Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions

Multiple sclerosis; SARS-COV-2 vaccination; Humoral immune responseEsclerosis múltiple; Vacunación SARS-COV-2; Respuesta inmune humoralEsclerosi múltiple; Vacunació SARS-COV-2; Resposta immune humoralBackground: The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. Methods: Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. Results: Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. Conclusion: Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was sponsored by Biogen (Cambridge, MA, USA). Funding for writing and editorial support was provided by Biogen

Associations of sNfL with clinico-radiological measures in a large MS population

Esclerosi múltiple; Cadena lleugera de neurofilaments sèricsEsclerosis múltiple; Cadena ligera de neurofilamentos séricosMultiple sclerosis; Serum neurofilament light chainObjective Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice. Methods Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay. Results Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with sNfL-E included male sex, younger age, progressive disease subtype, diabetes mellitus, impaired renal function, and active smoking. Higher body mass index (BMI) was associated with lower odds of elevated sNfL. Active treatment with disease-modifying therapy was associated with lower odds of sNfL-E. MS participants with sNfL-E exhibited worse neurological function (patient-reported disability, walking speed, manual dexterity, and cognitive processing speed), lower brain parenchymal fraction, and higher T2 lesion volume. Longitudinal analyses revealed accelerated short-term rates of whole brain atrophy in sNfL-E participants and higher odds of new T2 lesion development, although both MS participants with or without sNfL-E exhibited faster rates of whole brain atrophy compared to HC. Findings were consistent in analyses examining age-normative sNfL Z-scores as a continuous variable. Interpretation Elevated sNfL is associated with clinical disability, inflammatory disease activity, and whole brain atrophy in MS, but interpretation needs to account for comorbidities including impaired renal function, diabetes, and smoking.Study funding was provided from the National Institutes of Health (K23NS117883 to E.S.S.; K01MH121582 to K.C.F.; U01NS111678 to P.A.C.), National Multiple Sclerosis Society (RG-1904-33834 to E.S.S.; RG-1904-33800 to P.A.C.), and Biogen

Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions

The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs

Determining the effectiveness of early intensive versus escalation approaches for the treatment of relapsing-remitting multiple sclerosis: The DELIVER-MS study protocol

Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access

National Estimates of Pediatric Infectious Disease Hospitalizations from 1997-2009: An Analysis of the Kids\u27 Inpatient Database

Background. Infectious diseases are a major source of morbidity and mortality in children. In this study, we sought to identify and generate national estimates of the primary infectious disease diagnoses associated with pediatric hospitalizations. Methods. We analyzed a nationwide, stratified probability sample of hospital discharges among children \u3c18 years that was weighted using a complex survey design to 36.3 million discharges over a five year period, including: 1997, 2000, 2003, 2006, and 2009. Primary infectious disease discharge diagnoses were identified using the Clinical Classification Software and Major Diagnostic Categories, which were developed for use with the Healthcare Cost and Utilization Project (HCUP) Kids\u27 Inpatient Database. Results. Annually, 687,000 of 7.3 million (9.4%) pediatric discharges were associated with a primary infectious disease diagnosis. The proportion of pediatric hospitalizations with a primary infectious disease discharge diagnosis decreased from 11.2 to 8.8% from 1997 to 2009 (P \u3c 0.001). After newborn deliveries, infectious diseases were the leading cause of pediatric hospitalization. Eight conditions accounted for more than 80% of pediatric infectious disease discharge diagnoses (table). Respiratory tract infections accounted for 63% of all pediatric infectious disease hospitalizations. Conclusion. Infectious diseases are a leading cause of pediatric hospitalizations, led by pneumonia and bronchiolitis. Infectious disease diagnoses were the primary diagnosis for approximately 10% of all pediatric hospitalizations and a substantial proportion of health expenditures

National Estimates of Pediatric Infectious Disease Hospitalizations from 1997-2009: An Analysis of the Kids\u27 Inpatient Database

