating disease characterized by focal and diffuse inflammation of the central nervous system resulting in significant physical and cognitive disabilities. Disease-modifying therapies targeting the dysfunctional immune response are most effective in the first few years after disease onset, indicating that there is a limited time window for therapy to influence the disease course. No evidence of disease activity is emerging as a new standard for treatment response and may be associated with improved long-term disability outcomes. An aggressive management strategy, including earlier use of more potent immunomodulatory agents and close monitoring of the clinical and radiologic response to treatment, is recommended to minimize early brain volume loss and slow the progression of physical and cognitive impairments in patients with relapsing-remitting multiple sclerosis.

High incidence and increasing prevalence of multiple sclerosis in British Columbia, Canada: findings from over two decades (1991-2010).

Province-wide population-based administrative health data from British Columbia (BC), Canada (population: approximately 4.5 million) were used to estimate the incidence and prevalence of multiple sclerosis (MS) and examine potential trends over time. All BC residents meeting validated health administrative case definitions for MS were identified using hospital, physician, death, and health registration files. Estimates of annual prevalence (1991-2008), and incidence (1996-2008; allowing a 5-year disease-free run-in period) were age and sex standardized to the 2001 Canadian population. Changes over time in incidence, prevalence and sex ratios were examined using Poisson and log-binomial regression. The incidence rate was stable [average: 7.8/100,000 (95 % CI 7.6, 8.1)], while the female: male ratio decreased (p = 0.045) but remained at or above 2 for all years (average 2.8:1). From 1991-2008, MS prevalence increased by 4.7 % on average per year (p < 0.001) from 78.8/100,000 (95 % CI 75.7, 82.0) to 179.9/100,000 (95 % CI 176.0, 183.8), the sex prevalence ratio increased from 2.27 to 2.78 (p < 0.001) and the peak prevalence age range increased from 45-49 to 55-59 years. MS incidence and prevalence in BC are among the highest in the world. Neither the incidence nor the incidence sex ratio increased over time. However, the prevalence and prevalence sex ratio increased significantly during the 18-year period, which may be explained by the increased peak prevalence age of MS, longer survival with MS and the greater life expectancy of women compared to men.

Evolving role of MRI in optimizing the treatment of multiple sclerosis: Canadian Consensus recommendations.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly important for the early detection of suboptimal responders to disease-modifying therapy for relapsing-remitting multiple sclerosis. Treatment response criteria are becoming more stringent with the use of composite measures, such as no evidence of disease activity (NEDA), which combines clinical and radiological measures, and NEDA-4, which includes the evaluation of brain atrophy. METHODS: The Canadian MRI Working Group of neurologists and radiologists convened to discuss the use of brain and spinal cord imaging in the assessment of relapsing-remitting multiple sclerosis patients during the treatment course. RESULTS: Nine key recommendations were developed based on published sources and expert opinion. Recommendations addressed image acquisition, use of gadolinium, MRI requisitioning by clinicians, and reporting of lesions and brain atrophy by radiologists. Routine MRI follow-ups are recommended beginning at three to six months after treatment initiation, at six to 12 months after the reference scan, and annually thereafter. The interval between scans may be altered according to clinical circumstances. CONCLUSIONS: The Canadian recommendations update the 2006 Consortium of MS Centers Consensus revised guidelines to assist physicians in their management of MS patients and to aid in treatment decision making.