Treatment Options For Multiple Sclerosis Research Articles

Drug Repurposing and Screening for Multiple Sclerosis Targeting Microglia and Macrophages.

Microglia/macrophages (MG/Mφ) play a central role in the pathogenesis of multiple sclerosis (MS). However, the intricacies of the immunomodulatory microenvironment in MS, particularly the heterogeneity and regulatory mechanisms of MG/Mφ subpopulations, remain elusive. The commonly used treatment options for MS have several drawbacks, such as significant side effects and uncertain efficacy. The exploration of developing new drugs targeting MG/Mφ for the treatment of MS remains to be investigated. We identified three distinct subpopulations of MG/Mφ, among which MG/Mφ_3 significantly increased as the experimental autoimmune encephalomyelitis (EAE) progressed. Ifenprodil and RO-25-6981 demonstrated notable inhibition of inflammatory factor expression, accompanied by reduced cytotoxicity. The interaction modes of these compounds with the common binding pocket in the GluN1b-GluN2B amino terminal domain heterodimer were elucidated. Virtual docking, based on the N-methyl-D-aspartate (NMDA) receptor, showed that homo-skeleton compounds of ifenprodil potentially exhibit low binding free energy with the receptor, including eliprodil and volinanserin. In vitro cell models corroborated the effective inhibition of inflammatory factor expression and minimal cytotoxicity of eliprodil and volinanserin. CoMFA (standard error of estimate = 0.378, R2 = 0.928, F values = 241.255, Prob. of R2 = 0) and topomer CoMFA (q2 = 0.553, q2 stderr = 0.77, intercept = - 1.48, r2 = 0.908, r2 stderr = 0.35) were established based on the inhibitors of NMDA receptor. The contour maps of CoMFA and topomer CoMFA models give structural information to improve the inhibitory function. This study underscores the involvement of MG/Mφ in inflammatory pathways during MS progression and offers promising compound candidates for MS therapy targeting MG/Mφ.

Reasons for Hospital Admission in Individuals With Multiple Sclerosis.

Health care utilization is higher in individuals with multiple sclerosis (MS) than in the general population. However, there are limited data on the reasons for their hospital admissions. Our primary objective is to analyze the reasons for the hospitalization of individuals with MS with the goal of identifying preventable causes. We conducted a retrospective analysis of a cohort of adults with a confirmed diagnosis of MS admitted to Duke University Hospital between January 2018 and January 2020. This yielded a cohort of 210 individuals. Data were analyzed using descriptive statistics. The most common reason for admission was urinary tract infection (UTI; 10.3%). The average length of stay was 6.1 days for the individuals with MS vs 5.5 days for the general population. The 30-day readmission rates were 14.9% and 15.5%, respectively. A significant number of admitted patients were not on any disease-modifying therapy (DMT), and no difference in median age was identified between those with a DMT vs those without. Length of stay and readmission rates were similar to those of the general population in this contemporary cohort. Given the prevalence of bladder dysfunction in MS, it is not surprising that a UTI was the most common reason for admission. Actively addressing management of and techniques for bladder dysfunction may decrease the admission rate for individuals with MS. Though we now have more treatment options for MS, many individuals with the highest health care utilization are not on a DMT. Future research is needed to identify the factors that can be addressed to support these patients and reduce preventable hospitalizations.

Treating to target in multiple sclerosis: Do we know how to measure whether we hit it?

The rapidly evolving landscape of effective treatment options in multiple sclerosis has led to a shift of treatment objectives towards a treat-to-target approach aiming to suppress disease activity below the level of detectability early during the disease. To enable treat-to-target, a thorough reappraisal of available outcome measures with respect to their ability in this regard is required. To that end, we conducted a comprehensive systematic literature review of more than 1000 studies using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 methodology focusing on underlying evidence as well as utility and implementability in clinical practice. From there, we propose a set of measurable outcomes for everyday routine clinical practice as well as advanced/aspirational measurables requiring additional resources. We also outline remaining knowledge/technology gaps that need to be overcome to enable a treat-to-target approach. This work provides the basis for an evidence-based definition of outcome targets for relevant stakeholders and regulatory authorities.

