Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis.
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ABSTRACT:
SUBMITTER: Schweitzer F
PROVIDER: S-EPMC8217029 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multiple sclerosis (MS) is a chronic and progressive neurological disease. MS is characterized by early-stage neuroinflammation, neurodegeneration, and demyelination, with a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. The currently unsatisfied availability of diagnostic and prognostic biomarkers concerning disease progression and treatment response represents an important requirement for therapy individualization and drug efficacy. Specific Disease Therapies (DMTs) are available to prevent MS-related brain damage; however, the specific drug choice is still under debate and needs further characterization. Since differentially expressed miRNAs have been proposed as diagnostic tools in neurodegenerative/neuro-inflammatory diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, we characterized the miRNA expression profiling in peripheral blood mononuclear cells (PBMC) of subjects with relapsing-remitting MS treated with high efficacy DMTs: Cladribine (CLA, n=11 patients) or Ocrelizumab (OCRE, n=14 patients). The treated patients were compared to control (CTR) untreated subjects (n=15). Blood samples were collected from patients before treatment (time t0) and 6 months post-treatment (time t1), but just once from control subjects. CLA drug tablets were administered to the selected relapsing-remitting MS patients with a dosage of 1.75 mg/kg given for 5 days. OCRE drug was administered to the other relapsing-remitting MS patients by infusion with a dosage of 300 mg, twice in two weeks.
2024-01-03 | GSE230064 | GEO
Project description:Multiple sclerosis (MS) is increasingly recognized in children and adolescents. Improved awareness, access to care, and subspecialty training in pediatric MS has allowed for better access to treatment. Children with MS present with an overwhelmingly relapsing form of the disease and have more frequent relapses than their adult counterparts during the early phases of disease. Cognitive deficits are prominent in pediatric MS, as opposed to locomotor disability. Beta interferons and glatiramer acetate are frequently used off-label drugs. Additional second-line therapies have occasionally been used in treatment failures. No randomized clinical trials have been performed to date in pediatric MS; however, recent legislation necessitates pediatric studies for new agents, which will allow for better defined pharmacokinetic, dosing, and efficacy data to guide the treating neurologist.
| S-EPMC3557355 | biostudies-literature
Project description:Multiple sclerosis (MS), a demyelinating disease of the central nervous system, was untreatable until the mid-1990s when beta-interferons and glatiramer acetate were introduced. These agents, while effective, were relatively nonspecific in action. Over the last 10 years, research has focused toward developing more targeted therapies for the disease. Monoclonal antibodies (mAbs) have been central to these efforts and many of the mAbs studied in MS have been singularly effective. We review here the 6 monoclonal antibodies that have been approved for MS or are in late-stage clinical trials, focusing on the drugs' efficacy and safety. Additionally, we review several monoclonal antibodies that were studied in MS but were found to be ineffective or even deleterious in this patient population.
| S-EPMC3967547 | biostudies-other
Project description:ObjectiveComorbidities are common in multiple sclerosis (MS) and adversely affect health outcomes. However, the effect of comorbidity on treatment decisions in MS remains unknown. We aimed to examine the effects of comorbidity on initiation of injectable disease-modifying therapies (DMTs) and on the choice of the initial DMT in MS.MethodsWe conducted a retrospective observational analysis using population-based health administrative and linked clinical databases in 3 Canadian provinces. MS cases were defined as any individual with ≥3 diagnostic codes for MS. Cohort entry (index date) was the first recorded demyelinating disease-related claim. The outcomes included choice of initial first-line DMTs and time to initiating a DMT. Logistic and Cox regression models were used to examine the association between comorbidity status and study outcomes, adjusting for sex, age, year of index date, and socioeconomic status. Meta-analysis was used to estimate overall effects across the 3 provinces.ResultsWe identified 10,698 persons with incident MS, half of whom had ≥1 comorbidities. As the total number of comorbidities increased, the likelihood of initiating a DMT decreased. Comorbid anxiety and ischemic heart disease were associated with reduced initiation of a DMT. However, patients with depression were 13% more likely to initiate a DMT compared to those without depression at the index date (adjusted hazard ratio 1.13; 95% confidence interval 1.00-1.27).ConclusionsComorbidities are associated with treatment decisions regarding DMTs in MS. A better understanding of the effects of comorbidity on effectiveness and safety of DMTs is needed.
