Background

Cortical plaque loads in primary progressive (PP) and secondary progressive MS (SP) appear equal whereas meningeal perivascular mononuclear/lymphocytic infiltration (PMI) may be more pronounced in SP. Basal ganglia may also be a predilection site in progressive MS.

Objectives

To compare cortical and basal ganglia plaque formation and PMI in large tissue areas from clinically well-defined PP and SP patients.

Methods

Large brain sections from clinically well-described patients with PP (N=12), SP (N=14) and 11 age-matched controls were stained with HE, Luxol-fast blue and in patients additionally for proteolipid protein and CD68. T- and B-cells were confirmed in PMI’s by CD3 and CD 20 in 3 PP and 3 SP patients. We measured total plaque, microglia-rimmed slowly expanding plaque and macrophage-filled filled active plaque area loads (% of cortex or basal ganglia area), PMI densities (#/Cm² or #/Cm meningeal length) and mean PMI size. PMI’s with min. size score one had 3-4 perivascular cell rows and 20-50 cells whereas max. score six had >19 rows and >500 cells. In one PP patient, cortical slowly expanding rims were confirmed by immunofluorescence showing IgG. Expanded Disability Status Scale (EDSS) score was estimated by chart review in a blinded fashion among 20 patients (10 PP and 12SP) from whom charts were available from two time points including one within three yrs. before death. Among these, we calculated ΔEDSS/yr. before death.

Results

Tissue areas and meningeal lengths were similar in PP and SP. Both groups displayed similarly elevated cortical plaque loads and PMI densities in the cortex and meninges. However, meningeal PMI size as well as basal ganglia (6 SP vs 8 PP) plaque load and PMI density tended to be higher in SP vs PP. Meningeal PMI density correlated with total cortical plaque load while meningeal PMI size correlated with cortical slowly expanding plaque. Cortical PMI density and size correlated with active and slowly expanding (but not total) cortical plaque. PMI’s and plaque also correlated in the basal ganglia, albeit only in SP. Overall, age at death correlated negatively with PMI’s in the meninges, cortex and in the basal ganglia. Δ EDSS/yr. before death correlated with plaque load and tended to correlate with PMI’s, albeit only in the basal ganglia.

Conclusions

Perivascular immune activation in the meninges, cortex and basal ganglia may be pathogenic, driving grey matter demyelination in progressive MS.

Background

Assigning Secondary Progressive Multiple Sclerosis (SPMS) course consistently is challenging as it is based on a gradual worsening in neurological disability independent of relapses. Clinical SPMS assignment may therefore vary between registries depending on clinical practice. Consequently, a comparison of SPMS between registries would benefit from an objective definition of SPMS.

Objectives

To validate three different methods for classifying patients into Relapsing Remitting Multiple Sclerosis (RRMS) or SPMS, compared to the clinical assignment, in five European Multiple Sclerosis (MS) registries.

Methods

Data from MS registries in Czech Republic (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients), and the United Kingdom (UK) (5,086 patients) were used. Patients with either RRMS or SPMS, age ≥ 18 years at index date (date with the latest Expanded Disability Status Scale (EDSS) observation) were included. Index period was 01/2017 - 12/2019. Three EDSS centric classification methods were applied; method 1: a modified real world EXPAND criteria (Kappos, L. et al., 2018. The Lancet 391(10127), 2018), method 2: the data-derived definition from Melbourne University but without pyramidal Functional Score (Lorscheider, J. et al., 2016. Brain 139(9)), method 3: the decision tree classifier from Karolinska Institutet (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674). The classifications were compared to the clinical assignment, where sensitivity (SPMS as true positive), specificity (RRMS as true negative) and accuracy were calculated as similarity measurements.

