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Jagadeswara R Earla,1 George J Hutton,2 J Douglas Thornton,1 Hua Chen,1 Michael L Johnson,1 Rajender R Aparasu1 1Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Houston, TX, USA; 2Department of Neurology, Baylor College of Medicine, Houston, TX, USACorrespondence: Rajender R AparasuPharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, Texas Medical Center, 4849 Calhoun Road, Houston, TX 77204-5047, USATel +1 832-842-8374Email rraparasu@uh.eduBackground: Oral fingolimod is convenient to use than injectable disease modifying agents (DMAs) in patients with multiple sclerosis (MS). However, the existing literature regarding the comparative adherence trajectories between oral fingolimod and injectable DMAs is limited.Objective: To compare the adherence trajectories between oral DMA, fingolimod, and injectable DMAs in patients with MS.Methods: A retrospective longitudinal study was conducted using adults (≥ 18 years) with MS (ICD-9-CM: 340 and a DMA prescription) from the IBM MarketScan Commercial Claims and Encounters Database between 2010 and 2012. Patients were grouped into oral fingolimod or injectable DMA users based on the index DMA among patients with MS. The annual DMA adherence trajectories, based on the proportion of days covered (PDC), were examined using group-based trajectory modeling (GBTM) during the one-year follow-up period after treatment initiation. Multivariable multinomial logistic regression using stabilized inverse probability treatment weights (IPTW) was performed to assess the association between the DMA route of administration (Oral vs Injectable) and the adherence trajectory groups. The balance of covariates between oral and injectable DMAs before and after IPTW was checked against a standardized difference threshold of 0.25.Results: The study cohort consisted of 1,700 MS patients who were initiated with oral (15.8%) or injectable (84.2%) DMAs between 2010 and 2012. The adherence rates (PDC≥ 0.8) in oral fingolimod and injectable DMA users were found to be 64.7% and 50.8%, respectively. The GBTM grouped individuals in the study cohort into three adherence trajectories – rapid discontinuers (23.5%), complete adherers (49.9%), and slow decliners (26.6%). The multinomial logistic regression model with stabilized IPTW revealed that oral fingolimod users had higher odds to be a complete adherer (adjusted odds ratio [AOR]: 2.78, 95% CI: 1.85– 4.16) or a slow discontinuer (AOR: 2.62, 95% CI: 1.70– 4.05) than injectable DMA users.Conclusions: Oral DMA fingolimod was associated with better adherence than injectable DMAs across group-based trajectories. Further research is warranted to evaluate the adherence trajectories with newer oral DMAs introduced in the last decade for MS.Keywords: group based trajectory modelling, GBTM, adherence trajectory, multiple sclerosis, disease modifying agent, DMA, fingolimod, injectable DMA

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).)

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.

Background: Fingolimod is the first approved oral disease-modifying agent (DMA) in 2010 to treat Multiple Sclerosis (MS). There is limited real-world evidence regarding the determinants associated with fingolimod use in the early years., Objective: The objective of this study was to examine the factors associated with fingolimod prescribing in the initial years after the market approval., Methods: A retrospective, longitudinal study was conducted involving adults (≥18 years) with MS from the 2010-2012 IBM MarketScan. Individuals with MS were selected based on ICD-9-CM: 340 and a newly initiated DMA prescription. Based on the index/first DMA prescription, patients were classified as fingolimod or injectable users. All covariates were measured during the six months baseline period prior to the index date. Multivariable logistic regression was performed to determine the predisposing, enabling, and need factors, conceptualized as per the Andersen Behavioral Model (ABM), associated with prescribing of fingolimod versus injectable DMA for MS., Results: The study cohort consisted of 3118 MS patients receiving DMA treatment. Of which, 14.4% of patients with MS initiated treatment with fingolimod within two years after the market entry, while the remaining 85.6% initiated with injectable DMAs. Multivariable regression revealed that the likelihood of prescribing oral DMA increased by 2-3 fold during 2011 and 2012 compared to 2010. Patients with ophthalmic (adjusted odds ratio [aOR]-2.60), heart (aOR-2.21) and urinary diseases (aOR-1.37) were more likely to receive fingolimod. Patients with other neurological disorders (aOR-0.50) were less likely to receive fingolimod than those without neurological disorders. Use of symptomatic medication (for impaired walking (aOR-2.60), bladder dysfunction (aOR-1.54), antispasmodics (aOR-1.48), and neurologist consultation (aOR-1.81) were associated with higher odds of receiving fingolimod. However, patients with non-MS associated emergency visits (aOR-0.64) had lower odds of receiving fingolimod than those without emergency visits., Conclusions: During the initial years after market approval, patients with highly active MS were more likely to receive oral fingolimod than injectable DMAs. More research is needed to understand the determinants of newer oral DMAs., Competing Interests: None., (© 2021 The Author(s).)

