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In patients with multiple sclerosis (MS), infections represent a significant concern, particularly given the immunomodulatory effects of disease-modifying agents (DMAs). High-efficacy DMAs (heDMAs) play a pivotal role in delaying MS progression, yet their use also raises concerns regarding the risk of infection. This study aimed to compare the infection risk with the use of heDMA and moderate-efficacy disease-modifying agents (meDMAs) in MS patients. This retrospective cohort study involved adult (18-64 years) MS patients with incident DMA use based on the 2015-2019 MarketScan Commercial Claims and Encounters Database. Patients initiating heDMAs (natalizumab, alemtuzumab, and ocrelizumab) or meDMAs (interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and glatiramer acetate) were included. The outcomes of interest were comparative risk of overall infection, serious infection, and frequently reported types of infection. Adjusted hazard ratios (aHR) were estimated in inverse probability treatment weighting (IPTW) based on Cox proportional hazard models. Among 10,003 eligible incident DMA users, 22.92% of patients initiated heDMAs. The IPTW-CPH model revealed that patients with heDMAs were associated with a higher risk of serious infection (aHR: 1.24, 95% confidence interval (CI): 1.06-1.44) and urinary tract infection (UTI; aHR: 1.21, 95% CI: 1.14-1.30). Sensitivity analyses with different follow-up periods yielded consistent findings with the main analyses. In MS, heDMAs were associated with a greater risk of serious infection and UTI compared with meDMAs. These findings suggest the need to carefully monitor and manage the infection risk to optimize the use of heDMAs in MS., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Objective: The optimal treatment strategy for the management of multiple sclerosis is widely discussed due to the increasing availability of high-efficacy disease-modifying agents (heDMAs). This study evaluated the comparative effectiveness of heDMA and moderate-efficacy disease-modifying agents (meDMAs) use in reducing annualized relapse rate (ARR) among multiple sclerosis patients., Methods: A retrospective cohort study was conducted using the 2015-2019 United States Merative MarketScan Commercial Claims Data. Adult (18-64 years) patients with incident disease-modifying agents (DMA) use were included. Claim-based relapse algorithms were applied to measure relapse events. The inverse probability treatment weighting (IPTW) based negative binomial regression model with the offset of the follow-up period was used to compare the ARR. The moderation effect of sex on ARR was also examined., Results: This study included 10,003 incident DMA users, with 22.9 % initiated heDMAs. The average ARR during follow-up among heDMA users was lower than meDMA users (0.25 vs. 0.28, p < 0.01). The IPTW-based regression found that sex moderated the relationship between the types of DMAs and ARR. Stratified analyses revealed that heDMAs were associated with a lower ARR in males (adjusted incidence rate ratio [aIRR] 0.74; 95 % confidence interval [CI] 0.59-0.94) compared with meDMAs. No significant differences were noted among females (aIRR 0.99; 95 % CI: 0.88-1.21)., Conclusion: The study found that sex moderated the effect of heDMAs, with male multiple sclerosis patients using heDMAs associated with a 26 % decreased risk of relapse than those with meDMAs. However, there was no difference in comparative effectiveness for females., Competing Interests: Declaration of competing interest Dr. Aparasu has received research funding from Astellas Inc., Incyte Corp., Gilead, and Novartis Inc. for projects unrelated to the current work. Dr. Hutton reports grants from Biogen, Novartis, MedImmune, Hoffman-LaRoche, E.M.D. Serono, Sanofi, and personal fees from Novartis, Sanofi, and Celgene outside the submitted work. The other authors declare no conflicts of interest for this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: With multiple treatment options, choosing the initial disease-modifying agent (DMA) could be crucial to managing multiple sclerosis (MS). Common treatment strategies recommend starting patients with moderate-efficacy disease-modifying agents (meDMAs), while others advocate initiating high-efficacy disease-modifying agents (heDMAs). However, limited real-world evidence exists regarding the factors associated with utilizing differing treatment strategies in the MS., Objective: This study evaluated the factors associated with the initiation of heDMAs in comparison to meDMAs among patients with MS., Methods: A retrospective cohort study was conducted using the Merative MarketScan Commercial Claims Database. Adult (18-64 years) MS patients with ≥1 DMA prescription were identified from 2016 to 2019. Patients were classified as incident heDMA or meDMA users based on their earliest DMA prescription, with a 12-month washout period. All covariates were measured during the 12-month baseline before the index DMA date. A multivariable logistic regression model, guided by the Andersen Behavioral Model, was applied to examine the predisposing, enabling, and need factors associated with using heDMAs