Results

The overall classification performance (sensitivity, specificity, accuracy) among classifiable patients were; method 1: (0.47, 0.85, 0.79), method 2: (0.77, 0.87, 0.85), method 3: (0.84, 0.83, 0.84). The proportions of unclassifiable patients with each method were; method 1: 20.0%, method 2: 32.2%, method 3: 0%. Methods 2 & 3 provided a high sensitivity, specificity and accuracy, while method 1 provided high specificity but low sensitivity. Method 3 was the only method having no unclassifiable patients.

Conclusions

Our findings suggest that these methods can be used to objectively assign SPMS with a fairly high performance in different registries. The method of choice depends on the research question and to what degree unclassifiable patients are tolerable.

Background

Until recently, disease modifying treatment options for MS patients with a secondary progressive course (SPMS) were limited, leading to the common practice of off-label treatment with drugs approved for relapsing-remitting MS. We previously showed that applying objective algorithms tend to increase the proportion of SPMS in MS registries, suggesting that SPMS is under-diagnosed in clinical practice, possibly related to available treatment options.

Objectives

To compare characteristics of patients clinically assigned an RRMS course that are re-classified when an algorithm-based SPMS assignment method is applied.

Methods

Data from MS registries in the Czech Republic (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients) and the United Kingdom (5,086 patients) were used. Inclusion criteria were patients with relapsing remitting (RR)MS or SPMS with age ≥ 18 years at the beginning of the study period (1 January 2017 – 31 December 2019). In addition to clinically assigned SPMS a data-driven assignment method was applied in the form of a decision tree classifier based on age and last EDSS (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674).

Results

Across the five registries 8,372 RRMS patients were re-assigned as SPMS (Denmark: n=1,566, Czech Republic: n=1,958, Germany: n=2,906, Sweden: n=648, United Kingdom: n=1,294) increasing the overall SPMS proportion from 17% to 31%. Re-assigned patients tended be younger, were older at onset and had experienced a quicker progression to SPMS. The overall proportion of clinically assigned SPMS patients on disease modifying treatments (DMTs) was 36% but varied greatly between registries (Czech Republic: 18%, Denmark: 35%, Germany: 50%, Sweden: 40%, and the United Kingdom: 12%) whereas a higher proportion of 69% (OR=4.0, P<0.00004) were on DMTs among RRMS patients re-assigned as SPMS (Czech Republic: 71%, Denmark: 68%, Germany: 78%, Sweden: 80%, and the United Kingdom 40%).

Conclusions

SPMS patients on DMTs may be clinically mis-classified as RRMS, most likely by not being re-assigned to SPMS after conversion has occurred. This challenges the use of time to SPMS conversion as an outcome in comparative effectiveness studies using real world evidence data and argues for the use of objective classification tools in the analysis of MS patient populations.

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.

Background

There is a growing body of literature highlighting the role that wearable and mobile remote monitoring technology (RMT) can play in the assessment of Multiple Sclerosis (MS) and how it could improve clinical care and improve efficiency of research.

The Remote Assessment of Disease and Relapse in the Central Nervous System (RADAR-CNS) study is a pan-European consortium aimed to improve the management of different CNS disorders such as MS, Epilepsy or Major Depression using smartphones and wearable devices.

Most of the available data are based in small monocentric studies, however the full validation of these digital devices requires multicenter, well designed studies providing information on feasibility and acceptability.

Objectives

We aimed to describe the outcomes of the recruitment process in the Multiple Sclerosis (MS) RADAR-CNS disability and fatigue study (D&F).

Methods

The study was run in three European centers. Main eligibility criteria for D&F study were patients with relapsing-reminting or secondary progressive MS with an EDSS score between 2.0 and 6.0. Passive and active data were continuously collected through wearables (FitBit) and mobile phones (Android) and compared to the on-site visit every 3 months. The study duration is 2 years. The study sample size was 400 patients.

