Dataset Information

Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course.

ABSTRACT: Background:In multiple sclerosis (MS), the frequency of hypogammaglobulinemia is unknown. We aimed to evaluate the frequency of reduced immunoglobulin (Ig) concentrations and its association with immunotherapy and disease course in two independent MS cohorts. Methods:In our retrospective cross-sectional study, MS patients and control patients with head or neck pain from Bern University Hospital (Bern, Switzerland) and Eginition University Hospital (Athens, Greece) were included. The lower limits of normal (LLN) for serum Ig concentration were IgG < 700?mg/dl, IgM < 40?mg/dl, and IgA < 70?mg/dl. Mann-Whitney U test, analysis of variance test, and multiple linear regression analysis were employed. Results:In total, 327 MS patients were retrospectively identified (Bern/Athens: n?=?226/101). Serum IgG concentrations were frequently under LLN in both MS cohorts (Bern/Athens: 15.5%/14.9%), even when considering only untreated patients (Bern/Athens: 7.9%/8.6%). MS patients (n?=?327) were significantly more likely to have IgG concentrations below LLN and below 600?mg/dl in comparison with controls (n?=?58) (p?=?0.015 and 0.047, respectively). Between both patient groups, no significant differences were found in frequencies of IgA and IgM concentrations under LLN [n (MS patients/controls): IgA 203/30, IgM 224/24]. Independently of age, secondary progressive MS patients had lower IgG concentrations than relapsing-remitting and primary progressive patients (both: p???0.01). After adjusting for sex, age, and disease course, IgG concentrations were lower in patients treated with rituximab (p?=?0.001; n?=?42/327), intravenous corticosteroids (p?

SUBMITTER: Zoehner G

PROVIDER: S-EPMC6767745 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course.

Zoehner Greta G Miclea Andrei A Salmen Anke A Kamber Nicole N Diem Lara L Friedli Christoph C Bagnoud Maud M Ahmadi Farhad F Briner Myriam M Sédille-Mostafaie Nazanin N Kilidireas Constantinos C Stefanis Leonidas L Chan Andrew A Hoepner Robert R Evangelopoulos Maria Eleftheria ME

Therapeutic advances in neurological disorders 20190927

<h4>Background</h4>In multiple sclerosis (MS), the frequency of hypogammaglobulinemia is unknown. We aimed to evaluate the frequency of reduced immunoglobulin (Ig) concentrations and its association with immunotherapy and disease course in two independent MS cohorts.<h4>Methods</h4>In our retrospective cross-sectional study, MS patients and control patients with head or neck pain from Bern University Hospital (Bern, Switzerland) and Eginition University Hospital (Athens, Greece) were included. T ...[more]

PMID: 31632461

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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.

Project description:Background: Although disease-modifying therapies (DMTs) in multiple sclerosis (MS) are known to target the immune system, mechanisms of action, efficacy, safety, and tolerability profiles differ. The long-term impact of DMTs on the immune system and its relation to infectious complications is still poorly understood. Objectives: To analyze the effect of DMTs on serum immunoglobulin (Ig) levels under consideration of patient demographics and therapy duration. Design: We included 483 patients on DMTs, 69 patients without DMTs, and 51 controls in this retrospective cross-sectional study. Methods: IgG, IgM, and IgG subclass 1–4 levels of patients with MS under treatment with DMTs were compared with treatment naive MS patients and controls by multivariate linear regression. Further, Ig levels stratified by DMTs were analyzed regarding therapy duration. Results: MS patients treated with fingolimod (FG), natalizumab, and B-cell depleting therapies (BCDT) demonstrated significantly lower IgG and IgM levels than healthy controls after a median treatment of 37, 31, and 23 months, respectively (p < 0.05). Treatment with dimethyl fumarate (DMF) and teriflunomide was associated with lower IgG, but not IgM levels. DMF and BCDT were also associated with lower IgG1 levels, while FG led to a reduction of IgG2. Treatment with interferon-beta (IFN) and glatiramer acetate (GA) had no impact on Ig levels. Analysis of subgroups by linear regression also showed a time-dependent decrease of Igs levels in patients treated with BCDT with a median annual reduction of IgG of 3.2% and IgM of 6.2%. Conclusion: Treatment with DMTs, except GA and IFN, was associated with a decrease in Ig levels. DMTs differed in the extent of decreasing Ig levels but also in their differential effects on Ig subclasses. Monitoring of Ig levels should be considered in patients on long-term treatment with DMTs, particularly those on BCDT, to identify patients at risk of low immunoglobulin levels.

Dataset Information

Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course.

Publications

Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course.

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