over meDMAs., Results: There were 10,003 eligible MS patients, with the majority of users being female (74.92 %), middle-aged adults (35-54 years, 58.97 %), and enrolled in the Preferred Provider Organization (PPO, 53.10 %) healthcare plan. Overall, 2293 (22.92 %) MS patients initiated heDMAs. The multivariable logistic regression model revealed that male patients (adjusted odds ratio [aOR]: 1.46, 95 % Confidence Interval [CI]: 1.30-1.64) had higher odds of initiating heDMAs. Meanwhile, patients with bladder dysfunction medications (aOR: 1.39, 95% CI: 1.21-1.61), fatigue medications (aOR: 1.77, 95 %CI: 1.44-2.17), and impaired walking (aOR: 1.62, 95 %CI: 1.42-1.86) were more likely to initiate treatment with heDMAs. In contrast, patients with higher Elixhauser comorbidities scores, sensory symptoms (aOR: 0.47, 95 %CI: 0.42-0.53), visual symptoms (aOR: 0.63, 95 %CI: 0.54-0.73), and brainstem symptoms (aOR: 0.81, 95 %CI: 0.67-0.97) were less likely to be prescribed with heDMAs., Conclusion: The study found that approximately one in four MS patients initiated heDMAs. Both demographic and clinical factors influenced the selection of heDMA. More work is needed to understand the differential value of selecting heDMAs over meDMAs for personalizing DMA treatment., Competing Interests: Declaration of competing interest Dr. Aparasu has received research funding from Astellas Inc., Incyte Corp., Gilead, and Novartis Inc. for projects unrelated to the current work. Dr. Hutton reports grants from Biogen, Novartis, MedImmune, Hoffman-LaRoche, E.M.D. Serono, Sanofi, and personal fees from Novartis, Sanofi, and Celgene outside the submitted work. Dr. Varisco reports personal fees from Healix Infusion Therapy. The other authors declare no conflicts of interest for this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) may have a monophasic or relapsing disease course. To date, factors that may predict a relapsing disease course remain largely unknown and only limited data exist regarding the efficacy of different utilized immunotherapy regimens at preventing or reducing relapses., Objectives: To assess the characteristics, predictors, and immunotherapy of relapsing MOGAD., Methods: This multicenter retrospective analysis included all MOGAD cases at the University of Florida, Baylor College of Medicine and the University of California San Diego with minimum follow-up time of 6 months. Cox proportional hazards regression analyses, corrected for age and sex, were performed to evaluate hazard ratios (HR) of predictors of a relapsing disease course and to compare relapse hazards for utilized immunotherapies., Results: The majority of included participants (51/79 [64.6 %]) had a relapsing course, and of these individuals, 68.6 % (35/51) experienced their first relapse within the first year. However, 10/51 (19.6 %) participants experienced their first relapse ≥5 years (5-15 years) after the initial presentation. Predictors of a relapsing course were CSF pleocytosis (>150 cells/mm 3 ; HR 3.3 [1.18 - 9.24]; p = 0.023), a pediatric disease onset at age < 9 years (HR 2.69 [1.07-6.75]; p = 0.035), and an initial presentation with the clinical syndrome of meningoencephalitis (HR 3.42 [1.28 - 9.17]; p = 0.015),. In participants with a relapsing course, 13/24 (54.2 %) patients remained relapse-free on rituximab, 4/8 (50 %) on mycophenolate mofetil, and 11/14 (78.6 %) on scheduled immunoglobulins. Patients treated with immunoglobulins had significantly fewer relapses compared to patients treated with other immunotherapies (HR: 0.1 [0.2 - 0.63]; p = 0.014)., Conclusions: In our cohort, the majority of MOGAD patients relapsed. The initial relapse occurred most frequently within the first year, but first relapses also took place over a decade after the initial presentation. Prepubertal onset, severe CSF pleocytosis, and the clinical syndrome of meningoencephalitis may be predictors of a relapsing course. Of the currently available off-label steroid-sparing treatments, scheduled immunoglobulins may be the most effective in relapse prevention., Competing Interests: Declaration of competing interest Dr. Rempe received grant funding from the National Multiple Sclerosis Society. He served on advisory boards for Genentech, Sanofi-Genzyme, Alexion, and Amgen. He receives contract research support from EMD Serono, Genentech, Sanofi-Genzyme, Celgene, and Novartis. Dr. Elfasi has nothing to disclose. Dr. Alkabie has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Montalvo served on an advisory board for Horizon Therapeutics. Dr. Castrodad-Molina has no disclosures. Dr. Cuascut reports participation in scientific advisory boards for Horizon, Biogen, and Novartis as well as receiving speaker fees from Biogen. Dr. Hutton reports participation in scientific advisory boards for Novartis, Genentech, Genzyme, Bristol Myers Squibb, and Autoimmunity Biologic Solution, Inc and has also received research funding/commercial entities from Genzyme, Biogen, Novartis, Hoffmann La Roche, and MedImmune. Dr. Kinkel has received honoraria for non-promotional educational activity from Biogen and received speaker fees from Alexion, Biogen, BMS, Genentech and Sanofi-Genzyme. Dr. Graves has received research