B-cell Therapy for Multiple Sclerosis

B-cell therapy using anti-CD20 antibodies significantly suppresses relapse and is therefore an important treatment option for multiple sclerosis (MS). Based on the production of inflammatory cytokines and enhanced antigen-presenting capacity, B cells trigger MS relapses via activation of pathogenic T cells. Suppression of these abnormal actions of B cells is the primary mechanism underlying relapse prevention using B-cell therapies. Treatments that target B cells are also expected to suppress chronic progression of MS through modulation of B-cell activity within the central nervous system. B-cell therapies based on novel approaches are expected to improve the regulation of acute and chronic MS pathology.

Clinicoradiological Factors for Predicting and Monitoring the Progression of Multiple Sclerosis

As knowledge of pathophysiology and treatment options for multiple sclerosis has been expanding, decisions about when and which drugs we should start and switch appropriately have became important. It should be based upon individuals’ baseline clinical, environmental, demographical, and radiological biomarkers that correlate with long-term disability. In addition, a timely assessment of treatment response and adverse effect should be followed after the initial treatment. Several prognostication tools were developed and large longitudinal studies validated them. They consisted of composition of demographical factors, clinical relapse rate, relapse severity, involvement of specific functional system, magnetic resonance imaging activity and characteristic findings (gadolinium enhancement, brain atrophy, and paramagnetic rim lesion, etc.).

Clinicoradiological Factors for Predicting and Monitoring the Progression of Multiple Sclerosis

As knowledge of pathophysiology and treatment options for multiple sclerosis has been expanding, decisions about when and which drugs we should start and switch appropriately have became important. It should be based upon individuals’ baseline clinical, environmental, demographical, and radiological biomarkers that correlate with long-term disability. In addition, a timely assessment of treatment response and adverse effect should be followed after the initial treatment. Several prognostication tools were developed and large longitudinal studies validated them. They consisted of composition of demographical factors, clinical relapse rate, relapse severity, involvement of specific functional system, magnetic resonance imaging activity and characteristic findings (gadolinium enhancement, brain atrophy, and paramagnetic rim lesion, etc.).

Montelukast as a repurposable additive drug for standard-efficacy multiple sclerosis treatment: Emulating clinical trials with retrospective administrative health claims data

Background: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach. Objective: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS). Methods: In this retrospective case–control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18–65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum’s Clinformatics® Data Mart (CDM) and IQVIA PharMetrics® Plus for Academics. Cases included 483 pwMS on montelukast and with medication adherence in CDM and 208 in PharMetrics Plus for Academics. We randomly sampled controls from 35,330 pwMS without montelukast prescriptions in CDM and 10,128 in PharMetrics Plus for Academics. Relapses were measured over a 2-year period through inpatient hospitalization and corticosteroid claims. A doubly robust causal inference model estimated the effects of montelukast, adjusting for confounders and censored patients. Results: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared to non-users in 67.3% of emulated RCTs. Conclusion: Real-world evidence suggested that montelukast reduces MS relapses, warranting future clinical trials and further research on LTRAs’ potential mechanism in MS.

Safety and clinical effectiveness of peginterferon beta-1a for relapsing multiple sclerosis in a real-world setting: Final results from the Plegridy Observational Program.

Interferon beta-1a remains an important treatment option for multiple sclerosis, particularly when safety or tolerability concerns may outweigh the benefits of higher-efficacy disease-modifying therapies. The five-year phase 4 Plegridy Observational Program (POP) study (NCT02230969) collected data on real-world safety and effectiveness of Plegridy® (peginterferon beta-1a) treatment in patients with relapsing multiple sclerosis. To explore the real-world safety and effectiveness of peginterferon beta-1a in patients with relapsing multiple sclerosis, including factors influencing treatment discontinuation. Data were collected prospectively from patients ≥ 18 years old with relapsing multiple sclerosis for overall population analysis and for subpopulations including newly/previously diagnosed patients, age, and experience with peginterferon beta-1a. Outcome measures included annualized relapse rates, adverse events, and predictors of time to treatment discontinuation. Mean (SD) treatment duration in the overall population (N = 1172) was 896.0 (733.15) days. Incidence of adverse events was higher in new than experienced users (79.4% vs. 57.0%). New users were more likely than experienced users to discontinue (hazard ratio = 1.60; P < 0.0001). The adjusted annualized relapse rate was 0.09, and at the end of 5 years, 77.1% of patients were relapse-free. Peginterferon beta-1a is an effective therapy for managing relapsing multiple sclerosis. The identification of predictors of discontinuation can help inform strategies to enhance treatment persistence.

