High-efficacy Disease-modifying Therapies Research Articles

Switching to second line MS disease-modifying therapies is associated with decreased relapse rate.

While randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse. All persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities. 1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32-0.62, p < 0.0001). Switching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.

Real-world use of cladribine tablets (completion rates and treatment persistence) in patients with multiple sclerosis in England: The CLARENCE study

BackgroundTreatment with cladribine tablets, a high-efficacy disease-modifying therapy (DMT), has been available in England since 2017 for patients with highly active relapsing multiple sclerosis (MS). Real-world data on treatment completion, persistence and switching in patients treated with cladribine tablets are beginning to emerge, but only small single and multicentre cohorts have reported so far. This longitudinal retrospective observational study (CLARENCE) evaluated a large cohort (>1900) of patients with highly active relapsing MS, receiving cladribine tablets across England, to determine rates of treatment completion, persistence and switching in the real world. MethodsUsing data obtained from Blueteq® forms, a compulsory requirement for DMT reimbursement in England, we evaluated rates of treatment completion (defined as the proportion of patients who received the full 2-year course of cladribine tablets), treatment persistence (defined as the proportion of patients who did not switch and/or discontinue treatment before receiving the full 2-year course) and treatment switch (defined as the proportion of patients who switched treatment from cladribine tablets to another DMT at any point after their first course). The change in Expanded Disability Status Scale (EDSS) score between Years 1 and 2 of treatment was also determined. All data were analysed descriptively. ResultsBlueteq® forms were completed for 1934 MS patients treated with cladribine tablets; of these patients, 691 (36%) were treatment naïve. The median EDSS score (range) at treatment initiation with cladribine tablets was 2.5 (0, 8.5). At time of analysis (September 2021, last follow-up point), a total of 1020 (53%) patients had completed the full 2-year course of cladribine tablets. At the same time point, 1762 (91%) patients were considered as treatment persistent (i.e., the patient had completed either 1 course of tablets with <18 months of follow-up data or the full 2-year course of cladribine tablets). Overall, 78 (4%) patients switched to another DMT at any point after their first course, which included 33 (1.7%) patients who switched after completing the full 2-year course. In terms of their disability, 469 (84%) patients had stable EDSS scores between Years 1 and 2 of treatment. ConclusionIn this large real-world study of patients receiving cladribine tablets across England, high rates of treatment persistence and low rates of switching were observed, with only 1.7% of patients receiving the full 2-year course and switching treatment. The majority (84%) of evaluable patients showed stable disability between Years 1 and 2 of treatment. These findings complement earlier data from clinical trials and real-world studies, confirming the effectiveness of cladribine tablets for patients with highly active relapsing MS.

Barriers to accessing multiple sclerosis disease-modifying therapies in the Middle East and North Africa region: A regional survey-based study

BackgroundMultiple sclerosis (MS) management varies markedly between different countries of the Middle East and North Africa (MENA) region based on the availability and accessibility of disease-modifying therapies (DMTs). ObjectiveTo evaluate the accessibility to DMTs in each MENA country, identify barriers to treatment and make recommendations for improved access to DMTs across the region. MethodsThis is a descriptive, survey-based study whereby we extracted data collected, between October 2019 and April 2020, for countries in the MENA region by the Multiple Sclerosis International Federation (MSIF) through their Atlas of MS survey. Results16 out of 19 countries in the MENA region were included in this study. Sudan and Syria did not have any originator DMTs approved. Interferons were the most widely low-efficacy originator approved DMTs. Three countries did not have any high efficacy DMTs approved. Moreover, follow-on DMTs were approved in half (50%) of the countries. Cost of treatment was the most important barrier, reported in nearly half (47%) of the MENA countries. ConclusionAlthough most MENA countries have access to DMTs, more than half of countries report problems with treatment continuation, highlighting the need for a targeted regional strategy to address the variations in access to MS treatments.

Risk of breakthrough COVID-19 after vaccination among people with multiple sclerosis on disease-modifying therapies.

Disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) may decrease vaccine effectiveness. We aimed to explore the association between various DMTs and the risk for breakthrough COVID-19. Population-based data from Clalit Health Services, Israel's largest healthcare organization, were used. PwMS treated with DMTs without prior COVID-19 were followed from the commencement of the mass vaccination campaign in December 2020. The end of follow-up was at the time of COVID-19 infection, the receipt of a third vaccine dose or until the end of August 2021. Time-dependent multivariate Cox proportional hazard models were used to estimate hazard ratios for COVID-19 according to vaccination, DMT, age, gender, disability and comorbidities. 2511 PwMS treated with DMTs were included (Age: 46.2 ± 14.6, 70% Female, EDSS: 3.0 ± 2.1). Of whom, 2123 (84.5%) received 2 vaccine doses. On multivariate models that included all pwMS, vaccination was protective (HR = 0.41, P < 0.001). On multivariate models that included only fully vaccinated pwMS cladribine, ocrelizumab, S1P receptor modulators and natalizumab were associated with breakthrough COVID-19 (HR = 6.1, 4.7, 3.7 and 3.3; P = 0.004, 0.008, 0.02 and 0.05, respectively). On multivariate models that included unvaccinated and fully vaccinated pwMS on each DMT separately, a protective trend was noted for vaccination on all DMTs (0.09 < HR < 0.65), except for cladribine (HR = 1.1). This protective trend was not statistically significant on ocrelizumab, S1P receptor modulators and natalizumab. COVID-19 among pwMS was generally mild. Only 2 vaccinated pwMS had a severe infection with eventual recovery. Vaccination effectively protects pwMS from COVID-19. An increased risk of breakthrough infection was noted on high-efficacy DMTs, however COVID-19 after vaccination was usually mild.

B cell depletion therapy does not resolve chronic active multiple sclerosis lesions.

Chronic active lesions (CAL) in multiple sclerosis (MS) have been observed even in patients taking high-efficacy disease-modifying therapy, including B-cell depletion. Given that CAL are a major determinant of clinical progression, including progression independent of relapse activity (PIRA), understanding the predicted activity and real-world effects of targeting specific lymphocyte populations is critical for designing next-generation treatments to mitigate chronic inflammation in MS. We analyzed published lymphocyte single-cell transcriptomes from MS lesions and bioinformatically predicted the effects of depleting lymphocyte subpopulations (including CD20 B-cells) from CAL via gene-regulatory-network machine-learning analysis. Motivated by the results, we performed invivo MRI assessment of PRL changes in 72 adults with MS, 46 treated with anti-CD20 antibodies and 26 untreated, over ∼2 years. Although only 4.3% of lymphocytes in CAL were CD20 B-cells, their depletion is predicted to affect microglial genes involved in iron/heme metabolism, hypoxia, and antigen presentation. Invivo, tracking 202 PRL (150 treated) and 175 non-PRL (124 treated), none of the treated paramagnetic rims disappeared at follow-up, nor was there a treatment effect on PRL for lesion volume, magnetic susceptibility, or T1 time. PIRA occurred in 20% of treated patients, more frequently in those with ≥4 PRL (p=0.027). Despite predicted effects on microglia-mediated inflammatory networks in CAL and iron metabolism, anti-CD20 therapies do not fully resolve PRL after 2-year MRI follow up. Limited tissue turnover of B-cells, inefficient passage of anti-CD20 antibodies across the blood-brain-barrier, and a paucity of B-cells in CAL could explain our findings. Intramural Research Program of NINDS, NIH; NINDS grants R01NS082347 and R01NS082347; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Cariplo Foundation (grant #1677), FRRB Early Career Award (grant #1750327); Fund for Scientific Research (FNRS).

Predictive models of multiple sclerosis-related cognitive performance using routine clinical practice predictors.

The application of machine learning (ML) to predict cognitive evolution is exceptionally scarce. Computer-based self-administered cognitive tests provide the opportunity to set up large longitudinal datasets to aid in developing ML prediction models of risk for Multiple Sclerosis-related cognitive decline. to analyze to what extent clinically feasible models can be built with standard clinical practice features and subsequently used for reliable prediction of cognitive evolution. This prospective longitudinal study includes 1184 people with MS who received a Processing Speed (PS) evaluation at 12 months of follow-up measured by the iPad®-based Processing Speed Test (PST). Six of the most potent classification models built with routine clinical practice features were trained and tested to predict the 12-month patient class label (PST worsening (PSTw) versus PST stable). A rigorous scheme of all the preprocessing steps run to obtain reliable generalization performance is detailed. Based on a 12-month reduction of 10% of the PST raw score, 187/1184 (15.8%) people with MS were classified as PSTw. The trees-based models (random forest and the eXtreme Gradient Boosting) achieved the best performance, with an area under the receiver operating characteristic curve (AUC) of 0.90 and 0.89, respectively. The timing of high-efficacy disease-modifying therapies (heDMTs) was identified as one of the top importance predictors in all the models evaluated. Using trees-based machine learning models to predict individual future information processing speed deterioration in MS could become a reality in clinical practice.