support from NMSS, Octave, Biogen, EMD Serono, Novartis, ATARA Biotherapeutics, and ABM. She has served on an advisory board for TG therapeutics and a pediatric clinical trial steering committee for Novartis. She has consulted for Google., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Real-world effectiveness can vary across oral disease-modifying agents (DMAs) and their adherence trajectories in patients with multiple sclerosis (MS). However, previous studies have not considered longitudinal adherence patterns while evaluating oral DMAs., Objectives: This study aimed to evaluate the association of oral DMAs and their adherence trajectories with annualized relapse rate (ARR) in patients with MS., Methods: This retrospective observational cohort study based on the 2015-2019 MarketScan Commercial Claims and Encounters Database involved continuous enrolled adults (18-64 years) with ≥1 MS diagnosis (ICD-9/10-CM:340/G35) and ≥ 1 oral DMA prescription. Patients were grouped into incident fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users based on the index DMA with a one-year washout period. Annual DMA adherence trajectories based on the monthly Proportion of Days Covered (PDC) one year after treatment initiation were identified using Group-Based Trajectory Modeling (GBTM). The validated claims-based ARR was evaluated during the one-year follow-up period using generalized boosted model-based inverse probability treatment weights with negative binomial regression model., Results: The study cohort consisted of 994 MS patients who initiated with FIN (23.0%), TER (22.3%), and DMF (54.7%) during the study period. GBTM grouped eligible patients into three adherence trajectories: complete adherers (59.2%), slow decliners (23.8%), and rapid decliners (17.0%). The proportion of complete adherers varied across the oral DMAs (FIN: 67.1%, TER: 55.4%, and DMF: 57.4%). The negative binomial regression modeling revealed that, while there was no difference in ARR across the three DMAs, rapid decliners (adjusted incidence rate ratio[aIRR]: 1.6, 95% CI: 1.1-2.4) had a higher rate of relapses compared to completely adherent patients. The type of oral DMAs did not moderate the relationship between ARR and the adherence trajectory groups., Conclusions: Adherence trajectories classified as rapid decliners were associated with a higher ARR than complete adherers after adjusting for their type of oral DMAs. Longitudinal medication adherence patterns are critical in reducing relapse rates in MS., Competing Interests: Declaration of competing interest Dr. Aparasu has received research funding from Astellas Inc., Incyte Corp., Gilead, and Novartis Inc. for projects unrelated to the current work. Dr. Hutton reports grants from Biogen, Novartis, MedImmune, Hoffman-LaRoche, E.M.D. Serono, Sanofi, and personal fees from Novartis, Sanofi, and Celgene outside the submitted work. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patients with multiple sclerosis (MS) frequently switch their Disease-Modifying Agents (DMA) for effectiveness and safety concerns. This study aimed to develop and compare the random forest (RF) machine learning (ML) model with the logistic regression (LR) model for predicting DMA switching among MS patients., Methods: This retrospective longitudinal study used the TriNetX data from a federated electronic medical records (EMR) network. Between September 2010 and May 2017, adults (aged ≥18) MS patients with ≥1 DMA prescription were identified, and the earliest DMA date was assigned as the index date. Patients prescribed any DMAs different from their index DMAs were considered as treatment switch. . The RF and LR models were built with 72 baseline characteristics and trained with 70% of the randomly split data after up-sampling. Area Under the Curves (AUC), accuracy, recall, G-measure, and F-1 score were used to evaluate the model performance., Results: In this study, 7258 MS patients with ≥1 DMA were identified. Within two years, 16% of MS patients switched to a different DMA. The RF model obtained significantly better discrimination than the LR model (AUC = 0.65 vs. 0.63, p  < 0.0001); however, the RF model had a similar predictive performance to the LR model with respect to F- and G-measures (RF: 72% and 73% vs. LR: 72% and 73%, respectively). The most influential features identified from the RF model were age, type of index medication, and year of index., Conclusions: Compared to the LR model, RF performed better in predicting DMA switch in MS patients based on AUC measures; however, judged by F- and G-measures, the RF model performed similarly to LR. Further research is needed to understand the role of ML techniques in predicting treatment outcomes for the decision-making process to achieve optimal treatment goals., Competing Interests: Dr. Aparasu has received research funding from Astellas Inc., Incyte Corp., Gilead, and Novartis Inc. for projects unrelated to the current work. Dr. Hutton reports grants from Biogen, Novartis, MedImmune, Hoffman-LaRoche, E.M.D. Serono, Sanofi, and personal fees from Novartis, Sanofi, Celgene outside the submitted work. The other authors declare no conflicts of interest for this article., (© 2023 The Author(s).)

