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Journal of Managed Care & Specialty... Feb 2024Multiple sclerosis (MS) affects nearly 1 million people in the United States and causes significant disability and economic loss. Among the first available oral MS...
BACKGROUND
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.
OBJECTIVE
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.
METHODS
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.
RESULTS
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 ( < 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%; < 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) ( = 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%; < 0.001) and (0.57 [2.9] vs 0.74 [1.9] vs 0.91 [3.5]; = 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%; < 0.001) and (1.84 [7.7] vs 2.38 [5.9] vs 2.87 [8.8]; = 0.002), respectively. FG had the lowest impatient stays and emergency department visits of the 3 groups.
CONCLUSIONS
Patients with MS initiated on FG used fewer health care resources and experienced lower ARR compared with patients on DMF and TERI.
Topics: Aged; Humans; United States; Multiple Sclerosis; Retrospective Studies; Medicare; Fingolimod Hydrochloride; Dimethyl Fumarate
PubMed: 38308623
DOI: 10.18553/jmcp.2024.30.2.129 -
Nature Communications Jan 2024Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised,... (Randomized Controlled Trial)
Randomized Controlled Trial
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.
Topics: Adult; Humans; COVID-19; Dimethyl Fumarate; SARS-CoV-2; Hospitalization; Hospitals; Treatment Outcome
PubMed: 38296965
DOI: 10.1038/s41467-023-43644-x -
Cureus Dec 2023Herpes zoster (HZ) infection results from the reactivation of the varicella-zoster virus (VZV), which remains dormant in the dorsal root ganglia after an initial...
Herpes zoster (HZ) infection results from the reactivation of the varicella-zoster virus (VZV), which remains dormant in the dorsal root ganglia after an initial chickenpox infection. Although HZ appears more common in people with multiple sclerosis (MS) than expected in the general population, few studies have investigated this association, particularly with a normal absolute lymphocyte count (ALC). Additionally, no reported cases have discussed the clinical presentation of such patients. This report describes the case of a 26-year-old female with a known history of relapsing-remitting MS on dimethyl fumarate (DMF) treatment. She presented with a history of painful erythematous blisters, diagnosed as acute HZ infection with a normal ALC. This case provides evidence that warrants further research and attention to the management of patients with MS receiving DMF, particularly regarding infectious risks. It highlights the importance of pharmacovigilance and the potential benefits of VZV and HZ immunization in DMF recipients.
PubMed: 38292998
DOI: 10.7759/cureus.51412 -
Multiple Sclerosis (Houndmills,... Feb 2024Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women.
BACKGROUND
Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women.
OBJECTIVE
To assess the use of MS disease-modifying therapies (DMTs) during pregnancy in France over the last decade, marked by an increasing DMTs availability.
METHODS
All pregnancies ended from April 2010 to December 2021 in women with MS were identified based on the nationwide Mother-Child Register EPI-MERES, built from the French National Health Data System ( (SNDS)).
RESULTS
Of a total of 20,567 pregnancies in women with MS, 7587 were exposed to DMT. The number of DMT-exposed pregnancies markedly increased from 1079 in 2010-2012 to 2413 in 2019-2021 (+124%), especially those exposed to glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20. Among pregnancies of women on DMT 6 months before pregnancy, 78.0% underwent DMT discontinuation and 7.6% switched DMT, generally before (33.0% and 77.0%, respectively) or during the first trimester of pregnancy (58.3% and 17.8%, respectively). DMT discontinuation decreased from 84.0% in 2010-2012 to 72.4% in 2019-2021 and was less frequent among women aged ⩾35 years and those socioeconomically disadvantaged.
CONCLUSION
Despite MS therapeutic management adaptations to pregnancy, exposure during pregnancy to treatments whose safety profile has not yet been clearly established has increased sharply over the last decade.
Topics: Humans; Female; Pregnancy; Multiple Sclerosis; Natalizumab; Glatiramer Acetate; Dimethyl Fumarate; France; Multiple Sclerosis, Relapsing-Remitting; Immunosuppressive Agents
PubMed: 38281078
DOI: 10.1177/13524585231223395 -
Journal of the Neurological Sciences Feb 2024Predictive and prognostic biomarkers for multiple sclerosis (MS) remain a significant gap in MS diagnosis and treatment monitoring. Currently, there are no timely...