Real-World Clinical and Economic Outcomes Among Persons With Multiple Sclerosis Initiating First- Versus Second- or Later-Line Treatment With Ocrelizumab.

Prior research has demonstrated that early treatment with high-efficacy disease-modifying therapies (DMTs), including ocrelizumab (OCR), can reduce relapses and delay disease progression among persons with multiple sclerosis (pwMS) compared with escalation from low-/moderate-efficacy DMTs. However, there is a lack of research examining the impact of early use of OCR on real-world clinical and economic outcomes. This study aimed to evaluate differences in events often associated with a relapse (EOAR) as well as non-DMT healthcare resource use (HCRU) and costs among pwMS who received OCR as a first-line treatment compared with later-line treatment after diagnosis. Newly diagnosed adult pwMS were selected from deidentified Optum Market Clarity claims data (study period: January 1, 2015-June 30, 2021). All pwMS were required to have initiated OCR after diagnosis and have 12months of continuous eligibility prior to diagnosis. The index date was the date of initiation of the first-line DMT after diagnosis. pwMS who initiated OCR as first-line (1L OCR cohort) or a second- or later-line treatment (2L + OCR cohort) were matched 1:1 based on length of continuous eligibility after the first-line DMT and weighted using stabilized inverse probability of treatment. In the follow-up period, differences in outcomes, including annualized EOAR, non-DMT HCRU and costs, were evaluated for pwMS in the 1L vs. 2L + OCR cohorts. The sample included 748 pwMS. During the follow-up period, pwMS in the 1L OCR cohort had a significantly lower annual rate ofEOAR compared with pwMS in the 2L + OCR cohort (0.37 vs. 0.56; difference: 0.20 [95% CI 0.08, 0.32]). pwMS in the 1L OCR cohort had a significantly lower probability of any hospitalization within 1year, fewer non-DMT outpatient visits and lower all-cause and MS-related, non-DMT costs compared with pwMS in the 2L + OCR cohort. First-line initiation OCR was associated with improvements in clinical and non-DMT economic outcomes compared with later-line initiation of OCR, suggesting that early initiation may benefit both patients and the healthcare system.

Escalation or high-efficacy disease-modifying therapies in multiple sclerosis

Escalation or high-efficacy disease-modifying therapies in multiple sclerosis

COVID-19 vaccination uptake in people with multiple sclerosis compared to the general population.

To determine the COVID-19 vaccine uptake among people with multiple sclerosis (pwMS) compared to the general population in Croatia. Data from all pwMS entered in the MS Base register until March 24th, 2022 were extracted including age, sex, MS phenotype, disease-modifying therapy (DMT), and date of COVID-19 vaccination. Data on the general population of Croatia were obtained from the vaccination register of the Croatian Institute of Public Health. 64.4% pwMS were fully COVID-19 vaccinated which was comparable to 66.3% of the general population. More pwMS were fully vaccinated in the age group 20-24 (74.1% vs 51.7%), and fewer pwMS were fully vaccinated in the age group 65-69 (33.3% vs 80.4%) compared to the general population of the same age group, respectively. PwMS who received at least one dose of any COVID-19 vaccine were older (40.5 vs 37.6years, p = 0.01), had higher EDSS (2.0 vs 1.0, p = 0.025), and had longer disease duration (6.39 vs 5.35years, p = 0.02), were more likely to have progressive disease course (p = 0.049) and were on high efficacy DMTs (p = 0.045) compared to unvaccinated pwMS. Longer disease duration positively predicted vaccine uptake. Croatia has suboptimal COVID-19 vaccination uptake without a significant difference between the general population and pwMS.

Therapy effect on AI-derived thalamic atrophy using clinical routine MRI protocol: A longitudinal, multi-center, propensity-matched multiple sclerosis study.