Results

The enrolment of the D&F study extended for a period of 18 months. We identified 4094 potential candidates (min-max 885-1789). At the end of the recruitment period, 678 (16.6%; min-max 0-24.2%) remained in the pre-screening phase. 3416 (min-max 885-1454) patients were assessed for eligibility. Out of those, 2372 (69.4%; min-max 53.3-87.1%) were excluded for not fulfilling the eligibility criteria: 1520 (64.1%; 15.0-87.1%) did not meet the EDSS score, 254 (10.7%; 0.2-49.6%) would not be suitable in the investigators opinion and 598 (25.2%; 3.0-60.3) did not have an Android. Out of the 1044 (30.6%; 12.9-46.7) eligible candidates, 644 (61.7%; 13.8-79.7%) declined to participate. A total of 400 (90-162) patients, 9.8% of the potential candidates, were enrolled into the study.

Conclusions

Our study illustrates the primary challenges in recruiting MS patients in RMT studies related to eligibility, both clinical and technological criteria, followed by reasons related to patients preferences. There is variability in the recruitment approach between centers. In future studies, developing technology for all types of phones and more attractive assessment for patients should be considered.

Background

The rapidly evolving therapeutic landscape of multiple sclerosis (MS) can make treatment decisions challenging. Novel tools using artificial intelligence (AI) can provide estimations of MS disease progression, which may aid MS therapeutic decisions. However, whether neurologists are willing to utilize information provided by AI-based models when making therapeutic decisions is unknown.

Objectives

To assess whether neurologists rely on clinical judgment (CJ) or quantitative/ qualitative estimations of disease progression provided by hypothetical AI-based models (assuming these models can reliably identify patients at high vs. low risk of disease progression) in simulated MS case scenarios.

Methods

Overall, 231 neurologists with expertise in MS from 20 countries were randomized to receive qualitative (high/low) or quantitative (85-90% vs. 15-20%) information regarding the likelihood of disease progression. Participants were presented with simulated MS case scenarios, and initially made 7 treatment decisions based on the clinical information using CJ. After randomization, participants made 10 treatment decisions using CJ and estimations of disease progression provided by AI models. We evaluated concordance and discordance of therapeutic decisions based on CJ and AI. The primary outcome was the proportion of “optimal” treatment decisions defined as treatment escalation when there was evidence of disease progression or continuing the same treatment when clinically stable. Mixed models were used to determine the effect of randomization group, case risk level, and CJ/AI. Clinicaltrials.gov #NCT04035720

Results

Of 300 neurologists invited to participate, 231 (77.0%) completed the study. Study participants had a mean age (SD) of 44 (±10) years. Of 2310 responses, 1702 (73.7%) were classified as optimal. Optimal decisions were more common for the high-risk vs. low-risk CJ group (84.5% vs 57.6%; p<0.001). There were no differences in the estimated odds of optimal responses between the quantitative vs. qualitative groups (OR 1.09; 95%CI 0.86, 1.39) after adjustment for pre-intervention responses. The estimated odds of optimal decisions for the high-risk vs low-risk CJ group was 2.96 (95%CI: 2.47, 3.56 ) after adjusting for group, pre-intervention responses, and AI-based estimations. For low-risk CJ cases, additional input by AI-based estimations was associated with a lower likelihood of optimal responses; being worse for high-risk vs. low-risk AI estimations (OR 0.235; 95%CI: 0.16, 0.340) adjusting for covariables.

Conclusions

Neurologists were more likely to make optimal treatment choices for high-risk simulated scenarios. The addition of hypothetical information provided by AI-based models- did not improve treatment decisions for low-risk cases. These results provide a framework for understanding therapeutic decision-making in MS neurologists, who are more reliant on their own CJ over AI-based tools.

Background

Therapeutic inertia (TI) is a worldwide phenomenon affecting physicians who manage patients with chronic conditions. Previous studies in Multiple Sclerosis (MS) showed TI affects 60 to 90% of neurologists and up to 25% of daily treatment decisions.

Objectives

To determine the most important factors and levels of attributes associated with treatment escalation in an international sample of neurologists with expertise in the management of patients with MS.