High temperature requirement A1 and macrophage migration inhibitory factor in the cerebrospinal fluid; a potential marker of conversion from relapsing-remitting to secondary progressive multiple sclerosis.
BACKGROUND
Predictive and prognostic biomarkers for multiple sclerosis (MS) remain a significant gap in MS diagnosis and treatment monitoring. Currently, there are no timely markers to diagnose the transition to secondary progressive MS (SPMS).
OBJECTIVE
This study aims to evaluate the discriminatory potential of the High temperature requirement serine protease (HTRA1)/Macrophage migration inhibitory factor (MIF) cerebrospinal fluid (CSF) ratio in distinguishing relapsing-remitting (RRMS) patients from SPMS patients.
METHODS
The MIF and HTRA1 CSF levels were determined using ELISA in healthy controls (n = 23), RRMS patients before (n = 22) and after 1 year of dimethyl fumarate treatment (n = 11), as well as in SPMS patients before (n = 11) and after 2 years of mitoxantrone treatment (n = 7). The ability of the HTRA1/MIF ratio to discriminate the different groups was determined using receiver operating curve (ROC) analyses.
RESULTS
The ratio was significantly increased in treatment naïve RRMS patients while decreased again in SPMS patients at baseline. Systemic administrated disease modifying treatment (DMT) only significantly affected the ratio in RRMS patients. ROC analysis demonstrated that the ratio could discriminate treatment naïve RRMS patients from SPMS patients with 91% sensitivity and 100% specificity.
CONCLUSION
The HTRA1/MIF ratio is a strong candidate as a MS biomarker for SPMS conversion.
Topics: Humans; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Macrophage Migration-Inhibitory Factors; Temperature
PubMed: 38278096
DOI: 10.1016/j.jns.2024.122888 -
Journal of Comparative Effectiveness... Feb 2024Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bias. We show that corresponding...
Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bias. We show that corresponding treatment effect estimates may have limited external validity, and propose two visualization tools to clarify the target estimand. We conduct a simulation study to demonstrate, with bivariate ellipses and joy plots, that differences in covariate distributions across treatment groups may affect the external validity of treatment effect estimates. We showcase how these visualization tools can facilitate the interpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF) and natalizumab (NAT) on manual dexterity in patients with multiple sclerosis. In the simulation study, estimates of the treatment effect greatly differed depending on the target population. For example, when comparing treatment B with C, the estimated treatment effect (and respective standard error) varied from -0.27 (0.03) to -0.37 (0.04) in the type of patients initially receiving treatment B and C, respectively. Visualization of the matched samples revealed that covariate distributions vary for each comparison and cannot be used to target one common treatment effect for the three treatment comparisons. In the case study, the bivariate distribution of age and disease duration varied across the population of patients receiving TERI, DMF or NAT. Although results suggest that DMF and NAT improve manual dexterity at 1 year compared with TERI, the effectiveness of DMF versus NAT differs depending on which target estimand is used. Visualization tools may help to clarify the target population in comparative effectiveness studies and resolve ambiguity about the interpretation of estimated treatment effects.
Topics: Humans; Immunosuppressive Agents; Fingolimod Hydrochloride; Multiple Sclerosis, Relapsing-Remitting; Dimethyl Fumarate; Multiple Sclerosis; Crotonates; Hydroxybutyrates; Nitriles; Toluidines
PubMed: 38261336
DOI: 10.57264/cer-2023-0089 -
Neurologia I Neurochirurgia Polska 2024The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe...
CLINICAL RATIONALE FOR THE STUDY
The rapid spread of SARS-CoV-2 throughout the world has highlighted the importance of vaccinations to control the pandemic and to protect people at risk for severe disease courses. Disease-modifying therapies (DMT) in multiple sclerosis (MS), whether immunomodulatory or immunosuppressive, may affect the immune response. Therefore, the question arose as to whether these vaccinations would be effective.