The effect of disease modifying therapies (DMTs) on brain atrophy in persons with multiple sclerosis (pwMS) is typically investigated in highly standardized clinical trial settings or single-center academic institutions. We aimed at utilizing artificial intelligence (AI)-based volumetric analysis on routine unstandardized T2-FLAIR scans in determining the effect of DMTs on lateral ventricular volume (LVV) and thalamic volume (TV) changes in pwMS. The DeepGRAI (Deep Gray Rating via Artificial Intelligence) registry is a multi-center, longitudinal, observational, real-word study with a convenience sample of 1002 relapsing-remitting (RR) pwMS from 30 United States sites. Brain MRI exams acquired as part of the routine clinical management were collected at baseline and on average at 2.6-years follow-up. The MRI scans were acquired either on 1.5T or 3T scanners with no prior harmonization. TV was determined using the DeepGRAI tool and lateral ventricular volume LVV was measured using NeuroSTREAM software. After propensity matching based on baseline age, disability and time of follow-up, untreated pwRRMS had significantly greater TV change when compared to treated pwRRMS (-1.2% vs. -0.3%, p=0.044). PwRRMS treated with high-efficacy DMTs had significant and two-fold lower% LVV change when compared to pwRRMS treated on moderate-efficacy DMTs (3.5% vs. 7.0%, p=0.001). PwRRMS who stopped DMT during the follow-up had significantly greater annualized% TV change compared to pwRRMS who remained on their DMT (-0.73% vs. -0.14%, p=0.012) and significantly greater annualized% LVV change (3.4% vs. 1.7%, p=0.047). These findings were also observed in a propensity analysis that additionally incorporated matching for scanner model at both baseline and follow-up visits. LVV and TV measured on T2-FLAIR scans can detect treatment-induced short-term neurodegenerative changes measured in a real-word unstandardized, multicenter, clinical routine setting.

HTA80 Cost-Effectiveness of Ocrelizumab Compared with Dmt for the Treatment of Relapsing-Remitting Multiple Sclerosis in Czech Republic

Ocrelizumab represents a generally well-tolerated, high-efficacy disease-modifying therapy (DMT) approved in Czech Republic for the RRMS. The aim of this study was to evaluate the cost-effectiveness of ocrelizumab compared with other DMT (glatiramer acetate, interferon beta-1a, interferon beta-1b, teriflunomide) for the treatment of RRMS from payer perspective.

Monoclonal Antibodies in Pregnancy and Breastfeeding in Patients with Multiple Sclerosis: A Review and an Updated Clinical Guide.

The use of high-efficacy disease-modifying therapies (DMTs) early in the course of multiple sclerosis (MS) has been shown to improve clinical outcomes and is becoming an increasingly popular treatment strategy. As a result, monoclonal antibodies, including natalizumab, alemtuzumab, ocrelizumab, ofatumumab, and ublituximab, are frequently used for the treatment of MS in women of childbearing age. To date, only limited evidence is available on the use of these DMTs in pregnancy. We aim to provide an updated overview of the mechanisms of action, risks of exposure and treatment withdrawal, and pre-conception counseling and management during pregnancy and post-partum of monoclonal antibodies in women with MS. Discussing treatment options and family planning with women of childbearing age is essential before commencing a DMT in order to make the most suitable choice for each individual patient.

The Czech National MS Registry (ReMuS): Data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021.

Multiple sclerosis treatment strategies are changing in the Czech Republic. According to data from 2013-2021, the proportion of patients starting high-efficacy disease-modifying therapies is increasing. In this survey, we describe the actual data trends in multiple sclerosis (MS) patients beginning their first disease‑modifying therapies (DMTs) from 2013 to 2021. The secondary objective was to present the history, data collection, and scientific potential of the Czech National MS registry (ReMuS). First, using descriptive statistics, we analysed the data for patients starting their first DMTs, either platform (including dimethyl fumarate) or high-efficacy DMTs (HE-DMTs), for each successive year. Second, a detailed description of the history, data collection, completeness, quality optimising procedures, and legal policies of ReMuS is provided. Based on the dataset from December 31, 2021, the total number of monitored patients with MS in ReMuS increased from 9,019 in 2013 (referred from 7 of 15 MS centres) to 12,940 in 2016 (referred from all 15 Czech MS centres) to 17,478 in 2021. In these years, the percentage of patients treated with DMTs in the registry ranged from 76 to 83%, but the proportion of patients treated with HE-DMTs changed from 16.2% in 2013 to 37.1% in 2021. During the follow-up period, a total of 8,491 treatment-naive patients received DMTs. The proportion of patients (all MS phenotypes) starting HE-DMTs increased from 2.1% in 2013 to 18.5% in 2021. Patient registries, including ReMuS, provide an essential quality data source, especially in light of the increasing percentage of patients on HE-DMTs. Although early initiation of HE-DMT can provide considerable benefits, it also carries greater potential risks. Consistent long-term follow-up of patients in real‑world clinical practice, which only registries allow, is therefore crucial to evaluate the efficacy and safety of therapeutic strategies, for epidemiological research and to assist decision making by healthcare providers and regulatory bodies.