A comparison of clinical, utilization, and cost outcomes between oral treatments for multiple sclerosis.

Multiple sclerosis (MS) affects nearly 1 million people in the United States and causes significant disability and economic loss. Among the first available oral MS treatment options, clinical outcome comparisons and associated health care resource utilization are not clearly defined. To compare MS outcomes, health care resource utilization, and relative costs across treatment with dimethyl fumarate (DMF), fingolimod (FG), or teriflunomide (TERI) among Medicare Advantage Prescription Drug (MAPD) plan and commercially insured beneficiaries. This retrospective cohort study used the Humana Research Database. Eligible study patients had their first MS medication claim for oral DMG, FG, or TERI between January 1, 2013, and December 31, 2018. Patients were followed for a minimum of 12 months (mean follow-up = 3.8 years), until the earliest of the following occurred: health plan disenrollment, the end of the study period, or death. Study cohorts were balanced with inverse probability of treatment weighting. All-cause and MS-related health care resource utilization, time on therapy, and time after therapy were compared using inverse probability of treatment-adjusted multivariate generalized linear models across treatment groups. Relative costs were compared using a generalized linear model with a gamma distribution and log link. We identified 1,442 patients in 3 medication groups: DMF (n = 843), FG (n = 213), and TERI (n = 386). After weighting, there were no significant differences between the medication groups on demographic and clinical characteristics. Time on therapy (days) was significantly different across medication groups (P < 0.001). Time on therapy was longest for FG compared with the DM and TERI groups (644 vs 462 vs 521). The number discontinuing the index medication was significantly different for FG vs DMF vs TERI (74.7% vs 85.3% vs 80.7%; P < 0.001). FG had the lowest discontinuation rate. The mean (SD) annualized relapse rates (ARRs) were 0.47 (0.80), 0.42 (1.3), and 0.53 (1.3) (P = 0.037) for DMF, FG, and TERI, respectively. The percentage of those experiencing inpatient stays and the number of stays (mean [SD]) were significantly different among the FG group vs DMF vs TERI (29.9% vs 34.1% vs 40.9%; P < 0.001) and (0.57 [2.9] vs 0.74 [1.9] vs 0.91 [3.5]; P = 0.007), respectively. All-cause emergency department visits and the number of visits (mean [SD]) were significantly different for the FG cohort vs DMF vs TERI (46% vs 54.3% vs 61%; P < 0.001) and (1.84 [7.7] vs 2.38 [5.9] vs 2.87 [8.8]; P = 0.002), respectively. FG had the lowest impatient stays and emergency department visits of the 3 groups. Patients with MS initiated on FG used fewer health care resources and experienced lower ARR compared with patients on DMF and TERI.

Repeated iv anti-CD20 treatment in multiple sclerosis: Long-term effects on peripheral immune cell subsets.

Repeated intravenous administration of anti-CD20 depleting monoclonal antibodies 6 months apart is among the highly effective treatment options in multiple sclerosis (MS). Here, we aimed to investigate peripheral immune cell subset depletion kinetics following either rituximab (RTX) or ocrelizumab (OCR) infusions in people with MS (pwMS). We studied pwMS treated de-novo with either RTX (n = 7) or OCR (n = 8). The examinations were scheduled before the initiation of anti-CD20 therapy and every 12 weeks for up to 15 months. Immunophenotyping of immune cell subsets in peripheral blood was performed by multiparametric fluorescence cytometry. A significant, persistent decrease of CD19+ B cells was observed already with the first anti-CD20 infusion (p < 0.0001). A significant proportional reduction of memory B cells within the B-cell pool was achieved only after two treatment cycles (p = 0.005). We observed a proportional increase of immature (p = 0.04) and naive B cells (p = 0.004), again only after the second treatment cycle. As for the peripheral T-cell pool, we observed a continuous proportional increase of memory T helper (TH) cells/central memory TH cells (p = 0.02/p = 0.008), while the number of regulatory T cells (Treg) decreased (p = 0.007). The percentage of B-cell dependent TH17.1 central memory cells dropped after the second treatment cycle (p = 0.02). No significant differences in the depletion kinetics between RTX and OCR were found. Peripheral immune cell profiling revealed more differentiated insights into the prompt and delayed immunological effects of repeated intravenous anti-CD20 treatment. The observation of proportional changes of some pathogenetically relevant immune cell subsets only after two infusion cycles deserves further attention.