AIM OF THE STUDY
We planned a study to assess the immune response to SARS-CoV-2 vaccines by type of therapy.
MATERIAL AND METHODS
Participants were recruited from 14 Polish MS centres. The data was obtained by neurologists using a questionnaire. We collected data on 353 MS patients (269 females, 84 males) who received complete primary SARS-CoV-2 vaccination. All persons with MS (PwMS) were treated with disease-modifying therapies.
RESULTS
305 out of 353 PwMS (86.4%) were positive for IgG Abs against SARS-CoV-2 S domain S1 Ag after vaccination. A strong immune response was noted in 129 PwMS (36.5%). The rate of seroconversion after SARS-CoV-2 vaccination in PwMS who received immunomodulatory DMTs (interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab) was 91.5%, in PwMS receiving immune reconstruction therapy (alemtuzumab, cladribine) was 92%, and in immunosuppressive DMTs (fingolimod, ocrelizumab), the seroconversion rate was 59%.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Our study shows that, in PwMS receiving immunomodulatory therapy, the immune response to vaccination is generally excellent. Even in immunosuppressive patients, seroconversion is satisfactory.
Topics: Female; Male; Humans; Multiple Sclerosis; Poland; COVID-19 Vaccines; Seroconversion; COVID-19; SARS-CoV-2; Immunosuppressive Agents
PubMed: 38251955
DOI: 10.5603/pjnns.96425 -
Patient Preference and Adherence 2024Multiple sclerosis (MS) is a neurodegenerative disease characterized by progressive deterioration of cognitive and physical functioning, reducing activities of daily...
INTRODUCTION
Multiple sclerosis (MS) is a neurodegenerative disease characterized by progressive deterioration of cognitive and physical functioning, reducing activities of daily living and quality of life (QoL). Several treatments are available that modify the course of the disease and reduce the frequency of relapses. Although effective, all treatment options are accompanied by adverse events, and this study aimed to assess the extent to which patients were involved in the choice of treatment.
METHODS
Data were drawn from the Adelphi Multiple Sclerosis Disease Specific Program (DSP)™, a cross-sectional survey of healthcare practitioners (HCP) and their patients with MS in real-world clinical settings in Europe and the United States (US) between December 2020 and July 2021. HCPs reported patient demographics, clinical characteristics, current and previous treatment, and treatment outcomes. Patients voluntarily completed questionnaires reporting the physical and psychological impact of their MS and its treatment. Regression analysis with inverse probability of treatment weighting was used to compare treatment outcomes in patients actively involved in their current treatment choice with those who were not.
RESULTS
Of a total of 692 patients, median age 40 years and 64% female, mostly diagnosed with relapsing-remitting MS, those who were involved in shared decision-making tended to choose oral therapies such as dimethyl fumarate more often than HCPs. MS had greater impact on physical and psychological functioning in patients whose HCP made treatment decisions solely. Patients involved in decision-making reported greater satisfaction with their treatment and a better QoL.
DISCUSSION
Because no single optimal therapy exists for patients with MS, treatments should be individualized with consideration of patients' preferences. Our study shows that shared decision-making is under-utilized in the management of MS and supports the benefits of patient involvement.
CONCLUSION
Patients who have an active role in treatment decision-making show improved wellbeing and QoL, and overall treatment satisfaction.
PubMed: 38249686
DOI: 10.2147/PPA.S440410 -
Neurotherapeutics : the Journal of the... Mar 2024Disease-modifying therapies (DMTs) can affect vaccine responses in individuals with multiple sclerosis (MS). We assessed the humoral and T-cell responses following...