Methods

We conducted an international study comprised of 300 neurologists with expertise in MS from 20 countries (Europe: 59.4%, Asia/Australia: 18.3%, America: 22.3%). Participants were presented with 12 pairs of simulated MS patient profiles reflective of case scenarios encountered in clinical practice. Patient profiles included information on age, sex, previous MS history of relapses, MRI findings, desire for pregnancy, and other relevant details. We used disaggregated discrete choice experiments (a conjoint analysis), which is a standard technique used in economic research to estimate the weight of factors and attributes (e.g. categories) affecting physicians’ decisions when considering treatment selection by asking respondents to choose between pairs of options. In our study, participants were asked to select the ideal candidate (Patient A, B or neither) for treatment escalation (from first-line to second-line therapies- eg. Fingolimod, Cladribine, Monoclonal antibodies).

Results

Of 300 neurologists invited to participate, 229 (76.3%) completed the study. The mean age (SD) of study participants was 44 (±10) years. The mean (SD) number of MS patients seen per week by each neurologist was 18 (±16).

The top 3 factors (relative importance) associated with treatment escalation were: previous relapses (20%), EDSS (18%), and MRI activity (13%). Patient demographics and desire for pregnancy had a modest influence (<3%) in treatment escalation.

Participants were 13% less likely to escalate treatment for patients with EDSS >7.0 (compared to EDSS <6.0), whereas symptom severity during most recent relapse and higher number of MRI lesions at 1 year were each associated with 6% higher likelihood of treatment escalation.

We observed differences in the weight of factors associated with treatment escalation between MS specialists and non-specialists and participants practicing in European vs. non-European countries.

Conclusions

This is the first study applying a conjoint design to assess factors associated with treatment escalation and therapeutic inertia in neurologists caring for people living with MS. Our results provide critical information on factors influencing neurologists’ treatment decisions and should be applied to continuing medical education strategies.

Background

Secondary progressive MS (SPMS) is a research area that is attracting more attention as better treatment options are still needed for this patient group. The assignment of SPMS by clinicians can differ between countries and may be influenced by drug prescription guidelines, reimbursement issues and other societal limitations.

Objectives

To compare the clinically assigned SPMS proportion to three objective SPMS classification methods in five MS registries.

Methods

Data from MS registries in the Czech Republic (CR) (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients) and the United Kingdom (UK) (5,086 patients) were used. Inclusion criteria were patients with relapsing remitting (RR)MS or SPMS with age ≥ 18 years at the beginning of the index period (1 January 2017 – 31 December 2019). In addition to clinically assigned SPMS three different classification methods were applied; method 1: modified real world EXPAND criteria (Kappos et al, Lancet 2018:391; 1263-1273), method 2: the data-derived definition from Melbourne University without the pyramidal Functional Systems Score (Lorscheider et al, Brain 2016:139; 2395-2405) and method 3: the decision tree classifier from Karolinska Institutet (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674).

Results

The SPMS proportions per registry, when comparing the clinically assigned SPMS with the results of the three classification methods, were CR: 8.8%, 21.3%, 22.1%, 25.0%; Denmark: 15.5%, 27.5%, 25.4%, 28.0%; Germany: 15.6%, 15.4%, 16.7%, 25.4%; Sweden: 23.7%, 20.8%, 23.2%, 24.6% and UK: 34.3%, 21.7%, 38.4%, 58.3% for clinical SPMS and methods 1, 2 and 3, respectively.

Conclusions

The proportion of clinically assigned SPMS patients varies between MS registries. When applying other classification methods, the SPMS proportion generally increases but remains variable between registries. As some of the classification methods have extensive requirements regarding data density, the number of unclassifiable samples created are considerable for some of the registries, which will influence the results. Providing a classification method that depends on objective information could prove useful when attempting to estimate the proportion of SPMS patients in MS populations but the choice of method may depend on the data characteristics of the individual MS registry.