Background. Infectious diseases are a major source of morbidity and mortality in children. In this study, we sought to identify and generate national estimates of the primary infectious disease diagnoses associated with pediatric hospitalizations. Methods. We analyzed a nationwide, stratified probability sample of hospital discharges among children \u3c18 years that was weighted using a complex survey design to 36.3 million discharges over a five year period, including: 1997, 2000, 2003, 2006, and 2009. Primary infectious disease discharge diagnoses were identified using the Clinical Classification Software and Major Diagnostic Categories, which were developed for use with the Healthcare Cost and Utilization Project (HCUP) Kids\u27 Inpatient Database. Results. Annually, 687,000 of 7.3 million (9.4%) pediatric discharges were associated with a primary infectious disease diagnosis. The proportion of pediatric hospitalizations with a primary infectious disease discharge diagnosis decreased from 11.2 to 8.8% from 1997 to 2009 (P \u3c 0.001). After newborn deliveries, infectious diseases were the leading cause of pediatric hospitalization. Eight conditions accounted for more than 80% of pediatric infectious disease discharge diagnoses (table). Respiratory tract infections accounted for 63% of all pediatric infectious disease hospitalizations. Conclusion. Infectious diseases are a leading cause of pediatric hospitalizations, led by pneumonia and bronchiolitis. Infectious disease diagnoses were the primary diagnosis for approximately 10% of all pediatric hospitalizations and a substantial proportion of health expenditures

Characteristics of Antimicrobial Studies Registered in the USA Through Clinicaltrials.gov

Increasing rates of antimicrobial-resistant infections and the dwindling pipeline of new agents necessitate judicious, evidence-based antimicrobial prescribing. Clinical trials represent a vital resource for establishing evidence of safety and efficacy, which are crucial to guiding antimicrobial treatment decisions. The objective of this study was to comprehensively evaluate the characteristics of antimicrobial research studies registered in ClinicalTrials.gov. Primary outcome measures, funding sources, inclusion criteria and the reporting of study results were evaluated for 16 055 antimicrobial studies registered in ClinicalTrials.gov as of mid 2012. Interventional studies accounted for 93% of registered antimicrobial studies. Clinical trials of drugs (82%) and biologics (9%) were most common. Antibacterial, antiviral and antifungal studies accounted for 43%, 41% and 16% of drug trials, respectively. Among interventional drug trials, 73% featured randomised allocation to study arms and 71% included measures of safety and/or efficacy as primary endpoints. Children were eligible for enrolment in 26% of studies. Among the studies, 60% were sponsored primarily by non-profit organisations, 30% by industry and 10% by the federal government. Only 7% of studies reported results; however, 71% of these were sponsored primarily by industry. Antimicrobial studies commonly incorporated elements of high-quality trial design, including randomisation and safety/efficacy endpoints. Publication of study results and updating of ClinicalTrials.gov should be encouraged for all studies, with particular attention paid to research sponsored by non-profit organisations and governmental agencies. Leveraging the application of these data to guide the careful selection of antimicrobial agents will be essential to preserve their utility for years to come

Characteristics of Antimicrobial Studies Registered in the USA Through Clinicaltrials.gov

Increasing rates of antimicrobial-resistant infections and the dwindling pipeline of new agents necessitate judicious, evidence-based antimicrobial prescribing. Clinical trials represent a vital resource for establishing evidence of safety and efficacy, which are crucial to guiding antimicrobial treatment decisions. The objective of this study was to comprehensively evaluate the characteristics of antimicrobial research studies registered in ClinicalTrials.gov. Primary outcome measures, funding sources, inclusion criteria and the reporting of study results were evaluated for 16 055 antimicrobial studies registered in ClinicalTrials.gov as of mid 2012. Interventional studies accounted for 93% of registered antimicrobial studies. Clinical trials of drugs (82%) and biologics (9%) were most common. Antibacterial, antiviral and antifungal studies accounted for 43%, 41% and 16% of drug trials, respectively. Among interventional drug trials, 73% featured randomised allocation to study arms and 71% included measures of safety and/or efficacy as primary endpoints. Children were eligible for enrolment in 26% of studies. Among the studies, 60% were sponsored primarily by non-profit organisations, 30% by industry and 10% by the federal government. Only 7% of studies reported results; however, 71% of these were sponsored primarily by industry. Antimicrobial studies commonly incorporated elements of high-quality trial design, including randomisation and safety/efficacy endpoints. Publication of study results and updating of ClinicalTrials.gov should be encouraged for all studies, with particular attention paid to research sponsored by non-profit organisations and governmental agencies. Leveraging the application of these data to guide the careful selection of antimicrobial agents will be essential to preserve their utility for years to come