Potential of Nano-Engineered Stem Cells in the Treatment of Multiple Sclerosis: A Comprehensive Review.

Multiple sclerosis (MS) is a chronic and degrading autoimmune disorder mainly targeting the central nervous system, leading to progressive neurodegeneration, demyelination, and axonal damage. Current treatment options for MS are limited in efficacy, generally linked to adverse side effects, and do not offer a cure. Stem cell therapies have emerged as a promising therapeutic strategy for MS, potentially promoting remyelination, exerting immunomodulatory effects and protecting against neurodegeneration. Therefore, this review article focussed on the potential of nano-engineering in stem cells as a therapeutic approach for MS, focusing on the synergistic effects of combining stem cell biology with nanotechnology to stimulate the proliferation of oligodendrocytes (OLs) from neural stem cells and OL precursor cells, by manipulating neural signalling pathways-PDGF, BMP, Wnt, Notch and their essential genes such as Sox, bHLH, Nkx. Here we discuss the pathophysiology of MS, the use of various types of stem cells in MS treatment and their mechanisms of action. In the context of nanotechnology, we present an overview of its applications in the medical and research field and discuss different methods and materials used to nano-engineer stem cells, including surface modification, biomaterials and scaffolds, and nanoparticle-based delivery systems. We further elaborate on nano-engineered stem cell techniques, such as nano script, nano-exosome hybrid, nano-topography and their potentials in MS. The article also highlights enhanced homing, engraftment, and survival of nano-engineered stem cells, targeted and controlled release of therapeutic agents, and immunomodulatory and tissue repair effects with their challenges and limitations. This visual illustration depicts the process of utilizing nano-engineering in stem cells and exosomes for the purpose of delivering more accurate and improved treatments for Multiple Sclerosis (MS). This approach targets specifically the creation of oligodendrocytes, the breakdown of which is the primary pathological factor in MS.

The Potential Role of Fecal Microbiota Transplant in the Reversal or Stabilization of Multiple Sclerosis Symptoms: A Literature Review on Efficacy and Safety.

Multiple sclerosis (MS) affects millions of people worldwide, and recent data have identified the potential role of the gut microbiome in inducing autoimmunity in MS patients. To investigate the potential of fecal microbiota transplant (FMT) as a treatment option for MS, we conducted a comprehensive literature search (PubMed/Medline, Embase, Web of Science, Scopus, and Cochrane) and identified five studies that involved 15 adult MS patients who received FMT for gastrointestinal symptoms. The primary outcome of this review was to assess the effect of FMT in reversing and improving motor symptoms in MS patients, while the secondary outcome was to evaluate the safety of FMT in this patient population. Our findings suggest that all 15 patients who received FMT experienced improved and reversed neurological symptoms secondary to MS. This improvement was sustained even in follow-up years, with no adverse effects observed. These results indicate that FMT may hold promise as a treatment option for MS, although further research is necessary to confirm these findings.

The State of the Art of Pediatric Multiple Sclerosis.

Multiple sclerosis (MS) represents a chronic immune-mediated neurodegenerative disease of the central nervous system that generally debuts around the age of 20-30 years. Still, in recent years, MS has been increasingly recognized among the pediatric population, being characterized by several peculiar features compared to adult-onset disease. Unfortunately, the etiology and disease mechanisms are poorly understood, rendering the already limited MS treatment options with uncertain efficacy and safety in pediatric patients. Thus, this review aims to shed some light on the progress in MS therapeutic strategies specifically addressed to children and adolescents. In this regard, the present paper briefly discusses the etiology, risk factors, comorbidities, and diagnosis possibilities for pediatric-onset MS (POMS), further moving to a detailed presentation of current treatment strategies, recent clinical trials, and emerging alternatives. Particularly, promising care solutions are indicated, including new treatment formulations, stem cell therapies, and cognitive training methods.