Background

Ocrelizumab (OCR) is a humanized monoclonal antibody targeting CD20-positive B cells. In Denmark, OCR treatment is recommended for patients with highly active relapsing-remitting multiple sclerosis (RRMS) or with early active primary progressive MS (PPMS) and moderate disability.

Objectives

To describe the real-world experience of patients initiating OCR by characterizing baseline demographic and disease attributes, as well as treatment outcomes, of an unselected adult MS population.

Methods

Observational cohort study with prospectively enrolled cases from January 2018 to April 2020 using data from the near complete nationwide population-based Danish Multiple Sclerosis Registry.

Results

Of the 851 patients initiating OCR treatment, 735 (86%) had RRMS, 61 (7%) had secondary progressive MS (SPMS) and 55 (7%) had PPMS. Of all patients, 131 were treatment naïve and, of these, 41 were PPMS. Median disease duration in years was 10.1 for RRMS (IQR 4.4-16.7), 17.8 for SPMS (13.3-24) and 3.9 for PPMS (2.5-7.8). Median baseline Expanded Disability Status Scale (EDSS) score was 3 for RRMS (IQR 2-4), 6 for SPMS (4.5-6.5) and 3.5 for PPMS (2.5-4.5). In the year prior to OCR initiation, 50% of the RRMS population had at least one relapse on another disease-modifying therapy (DMT); of these, 58% were on high efficacy DMT. Compared to RRMS, SPMS patients were older, had higher EDSS, and 34% had at least one relapse in the two years prior to OCR start. Fifty-five (90%) were previously treated with DMT, and 69% were on DMT in the year before OCR start.

The median OCR therapy duration was 0.9 years. During follow-up, 93% of all patients were relapse-free, and five patients reported more than one relapse. Out of 18 treatment discontinuations that occurred, two were due to disease breakthrough and nine were due to adverse events. Of the 383 patients with an EDSS score between 6 and 12 months, 80 (21%) showed EDSS improvement, 266 (69%) remained stable, and 37 (10%) experienced worsening. Of the 63 reported adverse events, the most common were upper respiratory tract infections (15), allergic reactions (7), and herpes simplex infections (6).

Conclusions

In this nationwide study, we present all Danish patients receiving OCR therapy in a real-world setting. Patient characteristics differed for RRMS, PPMS and particularly the SPMS group. With reservations for the short follow-up time, 93% of all patients were relapse-free and only 10% experienced disability worsening.

Background

In primary progressive MS (PP), brain plaques are smaller and remyelinate better than in secondary progressive MS (SP) yet prognosis and response to systemic immunotherapy in PP is poor.

Objectives

To investigate relations between inflammation and myelin injury in PP vs SP and find correlates of clinical progression.

Methods

Large brain sections from clinically well-described post-mortem cohorts (12 PP, 14 SP and 11 controls) were stained with HE and Luxol-fast blue (myelin). Patients were additionally stained for proteolipid protein and CD68. We measured area loads of total plaque, microglia-rimmed slowly expanding plaque and macrophage-filled filled active plaque (% of WM area). Myelin density in the white matter overall, the normally appearing (NAWM), and the diffusely injured white matter (DIWM) was assessed by densitometry in ImageJ. In white matter compartments, we measured the density and mean size of perivascular mononuclear infiltrates (PMI; #/Cm²). The minimal PMI (grade one) had 3-4 perivascular cell rows and 20-50 cells whereas max. grade six had >19 rows and >500 cells. T- and B-cells in PMI’s were confirmed by CD3 and CD20. EDSS was estimated by chart review in a blinded fashion among 20 patients (10 PP and 12SP) from whom charts were available from two time points including one within three yrs. before death. Among these, we calculated Δ EDSS/yr before death.