Multiple Sclerosis (MS) is a progressive neurodegenerative disease that affects more than 2 million people worldwide. Increasing knowledge about MS in different populations has advanced our understanding of disease epidemiology and variation in the natural history of MS among White and minority populations. In addition to differences in incidence, African American (AA) and Hispanic patients have greater disease burden and disability in earlier stages of disease compared to White patients. To further characterize MS in AA and Hispanic populations, we conducted a retrospective chart analysis of 112 patients treated at an MS center in Houston, Texas. Here, we describe similarities and differences in clinical presentation, MRI findings, treatment regimens, disability progression, and relapse rate. While we found several similarities between the groups regarding mean age, disability severity, and degree of brain atrophy at diagnosis, we also describe a few divergences. Interestingly, we found that patients who were evaluated by a neurologist at symptom onset had significantly decreased odds of greater disability [defined as Expanded Disability Status Scale (EDSS) > 4.5] at last presentation compared to patients who were not evaluated by a neurologist (OR: 0.04, 95% CI: 0.16-0.9). We also found that active smokers had significantly increased odds of greater disability both at diagnosis and at last clinical encounter compared to nonsmokers (OR: 2.44, 95% CI: 1.10-7.10, OR= 2.44, 95% CI: 1.35-6.12, p = 0.01, respectively). Additionally, we observed significant differences in treatment adherence between groups. Assessment of the degree of brain atrophy and progression over time, along with an enumeration of T1, T2, and gadolinium-enhancing brain lesions, did not reveal differences across groups.

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disorder with significant health care burden. However, little is known about health care expenditures since the introduction of oral agents for MS after 2010., Objective: To analyze health care expenditures in individuals with MS using Medical Expenditure Panel Survey (MEPS) data from 2010-2015., Methods: This retrospective cross-sectional study included adults (≥ 18 years) with MS (Clinical Classification Code 080) and those without MS based on the 2010-2015 full year consolidated MEPS Household Component and Medical Provider Component data files. Descriptive weighted analyses were performed to compare health care expenditures between individuals with MS and without MS. The 2-part model involving probit and generalized linear models was used to estimate the marginal increase in total health care expenditures for MS patients., Results: There were 0.61 million patients (95% CI = 0.50-0.72) diagnosed with MS annually, accounting for a prevalence of 0.25%. The 2-part model revealed that the marginal total health care expenditures in patients diagnosed with MS were $20,103.49 (95% CI = $14,516.24-$25,690.73) more compared with those without MS. Further, the mean adjusted prescription medication expenditures for the MS group were $13,092.16 (95% CI = $9,452.20-$16,732.12) higher than the non-MS group and accounted for 65.12% of total health care expenditures in MS., Conclusions: MS is an expensive neuroinflammatory disease with a majority of the burden attributable to prescription medications. High prescription expenditure burden can be a barrier to optimal patient care in MS., Disclosures: No funding was received for this study. Hutton reports grants from Adamas, Biogen, EMD Serono, Genzyme, Hoffman-LaRoche, MedImmune, Mallinckrodt, and Novartis and fees from Biogen, Celgene, Genzyme, Genentech, and Novartis, outside the submitted work. Aparasu reports grants from Novartis, Incyte, and Astellas, outside the submitted work. Earla and Thornton have nothing to disclose. Part of the study findings was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2019 National Conference; May 18-22, 2019; New Orleans, LA.