| S-EPMC4826339 | biostudies-literature
Project description:ObjectiveDisease-modifying therapies (DMTs) can reduce multiple sclerosis (MS) relapse rates; however, effectiveness of treatments may vary. It is important to understand real-world treatment patterns in the context of MS relapses. We describe MS relapses related to treatment patterns among patients who switch treatment after their first DMT.MethodsIBM MarketScan research databases were used to identify adult patients with MS who switched DMTs (index-first switch) after being newly treated with a DMT from January 2009 through March 2017, with 12 months of continuous enrollment pre- and post-index. Non-persistence was defined as discontinuing (at least 60 days without DMT) or switching DMTs. MS relapses were defined using a validated claims-based algorithm. Multivariable analysis was used to examine odds of 12-month persistence, odds of post-index relapse, and number of relapses.ResultsIn total, 4121 patients with MS met all inclusion criteria (mean age 46.4 years; female 76.2%). Overall, 49.6% switched to an oral DMT, 36.5% to an injectable DMT, and 13.9% to an infusion DMT. Switching DMTs resulted in a 32.4% reduction in relapses between pre- and post-index. Only 54.6% of patients were persistent throughout the first year. Patients who switched to oral DMTs had 95% higher adjusted odds of persistence and 18% lower adjusted odds of a post-index period relapse than patients who switched to injectable DMTs. The number of baseline relapses was not associated with persistence but with 68% higher odds of a post-index relapse, with each additional baseline relapse associated with a 44% increase in number of post-index relapses.ConclusionsAmong patients with MS who switched DMTs, persistence was consistently low regardless of treatment. Although persistence with oral DMTs was slightly higher than with injectable DMTs, overall results indicate poor persistence to second-line therapy and highlight the need to improve long-term persistence with DMTs.
| S-EPMC7467407 | biostudies-literature
Project description:OBJECTIVE:To summarize major clinical trials which evaluate the efficacy and safety data of approved disease modifying agents for the treatment of various types of multiple sclerosis. DATA SOURCES:A MEDLINE (1966 to August 2008) search of clinical trials using the terms multiple sclerosis, interferon, glatiramer, mitoxantrone and natalizumab was performed. A manual bibliographic search was also conducted. English-language articles identified from the searches were evaluated. New agents under investigation in phase 3 clinical trials were identified using www.clinicaltrials.gov. STUDY SELECTION #ENTITYSTARTX00026; DATA EXTRACTION:Relevant information was identified and selected based on clinical relevance and evidence-based strength. Prescribing information leaflets were used to provide usual dosage, contraindications, precautions, monitoring parameters and other relevant drug-specific information. DATA SYNTHESIS:Interferon beta products are more efficacious for the treatment of relapsing-remitting multiple sclerosis. Interferon beta 1-b also delayed the time to diagnosis of definite multiple sclerosis and reduced brain lesion burden in patients with clinical isolated syndrome. Glatiramer and natalizumab have both established efficacy in relapsing forms of multiple sclerosis; whereas mitoxantrone is more commonly used in patients with advanced disease. There are limited data the comparative efficacy among different disease modifying agents. New agents currently under investigation have showed promising results and may offer more treatment options in the future. CONCLUSIONS:MS is a complex and devastating disease with challenging treatment considerations and approaches. Interferon beta products continue to be the mainstay of therapy in many patients, however, other treatments are proving to be at least as effective in the management of various types of MS. Newer compounds are being developed and studied with much anticipation and promise for the clinical management of the disease.
| S-EPMC3024587 | biostudies-other
Project description:BackgroundOver a dozen disease-modifying therapies (DMTs) have been approved for treatment of multiple sclerosis (MS). Treatment guidelines focus on when to initiate, change, and discontinue treatment but provide little guidance on how to select or sequence DMTs. This study assessed sequencing patterns of DMTs in patients with newly diagnosed MS.MethodsAdults newly diagnosed with MS in the United States were identified from January 2007 to October 2017 using IBM MarketScan database. Patients had ≥12 months of continuous enrollment prior to diagnosis and ≥ 2 years of follow-up. Treatment pathways consisting of up to 3 DMT courses were reported, and each treatment course ended with discontinuation, switch, or end of follow-up.ResultsIn total, 14,627 MS patients were treated with DMTs and had ≥2 years of follow-up. More than 400 DMT treatment pathways were observed. Glatiramer acetate was the most common DMT; 40% of patients initiated this treatment. Among these, 51.3% had 2 DMT courses during follow-up and 26.5% had 3 DMT courses. Approximately 70% of patients switched or discontinued their initial DMT, and rates of switch and discontinuation differed by initial DMT. Injectable DMTs were used most commonly over the study period (87.5% as first course to 66.6% as third course). Oral DMTs were more common as second or third treatment courses (29.9% and 31.8%, respectively).ConclusionsA wide variety in treatment patterns were observed among patients newly diagnosed with MS. Further examination of DMT prescribing practices is needed to understand the reasons behind treatment discontinuation and treatment cycling.