In parallel, in-vivo cohorts (26 PP, 26 SP and 24 controls) were analyzed for MRI lesions with/without Gadolinium-enhancement and cerebrospinal fluid (CSF)-biomarkers of demyelination (MBP), axonal damage (NFL) and inflammation.

Results

Densities and sizes of PMI’s in NAWM as well as CSF-markers of inflammation (e.g. IgG-indices, CXCL13, MMP9) were equally increased in PP and SP and equally large PMI’s located to periventricular zones (median gr 1,8 IQR 1,5-2,1). Active and total lesion formation were higher in SP than in PP in both post-mortem and in-vivo cohorts and (post-mortem) juxtacortical and meningeal PMI’s were larger in SP than PP. By contrast, more DIWM-pathology was found in PPMS than in SPMS. The overall myelin density (post-mortem) and NAWM magnetic-transfer-ratio (in-vivo) were equally reduced while MBP and NFL levels in the CSF (in-vivo) were equally increased in both groups.

Plaque-distant (NAWM/DIWM) PMI-density (post-mortem cohort) and CSF-inflammation (in-vivo cohort) correlated with active lesion formation in SP, but not in PP. PMI-density and size in NAWM and in the white matter overall correlated with shorter survival. PMI-density in the white matter overall also correlated with slowly exp. plaque load, which in turn, correlated with Δ EDSS/yr before death in PP and in SP.

Conclusions

Perivascular inflammation is pathogenic and may contribute to white matter demyelination in PP and SP. Inflammatory demyelination in the white matter may not differ greatly but may be more diffuse and less focal in PP compared to SP.

Background

Ocrelizumab (OCR) is a humanized monoclonal antibody targeting CD20-positive B cells. In Denmark, OCR treatment is recommended for patients with highly active relapsing-remitting multiple sclerosis (RRMS) or with early active primary progressive MS (PPMS) and moderate disability.

Objectives

To describe the real-world experience of patients initiating OCR by characterizing baseline demographic and disease attributes, as well as treatment outcomes, of an unselected adult MS population.

Methods

Observational cohort study with prospectively enrolled cases from January 2018 to April 2020 using data from the near complete nationwide population-based Danish Multiple Sclerosis Registry.

Results

Of the 851 patients initiating OCR treatment, 735 (86%) had RRMS, 61 (7%) had secondary progressive MS (SPMS) and 55 (7%) had PPMS. Of all patients, 131 were treatment naïve and, of these, 41 were PPMS. Median disease duration in years was 10.1 for RRMS (IQR 4.4-16.7), 17.8 for SPMS (13.3-24) and 3.9 for PPMS (2.5-7.8). Median baseline Expanded Disability Status Scale (EDSS) score was 3 for RRMS (IQR 2-4), 6 for SPMS (4.5-6.5) and 3.5 for PPMS (2.5-4.5). In the year prior to OCR initiation, 50% of the RRMS population had at least one relapse on another disease-modifying therapy (DMT); of these, 58% were on high efficacy DMT. Compared to RRMS, SPMS patients were older, had higher EDSS, and 34% had at least one relapse in the two years prior to OCR start. Fifty-five (90%) were previously treated with DMT, and 69% were on DMT in the year before OCR start.

The median OCR therapy duration was 0.9 years. During follow-up, 93% of all patients were relapse-free, and five patients reported more than one relapse. Out of 18 treatment discontinuations that occurred, two were due to disease breakthrough and nine were due to adverse events. Of the 383 patients with an EDSS score between 6 and 12 months, 80 (21%) showed EDSS improvement, 266 (69%) remained stable, and 37 (10%) experienced worsening. Of the 63 reported adverse events, the most common were upper respiratory tract infections (15), allergic reactions (7), and herpes simplex infections (6).

Conclusions

In this nationwide study, we present all Danish patients receiving OCR therapy in a real-world setting. Patient characteristics differed for RRMS, PPMS and particularly the SPMS group. With reservations for the short follow-up time, 93% of all patients were relapse-free and only 10% experienced disability worsening.