Autologous hematopoietic stem cell transplantation in multiple sclerosis: A 20-year single center’s experience in Mexico. (P14-3.015)

<h3>Objective:</h3> To describe the clinical characteristics and clinical outcomes of AHSCT in Mexican patients. <h3>Background:</h3> Autologous Hematopoietic Stem Cell treatment (AHSCT) is an immune reconstitution treatment option for Multiple Sclerosis (MS) that has grown in clinical evidence over the last decades; detailed efficacy and safety data is still lacking, especially outcomes data from low-income countries. <h3>Design/Methods:</h3> Retrospective single-center observational study of all MS patients that underwent AHSCT in a single reference center in Mexico City from January 2000 to January 2020. <h3>Results:</h3> We identified 24 patients, of which 22 had at least one year of follow-up after AHSCT and underwent analysis for clinical outcome. The median follow-up time was 85 months (range: 12–267); with a median age of 44.0 years (IR 38–52); 62.8% (n=15) were men and 31.8% (n=7) women; 50% were secondary progressive forms of MS (SPMS), and 27.3% were relapsing-remitting MS (RRMS); 59% (n=13) met the criteria for highly active MS (HAMS). The composite score of no evidence of disease activity 3 or NEDA3 (no relapses, no new MRI lesions, and no EDSS progression) was achieved in all the patients at a 24-month follow-up and in 72.1% (n=16) of the patients at the time of the last follow up visit. Relapse-free survival at the last follow-up visit was achieved at 77.3%; MRI event-free survival at 90.9%; Expanded disability status scale score progression-free survival in 95.4%. Only one patient required the re-initiation of disease-modifying therapy. There was no treatment-related mortality. One patient was diagnosed with premature ovarian failure. <h3>Conclusions:</h3> AHSCT in Mexican MS patients is an effective and relatively safe treatment option with no mortality and can be performed with a reasonable degree of safety at experienced centers. <b>Disclosure:</b> Dr. Rodriguez Estrada has nothing to disclose. Dr. Molina Carrion has nothing to disclose.

Treatment Courses of Patients Newly Diagnosed with Multiple Sclerosis in 2012-2018.

Treatment options for multiple sclerosis (MS) are now numerous, but it is unclear which Disease-Modifying Treatment (DMT) is the optimal choice for a given patient. Treatment switches are common, both because of side effects and because of lack of efficacy. There are few data available on the treatment courses of patients newly diagnosed with MS in the current DMT era. All patients newly diagnosed with MS in 2012-2018 at North Karelia Central Hospital were identified (N = 55), and those with complete follow-up data available (N = 43) were included. The minimum follow-up from diagnosis was 44 months with a maximum of 9 years. Seven patients (16%) had no DMT at any time during the follow-up. Treatment was most often initiated with interferon or glatiramer acetate (69%), but 72% of these treatments were discontinued. After cladribine, teriflunomide and fingolimod showed the best treatment persistence. Patients who experienced their first MS symptoms at ≥40 years of age all continued with their initial treatment category until the end of the follow-up. In a third of the patients who had received a DMT, at the end of the follow-up, the treatment had been escalated to fingolimod, cladribine or natalizumab. Only 13 patients (28%) continued with their initial DMT until the end of the follow-up.

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm.

Multiple Sclerosis (MS) is a neuroinflammatory disorder, which is histopathologically characterized by multifocal inflammatory demyelinating lesions affecting both the central nervous system’s white and grey matter. Especially during the progressive phases of the disease, immunomodulatory treatment strategies lose their effectiveness. To develop novel progressive MS treatment options, pre-clinical animal models are indispensable. Among the various different models, the cuprizone de- and remyelination model is frequently used. While most studies determine tissue damage and repair at the histological and ultrastructural level, functional readouts are less commonly applied. Among the various overt functional deficits, gait and coordination abnormalities are commonly observed in MS patients. Motor behavior is mediated by a complex neural network that originates in the cortex and terminates in the skeletal muscles. Several methods exist to determine gait abnormalities in small rodents, including the rotarod testing paradigm. In this review article, we provide an overview of the validity and characteristics of the rotarod test in cuprizone-intoxicated mice.

Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician's Review.

Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by inflammation and demyelination for which there is currently no cure; therefore, the aim of therapy is to reduce the risk of relapse and disability progression. The treatment options for MS have increased greatly in recent years with the development of several disease-modifying therapies (DMTs) and the advent of immune reconstitution therapy (IRT). IRTs are administered in short-dosing periods to produce long-term effects on the immune system. Treatment with an IRT is based on the 3Rs: reduction, repopulation, and reconstitution of lymphocytes, which leads to restoration of immune effector functions. Cladribine tablets represent a selective, high-efficacy, oral form of IRT for patients with MS that targets lymphocytes and spares innate immune cells. Patients require only two weekly treatment courses, with each course comprising two treatment weeks, in Years 1 and 2; therefore, cladribine tablets are associated with a lower monitoring burden than many other DMTs, while short dosing periods can help to improve adherence. This review provides an overview of IRT and offers the clinician’s perspective on the current MS treatment landscape, with a focus on practical advice for the management of patients undergoing treatment with cladribine tablets based on the most recent evidence available, including risks associated with COVID-19 and recommendations for vaccination in patients with MS.

FACTORS ASSOCIATED WITH SWITCHING FROM INJECTABLE TO ORAL DISEASE MODIFYING AGENTS AMONG PATIENTS WITH MULTIPLE SCLEROSIS

BackgroundSince 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. ObjectiveThis study evaluated the factors associated with switching to oral DMAs among prevalent injectable DMA users with MS. MethodsA 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. ResultsAmong 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. ConclusionThe 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.

Peginterferon beta-1a concentrations in breast milk of lactating multiple sclerosis patients

BackgroundPeginterferon beta-1a is an interferon beta-1a formulation that has been pegylated, resulting in a longer half-life than other interferon beta formulations. We examined concentrations of peginterferon beta-1a in breast milk of lactating patients with multiple sclerosis (MS) receiving peginterferon beta-1a as their postpartum disease-modifying therapy. MethodsAfter completion of titration to a full dose of peginterferon beta-1a and following a single full dose peginterferon beta-1a injection (125 µg), breast milk samples (≥10 mL) were collected by 5 women on days 1–14 post injection. Peginterferon beta-1a concentrations in breast milk samples were measured by a qualified enzyme-linked immunosorbent assay (detection threshold: 15 pg/mL). Mean and median daily concentrations and median maximum concentration (Cmax), time of Cmax (Tmax), time of last measurable concentration (Tlast), area under the concentration-time curve (AUClast), and relative infant dose (RID) were determined. ResultsAfter receiving a single full dose peginterferon beta-1a injection, the maximum breast milk concentration recorded in an individual patient was 126.2 pg/mL (0.00013 µg/mL) on day 6. The remaining patients all had maximum breast milk concentrations <72 pg/mL. The geometric mean of Cmax was 48.9 pg/mL and the median Tmax and Tlast were 4 and 7 days, respectively. The median AUClast was 210.9 day*pg/mL. Among the 5 study patients, the mean breast milk concentration across all study days was 35.95 pg/mL, with an estimated RID of 0.0054% of the maternal dose. ConclusionMinimal concentrations of peginterferon beta-1a were detected in the breast milk samples. These findings may be useful for clinicians considering postpartum MS treatment options.

Treatment Options in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

There are few diseases where as much therapeutic progress has been made in recent years as in multiple sclerosis. Nine different drug classes with more than a dozen approved therapies are now available. Similarly, there have been unimaginable advances in understanding neuromyelitis optica (now neuromyelitis optica spectrum disorder [NMOSD]) over the past 15 years. Building on the knowledge gained, the first therapies have been approved in recent years. In this review, we aim to present all therapies approved for the treatment of MS or NMOSD. The different forms of application, different approval criteria and most important side effects will be presented. This work is intended for physicians who are interested in MS and NMOSD therapies and want to get a first overview and does not replace the respective guidelines of the regulatory authorities.