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

Wearing-Off Effect Toward the End of Treatment Cycles in Patients With MS Receiving High-Efficacy Disease-Modifying Therapies: Data From Social Media Listening (P3-3.009)

<h3>Objective:</h3> To explore how various stakeholders (patients living with multiple sclerosis [PlwMS], caregivers [CGs], health care practitioners [HCPs], advocacy groups) describe symptoms, timing, coping strategies, and impact on quality of life (QoL) of the wearing-off effect (WOE) while receiving disease-modifying therapies (DMTs; natalizumab, ocrelizumab, ofatumumab, rituximab). <h3>Background:</h3> Symptoms such as fatigue, mobility issues, and physical pain toward the end of treatment cycles (WOE) have been reported in PlwMS receiving DMTs. Patients on social media report a QoL impact associated with WOE. <h3>Design/Methods:</h3> Publicly available posts related to WOE on social media, blogs, and forums were reviewed. WOE-specific posts authored in English by key stakeholders and posted between February 1, 2020 and February 16, 2022 were analyzed. Posts were identified through a specific search term–based funneling methodology. <h3>Results:</h3> We identified 43,834 posts related to broader MS and WOE; 730 conversations were WOE specific, with 725 authored by PlwMS or CGs. Of these 725 posts, 535 were related to experiencing WOE and 277/535 posts mentioned WOE-associated symptoms. The most commonly reported WOE durations were 2–4 weeks; fatigue was the most mentioned symptom, followed by mobility issues and physical pain. Treatment was specified in 374/535 posts; 9% of these mentioned a QoL impact, such as need for more downtime, interference with work, and difficulty walking. WOE coping strategies mentioned by patients included switching to other DMTs, reducing intervals between cycles, and taking steroids/other medications. WOE-related conversations by HCPs and advocacy groups were scarce (4 and 1 posts, respectively). <h3>Conclusions:</h3> Mentions of WOE by patients receiving DMTs and reports of WOE-related symptoms impacting QoL were common. Factors like differing DMT durations and numbers of patients receiving different DMTs make observations of social media conversations prone to an inherent bias. Further research regarding WOE and potential gaps between HCP and patient perceptions/awareness of WOE is needed. <b>Disclosure:</b> Mr. Clement has received personal compensation for serving as an employee of Novartis. Mr. Clement has stock in Roche. Joanne Fielding, 24833 has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . The institution of Joanne Fielding, 24833 has received research support from BioEye. The institution of Joanne Fielding, 24833 has received research support from Equity Trustees. The institution of Joanne Fielding, 24833 has received research support from Macquarie Group Foundation. The institution of Joanne Fielding, 24833 has received research support from Genzyme. The institution of Joanne Fielding, 24833 has received research support from Biogen. The institution of Joanne Fielding, 24833 has received research support from Open Medicines Australia. The institution of Joanne Fielding, 24833 has received research support from EyeOnVision. Ms. Serceau has nothing to disclose. Ms. Robinson has nothing to disclose. Chinmay Deshpande has received personal compensation for serving as an employee of Novartis Pharmaceutical Corporation . Chinmay Deshpande has stock in Novartis Pharmaceutical Corporation .

Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic.