| S-EPMC9172015 | biostudies-literature
Project description:Multiple sclerosis (MS) is a chronic autoimmune disease that usually affects young adults, causing progressive physical and cognitive disability. Since the 1990s, its treatment has been based on parenteral medications known collectively as immunomodulators. This drug class is considered safe and usually prevents 30% of MS relapses. Drugs in this class exert almost the same efficacy and require an inconvenient administration route. New medications have recently been launched worldwide. Thus, new oral drugs are increasingly being administered to MS patients and contributing to a better quality of life, since these have better efficacy than the old immunomodulators. Today, 10 different drugs for MS are marketed worldwide, which requires deep knowledge among neurologists and other healthcare professionals. This paper summarizes all the drugs approved for MS in the US and Europe, emphasizing their mechanism of action, the results from phase II and III studies, and the product safety.
| S-EPMC4197902 | biostudies-other
Project description:BackgroundThere is currently limited literature addressing the reporting of alopecia in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs). Anecdotal reports of hair thinning from patients on various DMTs prompted further investigation of a large database.ObjectiveTo analyze total reports, source of reporting, age distribution, and sex distribution of alopecia associated with DMTs.MethodsFDA Adverse Event Reporting System (FAERS) public dashboard and OpenFDA database were analyzed for alopecia reports between January 1, 2009, and June 30, 2020, attributed to usage in MS of FDA approved DMTs. The main outcomes included total reports for each drug, age, sex distribution, and reporting source. OpenFDA data was used for statistical analyses including reporting odds ratios (ROR) and information components.Results8759 alopecia reports were identified among 44 114 adverse events in skin and subcutaneous tissue disorders (19.9%). 3701 (42.3%) with teriflunomide, 1675 (19.1%) with dimethyl fumarate, 985 (11.2%) with natalizumab, 926 (10.6%) with fingolimod, 659 (7.5%) with interferon beta-1a, 257 (2.9%) with glatiramer acetate, 243 (2.8%) with ocrelizumab, 124 (1.4%) with interferon beta-1b, 117 (1.3%) with alemtuzumab, 36 (.4%) with siponimod, 24 (.3%) with cladribine, and 12 (.1%) with rituximab. Reports were mostly made by patients (78.3%) and highest in fifth and sixth decades of life. OpenFDA analyses showed increased ROR (ROR 95% confidence interval) of alopecia in females with teriflunomide (18.00, 17.12-18.93), alemtuzumab (1.43, 1.16-1.76), dimethyl fumarate (1.26, 1.18-1.34), and ocrelizumab (1.28, 1.11-1.49). Increased ROR in males was associated with teriflunomide (24.65, 20.72-29.31).ConclusionWe identified many reports of alopecia for DMTs in addition to teriflunomide. Within the limitations of the database, increased RORs of alopecia were observed for females treated with alemtuzumab, dimethyl fumarate, and ocrelizumab. The source of reporting was largely driven by female patients. Possible alopecia, even if transient, should be considered during patient education when starting DMTs.
| S-EPMC9234852 | biostudies-literature
Project description:ObjectiveTo evaluate the association between health insurance coverage and disease-modifying therapy (DMT) use for multiple sclerosis (MS).MethodsIn 2014, we surveyed participants in the North American Research Committee on MS registry regarding health insurance coverage. We investigated associations between negative insurance change and (1) the type of insurance, (2) DMT use, (3) use of free/discounted drug programs, and (4) insurance challenges using multivariable logistic regressions.ResultsOf 6,662 respondents included in the analysis, 6,562 (98.5%) had health insurance, but 1,472 (22.1%) reported negative insurance change compared with 12 months earlier. Respondents with private insurance were more likely to report negative insurance change than any other insurance. Among respondents not taking DMTs, 6.1% cited insurance/financial concerns as the sole reason. Of respondents taking DMTs, 24.7% partially or completely relied on support from free/discounted drug programs. Of respondents obtaining DMTs through insurance, 3.3% experienced initial insurance denial of DMT use, 2.3% encountered insurance denial of DMT switches, and 1.6% skipped or split doses because of increased copay. For respondents with relapsing-remitting MS, negative insurance change increased their odds of not taking DMTs (odds ratio [OR] 1.50; 1.16-1.93), using free/discounted drug programs for DMTs (OR 1.89; 1.40-2.57), and encountering insurance challenges (OR 2.48; 1.64-3.76).ConclusionsInsurance coverage affects DMT use for persons with MS, and use of free/discounted drug programs is substantial and makes economic analysis that ignores these supplements potentially inaccurate. The rising costs of drugs and changing insurance coverage adversely affect access to treatment for persons with MS.
| S-EPMC4977112 | biostudies-literature