Disease-modifying therapies (DMTs) can affect vaccine responses in individuals with multiple sclerosis (MS). We assessed the humoral and T-cell responses following SARS-CoV-2 mRNA vaccination in MS patients receiving various DMTs. We prospectively enrolled 243 participants, including 113 healthy control subjects and 130 MS patients. Blood samples for detecting SARS-CoV-2 antibodies were collected at three time points: T0, before the first vaccine dose; T1, before the second dose; and T2, one month after the second dose. In a subgroup of 51 patients and 20 controls, samples were collected at T0 and T2 to assess the T-cell immune response to the Spike antigen of SARS-CoV-2 using ELISPOT-IFNγ. The IgG levels in patients treated with fingolimod and ocrelizumab (159.1 AU/ml and 467.1 AU/ml, respectively) were significantly lower than those in healthy controls and patients on other DMTs (P < 0.0001). The mean Ig titers were higher in patients with an absolute lymphocyte count ≥1000 cells/mm3 compared to those with a count between 500 and 1000 and with a count <500 (mean ± SD:7205.6 ± 7339.2, 2413.1 ± 4515.4 and 165.9 ± 152.2, respectively; p = 0.008). We found correlations between antibody levels and age (r = 0.233, p = 0.008). A positive Spike-specific T-cell response was detectable in 100 % of vaccinated healthy controls and patients treated with teriflunomide, dimethyl-fumarate, and natalizumab, in 90.5 % of fingolimod patients, and in 63.8 % of ocrelizumab patients. There is a correlation between IgG-specific titer after SARS-CoV-2 vaccination and clinical variables (age, lymphocyte count). Notably, a T-cell-specific response to SARS-CoV-2 developed in patients treated with fingolimod and ocrelizumab, even with lower rates of humoral response.
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; Multiple Sclerosis; mRNA Vaccines; Fingolimod Hydrochloride; COVID-19; T-Lymphocytes; Immunoglobulin G; Vaccination
PubMed: 38237381
DOI: 10.1016/j.neurot.2023.e00307 -
Brain Communications 2024Fingolimod is a frequently used disease-modifying therapy in relapsing-remitting multiple sclerosis. However, case reports and small observational studies indicate a...
Fingolimod is a frequently used disease-modifying therapy in relapsing-remitting multiple sclerosis. However, case reports and small observational studies indicate a highly increased risk of disease reactivation after discontinuation. We aimed to investigate the risk of radiological disease reactivation in patients discontinuing fingolimod. We performed a nationwide cohort study in Denmark, including patients who discontinued fingolimod between January 2014 and January 2023. Eligibility was a diagnosis with relapsing-remitting multiple sclerosis and two MRIs performed respectively within 1 year before and after discontinuing fingolimod. The included patients were compared with those discontinuing dimethyl fumarate with the same eligibility criteria in an unadjusted and matched propensity score analysis. Matching was done on age, sex, Expanded Disability Status Scale, MRI data, cause for treatment discontinuation, treatment duration and relapse rate. The main outcome was the presence of new T lesions on the first MRI after treatment discontinuation. To identify high-risk patients among those discontinuing fingolimod, we made a predictive model assessing risk factors for obtaining new T lesions. Of 1324 patients discontinuing fingolimod in the study period, 752 were eligible for inclusion [mean age (standard deviation), years, 41 (10); 552 females (73%); median Expanded Disability Status Scale (Q1-Q3), 2.5 (2.0-3.5); mean disease duration (standard deviation), years, 12 (8)]. Of 2044 patients discontinuing dimethyl fumarate in the study period, 957 were eligible for inclusion, presenting similar baseline characteristics. Among patients discontinuing fingolimod, 127 (17%) had 1-2 new T lesions, and 124 (17%) had ≥3 new T lesions compared with 114 (12%) and 45 (5%), respectively, for those discontinuing dimethyl fumarate, corresponding to odds ratios (95% confidence interval) of 1.8 (1.3-2.3) and 4.4 (3.1-6.3). The predictive model, including 509 of the 752 patients discontinuing fingolimod, showed a highly increased risk of new T lesions among those with disease activity during fingolimod treatment and among females under 40 years. This nationwide study suggests that discontinuing fingolimod in some cases carries a risk of developing new T lesions, emphasizing the importance of clinical awareness. If feasible, clinicians should prioritize the prompt initiation of new disease-modifying therapies, particularly among young females.
PubMed: 38214014
DOI: 10.1093/braincomms/fcad358