The immune system plays a significant role in multiple sclerosis. While MS was historically thought to be T cell-mediated, multiple pieces of evidence now support the view that B cells are essential players in multiple sclerosis pathogenic processes. High-efficacy disease-modifying therapies that target the immune system have emerged over the past two decades. Anti-CD20 monoclonal antibodies selectively deplete CD20+ B and CD20+ T cells and efficiently suppress inflammatory disease activity. These monotherapies prevent relapses, reduce new or active magnetic resonance imaging brain lesions, and lessen disability progression in patients with relapsing multiple sclerosis. Rituximab, ocrelizumab, and ofatumumab are currently used in clinical practice, while phase III clinical trials for ublituximab have been recently completed. In this review, we compare the four anti-CD20 antibodies in terms of their mechanisms of action, routes of administration, immunological targets, and pharmacokinetic properties. A deeper understanding of the individual properties of these molecules in relation to their efficacy and safety profiles is critical for their use in clinical practice.

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

Background: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: To determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.

Trajectories of disease-modifying therapies and associated sickness absence and disability pension among 1923 people with multiple sclerosis in Sweden

There is limited information on the trajectories of disease-modifying therapy (DMT) use and their association with sickness absence and/or disability pension (SADP) among people with multiple sclerosis (PwMS). The objective of the study was to identify trajectories of DMT use over 10 years among PwMS, identify sociodemographic and clinical factors associated with the trajectories, and to assess the association between identified trajectories and SADP days. A longitudinal register-based study was conducted, on a prospective data set linked across six nationwide registers, assessing treatment courses of PwMS with DMTs for the 10 years following multiple sclerosis (MS) onset. The study included 1923 PwMS with MS onset in 2007-2010, when aged 19-56 years. In each 6-month-period, their treatment was categorized as before treatment, high-efficacy, non-high-efficacy, or no DMT. Sequence analysis was performed to identify sequences of the treatment categories and cluster them into different DMT trajectories. Cluster belonging, in relation to demographic and clinical characteristics, was assessed through log-multinomial regression analysis. The association of trajectories/cluster-belonging with SADP net days was assessed using generalized estimating equation (GEE) models. Cluster analyses identified 4 trajectories of DMT use: long-term non-high-efficacy DMTs (38.6%), escalation to high-efficacy DMTs (31.2%), delayed start and escalation to high-efficacy DMTs (15.4%), and discontinued/ no DMT (14.2%). Age, MS type, expanded disability status scale (EDSS) score and the number of DMT switches were associated with cluster belonging. The youngest age group (18-25) were more likely to be in the escalation to high-efficacy cluster. People with primary progressive MS were more likely to be in the delayed start or discontinued/ no DMT cluster. Higher EDSS scores were associated to being in the other three clusters than in the long-term non-high-efficacy DMTs cluster. Higher number of DMT switches were associated with being in the escalation to high-efficacy DMTs cluster but less likely to be in the delayed start or discontinued/ no DMT clusters. Descriptive analyses showed a trend of fewer mean SADP days among PwMS using non-high-efficacy DMT than the other clusters about 9 years after onset. PwMS in the escalation to high-efficacy and discontinued/no DMT clusters had more SADP days. PwMS in the delayed start and escalation to high-efficacy DMTs cluster, started with fewer SADP days which increased over time. SADP days adjusted through GEE models showed trends comparable with the descriptive analysis. This study described the long-term real-world trajectories of DMT use among PwMS in Sweden using sequence analysis and showed the association of the trajectories with SADP days as well as sociodemographic and clinical characteristics.

EE15 Cost-Consequence Analysis of Ofatumumab in Comparison With Other Disease-Modifying Therapies and Best Supportive Care for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada

Ofatumumab is a high-efficacy disease-modifying therapy (DMT) approved for first-line treatment of relapsing-remitting Multiple Sclerosis (RRMS) with active disease in Canada. This study evaluated the costs and consequences of ofatumumab as an initial therapy versus other first-line and second-line DMTs and best supportive care (BSC), as well the impact of delayed treatment initiation with ofatumumab.

EE143 Cost-Effectiveness of Ofatumumab Compared with Other Disease-Modifying Therapies for the Treatment of Relapsing Multiple Sclerosis in Greece

Ofatumumab is a high-efficacy disease-modifying therapy (DMT) with a favourable benefit-risk profile recently approved in Greece for the treatment of relapsing multiple sclerosis (RMS). The purpose of this study was to evaluate the cost-effectiveness of ofatumumab vs currently available DMTs (interferon b-1a and -1b, dimethyl fumarate, teriflunomide, glatiramer acetate, ocrelizumab, natalizumab, and fingolimod) for RMS patients from the Greek payer perspective.