Multiple sclerosis (MS) is an autoimmune inflammatory disease affecting the central nervous system leading to demyelination. MS in the pediatric population is rare, but has been shown to lead to significant disability over the duration of the disease. As we have learned more about pediatric MS, there has been a development of improved diagnostic criteria leading to earlier diagnosis, earlier initiation of disease-modifying therapies (DMT), and an increasing number of DMT used in the treatment of pediatric MS. Over time, treatment with DMT has trended towards the initiation of higher efficacy treatment at time of diagnosis to help prevent further disease progression and accrual of disability over time, and there is evidence in current literature that supports this change in treatment patterns. In this review, we discuss the current knowledge in diagnosis, treatment, and clinical outcomes in pediatric MS.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune disease of the central nervous system (CNS). Disease-modifying therapies (DMT) targeting inflammation have been shown to reduce disease activity in patients with relapsing⁻remitting MS (RRMS). The current therapeutic challenge is to find an effective treatment to halt disease progression and reverse established neural damage. Stem cell-based therapies have emerged to address this dilemma. Several types of stem cells have been considered for clinical use, such as autologous hematopoietic (aHSC), mesenchymal (MSC), neuronal (NSC), human embryonic (hESC), and induced pluripotent (iPSC) stem cells. There is convincing evidence that immunoablation followed by hematopoietic therapy (aHSCT) has a high efficacy for suppressing inflammatory MS activity and improving neurological disability in patients with RRMS. In addition, MSC therapy may be a safe and tolerable treatment, but its clinical value is still under evaluation. Various studies have shown early promising results with other cellular therapies for CNS repair and decreasing inflammation. In this review, we discuss the current knowledge and limitations of different stem cell-based therapies for the treatment of patients with MS.

Background: Dalfampridine extended-release (ER) tablets, 10 mg twice daily, have been shown to improve walking in people with multiple sclerosis. We evaluated the safety and efficacy of dalfampridine-ER 5 mg compared with 10 mg., Methods: Patients were randomized to double-blind treatment with twice-daily dalfampridine-ER tablets, 5 mg (n = 144) or 10 mg (n = 143), or placebo (n = 143) for 4 weeks. Primary efficacy endpoint was change from baseline walking speed by the Timed 25-Foot Walk 3 to 4 hours after the last dose. At 40% of sites, 2-week change from baseline walking distance was measured by the 6-Minute Walk test., Results: At 4 weeks, walking speed changes from baseline were 0.363, 0.423, and 0.478 ft/s (placebo, dalfampridine-ER 5 mg, and dalfampridine-ER 10 mg, respectively [P = NS]). Post hoc analysis of average changes between pretreatment and on-treatment showed that relative to placebo, only dalfampridine-ER 10 mg demonstrated a significant increase in walking speed (mean ± SE): 0.443 ± 0.042 ft/s versus 0.303 ± 0.038 ft/s (P = .014). Improvement in 6-Minute Walk distance was significantly greater with dalfampridine-ER 10 mg (128.6 ft, P = .014) but not with 5 mg (76.8 ft, P = .308) relative to placebo (41.7 ft). Adverse events were consistent with previous studies. No seizures were reported., Conclusions: Dalfampridine-ER 5 and 10 mg twice daily did not demonstrate efficacy on the planned endpoint. Post hoc analyses demonstrated significant increases in walking speed relative to placebo with dalfampridine-ER 10 mg. No new safety signals were observed.

Multiple sclerosis (MS) is most prevalent in women of childbearing age. It is well established that the relapse rate decreases during pregnancy but increases significantly during the first postpartum trimester. The objective of this retrospective study was to evaluate the effectiveness of the administration of 1 g of intravenous methylprednisolone (IVMP) after delivery in the prevention of MS relapses. The study involved 47 women with one or more documented pregnancies; each pregnancy was treated as a separate case. There were 50 cases with relapsing-remitting MS and 2 with secondary progressive MS. The cases were divided into two groups: the IVMP group (those who received 1 g of IVMP after delivery) and the no-IVMP group (those who did not receive IVMP after delivery). There were 39 cases in the IVMP group and 13 in the no-IVMP group. During the first postpartum trimester, relapses occurred in 17.9% of the IVMP group, compared with 46.2% of the no-IVMP group (P = .0448). The difference in relapse percentage between the two groups during the second and third postpartum trimesters was not statistically significant. Our study shows a statistically significant benefit of postpartum IVMP administration in reducing MS relapses.

In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.