Study Objective: This study compared the adherence trajectories of fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users with multiple sclerosis (MS) as there is limited evidence regarding the comparative adherence patterns of different oral disease-modifying agents (DMAs)., Design: A retrospective cohort study DATA SOURCE: 2015-2019 IBM MarketScan Commercial Claims Database., Patients: Adults (≥18 years) with MS (International Classification of Diseases [ICD]-9/10-Clinical Modification [CM]:340/G35) diagnosis and ≥1 DMA prescription., Intervention: Incident FIN-, TER-, or DMF use based on the index DMA with 1 year of washout period., Measurements: The DMA adherence trajectories based on the proportion of days covered (PDC) were examined using the Group-Based Trajectory Modeling (GBTM) one year after the treatment initiation. Generalized boosting models (GBM)-based inverse probability treatment weights (IPTW) were incorporated in multinomial logistic regression to assess the comparative adherence trajectories across oral DMAs with FIN group as a reference category., Measurements and Main Results: The study cohort consisted of 1913 patients with MS who were initiated with FIN (24.2%, n = 462), TER (24.0%, n = 458), and DMF (51.9%, n = 993) during 2016-2018. The adherence rate (PDC ≥ 0.8) among FIN, TER, and DMF users was found to be 70.8% (n = 327), 59.6% (n = 273), and 61.0% (n = 606), respectively. The GBTM grouped patients into three adherence trajectories: Complete Adherers-59.1%, Slow Decliners-22.6%, and Rapid Discontinuers-18.3%. The multinomial logistic regression model involving GBM-based IPTW revealed that DMF (adjusted odds ratio [aOR]: 2.32, 95% confidence interval [CI]:1.57-3.42) and TER (aOR: 2.50, 95% CI: 1.62-3.88) users had higher odds to be rapid discontinuers relative to FIN users. In addition, TER users were more likely (aOR: 1.50, 95% CI: 1.06-2.13) to be slow decliners compared with FIN users., Conclusion: Teriflunomide and DMF were associated with poorer adherence trajectories than FIN. More research is needed to evaluate the clinical implications of these adherence trajectories of oral DMAs to optimize the management of MS., (© 2023 Pharmacotherapy Publications, Inc.)

Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents to understanding the role of unique constellations of social determinants of health. A growing body of literature involving persons of historically underrepresented races and ethnicities in the field of multiple sclerosis is assembling. Our purpose in this narrative review is to highlight two populations in the United States: Black and Hispanic persons with multiple sclerosis. We will review the current understanding about the patterns of disease presentation, genetic considerations, response to treatment, roles of social determinants of health, and healthcare utilization. In addition, we explore future directions of inquiry as well as practical methods of meeting these challenges.

Multiple sclerosis (MS) is the most prevalent nontraumatic disabling neurologic condition among young adults worldwide. The diagnosis and management of MS is complex. The goal of this review is to provide an updated and practical approach to the diagnosis and treatment approaches in MS, emphasizing current understanding of immunopathogenesis, recent advances, and future directions, for both MS and non-MS clinicians., Competing Interests: Disclosure C.A. Pérez received postgraduate fellowship support from Genentech and has participated in advisory boards for Sanofi. F.X. Cuascut received research funding from Genentech and Biogen and has participated in advisory boards for Genentech, Biogen, Horizon, and Pharma Novartis and Horizon. G.J. Hutton received research funding from Biogen, Hoffman-La Roche, Sanofi, MedImmune, and Novartis and has participated in advisory boards for Novartis and Horizon., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system. Both the physical and mental burden of MS affect patients' health-related quality of life (HRQoL). However, there is limited research at the national level evaluating the humanistic burden among MS patients., Objectives: This study evaluated the HRQoL and functional limitations among MS patients using ten years of national survey data., Methods: Guided by the conceptual framework of the Wilson and Cleary model, this study compared HRQoL between adults diagnosed with MS (Clinical Classification Code= "080″) and non-MS adults using the 2006-2015 Medical Expenditure Panel Survey (MEPS) data. The humanistic burden included HRQoL and functional limitations. The HRQoL was evaluated using physical component summary (PCS) and mental component summary (MCS) based on the Short Form Health Survey (SF-12). The study applied the multivariable Generalized Linear Models (GLM) to estimate the marginal differences in PCS and MCS based on the SF-12. In addition, seeking help for activities of daily living (ADL) and instrumental activities of daily living (IADL) were modeled with multivariable logistic regression., Results: According to the MEPS, the estimated annual prevalence of MS was 0.52 million (95% Confidence Interval [CI]: 0.42-0.60). MS patients were mainly female (71.90%), middle aged (50-64 years, 40.21%), non-Hispanic whites (78.29%), and enrolled in private insurance plans (68.93%). The average PCS scores in MS and non-MS groups were 35.70 and 49.48, respectively. The average MCS scores were 45.58 and 51.25 for MS and non-MS groups, respectively. In addition, 18.26% of MS patients sought help for ADL, and 27.08% sought help for IADL. After adjusting for individual, biological, and environmental characteristics, the multivariable GLM with Poisson distribution indicated that the marginal difference of PCS score was 11.10 (95% CI: 9.50-12.61) units lower, and the MCS score was 4.89 (95% CI: 3.44-6.30) units lower among MS patients. In addition, MS patients were 17.32 (95% CI: 11.61-25.84) and 14.43 (95% CI: 10.09-20.65) times more likely to request assistance for ADL and IADL, respectively., Conclusions: MS was associated with lower physical and mental HRQoL than their non-MS counterparts and MS patients were more likely to request help for ADL and IADL. More work is needed to evaluate the effect of treatment strategies on improving the HRQoL and functional limitations in MS., Competing Interests: Declarations of Competing Interest None, (Copyright © 2022. Published by Elsevier B.V.)

Background: Since the introduction of oral disease-modifying agents (DMA) in 2010, the treatment options for multiple sclerosis (MS) have changed significantly. There is limited information regarding the factors associated with switching to oral DMA among prevalent injectable DMA users., Objective: This study evaluated the factors associated with switching to oral DMAs among prevalent injectable DMA users with MS., Methods: A retrospective observational cohort study using the TriNetX electronic medical records (EMR) data was conducted among patients with MS. The study included prevalent injectable DMA users with at least two injectable DMA (interferon beta-1a, interferon beta-1b, peginterferon beta-1a, or glatiramer acetate) prescription records within 6 months between September 2010 and May 2018. The second injectable DMA prescription date was considered as the index date. Switching was defined as any oral DMA prescription record (fingolimod, dimethyl fumarate, or teriflunomide) within 12 months after the index date. Patients with any infusion DMA prescription after the first injectable DMA prescription, and those less than 18 years of age were excluded from the study. The Andersen Behavioral Model was used as the conceptual framework to identify predisposing, enabling, and need factors measured during the 1-year baseline period before the index date. A multivariable logistic regression model was used to examine the predisposing (age, sex, race, and ethnicity), enabling (time-period), and need factors (comorbidities, MS symptoms, MS-related medication, and healthcare utilization) associated with switching from injectable to oral DMAs., Results: Among 2,943 prevalent injectable users included in this study, 8.09% (n=238) patients switched to oral DMAs. Patients who switched to oral DMAs were primarily younger adults aged 18-44 years (64.29%), females (82.77%), had sensory and visual symptoms, and had corticosteroid utilization during the one-year look-back period compared to non-switchers. Results from multivariable logistic regression model revealed that middle-aged adults (45-64 years, adjusted odds ratio [aOR]: 0.43, 95% Confidence Interval [CI]: 0.32-0.58), old adults (≥65 years, aOR: 0.30, 95% CI: 0.13-0.66) and men (aOR: 0.67, 95% CI: 0.47-0.96) were associated with decreased odds of switching to oral DMAs. Presence of MS-related sensory symptoms (aOR: 1.52, 95% CI: 1.07-2.16), visual symptoms (aOR: 1.59, 95% CI: 1.10-2.31), and corticosteroids usage (aOR: 1.44, 95% CI: 1.04-1.98) were associated with increased odds of switching to oral DMAs., Conclusion: The study found that about one in twelve prevalent injectable DMA users switched to oral DMA. Both demographic and clinical factors were associated with switching to oral DMAs. Further research is needed to evaluate the outcomes of switching to inform treatment decisions for MS management., (Copyright © 2022 Elsevier B.V. All rights reserved.)