Clinical Effect of Neutralizing Antibodies to Interferon Beta That Persist Long After Cessation of Therapy for Multiple Sclerosis

Voort, L.F. van der

doi:10.1001/archneurol.2010.21

Cited by 34 publications

(20 citation statements)

References 26 publications

(16 reference statements)

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“…However, its clinical efficacy is limited and a proportion of patients ranging between 20% and 55% do not respond 26. The development of NAbs is one of the factors affecting the efficacy of IFNβ treatment27; these antibodies persist even years after cessation of IFNβ therapy 28. Therefore, the identification of predictive biomarkers of their appearance and their subsequent implementation in clinical practice would be useful for an individualised therapy and to ensure more rational provision of IFNβ therapy.…”

Section: Discussionmentioning

confidence: 99%

HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-β therapy in multiple sclerosis

et al. 2014

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Section: Discussionmentioning

confidence: 99%

HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-β therapy in multiple sclerosis

et al. 2014

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“…The persistence of neutralizing antibodies to IFN-β predicts clinically active disease (39), while an inhibited expression of CD49d antigens on T-cells may serve as a marker of treatment efficacy during the administration of with natalizumab, a monoclonal antibody to that molecule (40). Furthermore, the frequency of CD4 + CD25 + Treg cells expressing Foxp3 has recently been successfully used to assess the effects of IFN-β therapy (41,42).…”

Section: Monitoring and Assessment Of Treatment Effectsmentioning

confidence: 99%

Biomarkers for Multiple Sclerosis

Tomioka

Matsui

2014

Intern. Med.

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Magnetic resonance imaging has been shown to be a powerful tool for diagnosing multiple sclerosis (MS) and evaluating surrogate markers of the disease activity. However, biomarkers may provide more accurate information regarding ongoing immune responses leading to demyelination and treatment effects in MS patients. Although serum biomarkers are easily accessible, they do not provide clear-cut results, whereas cerebrospinal fluid (CSF) biomarkers provide unequivocal information, although samples cannot be repeatedly obtained. For diagnosis, the presence of oligoclonal IgG bands remains important. In addition, measuring the levels of adhesion molecules, matrix metalloproteinase-9 and complement regulator factor H in the serum and evaluating the proportion of Th1/Th2 cells in the blood may be clinically feasible for monitoring the disease activity. In CSF samples, increased IL-8, IL-12, IL-17, CCL3, CCL5 and CXCL10 levels indicate active disease, and the flow cytometry findings of CSF cells can be used to detect increases in Th1 and CD4 + CD25 + cells during relapse. Biomarkers closely linked to the disease activity may be informative of the pathogenesis of MS, while those associated with tissue damage or repair may be targets of new treatment strategies. Establishing the latter will be a primary point of research in the near future.

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“…The clinical efficacy in comparative randomized trials is summarized in Table 3. Meta-analyses show that IFNβ is associated with a significant effect on MS relapses and disability progression compared with placebo [38, 39]; however, the effect of IFNβ therapy on disability progression has been disputed, as a large-scale, retrospective study of prospectively collected data demonstrated that IFNβ was not associated with a reduction in disability progression [35–37]. A consideration relating to the efficacy of the IFNβ formulations is the potential for patients to produce neutralizing antibodies.…”

Section: Parenteral Therapiesmentioning

confidence: 99%

“…A consideration relating to the efficacy of the IFNβ formulations is the potential for patients to produce neutralizing antibodies. Although the role of neutralizing antibodies is not fully understood, it is thought that they lead to treatment resistance and can therefore reduce treatment efficacy over the long term [38, 39]. …”

Section: Parenteral Therapiesmentioning

confidence: 99%

Immunological Mechanism of Action and Clinical Profile of Disease-Modifying Treatments in Multiple Sclerosis

2014

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Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials.

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Clinical Effect of Neutralizing Antibodies to Interferon Beta That Persist Long After Cessation of Therapy for Multiple Sclerosis

Abstract: To confirm that neutralizing antibodies (NAb) to interferon beta can persist after therapy withdrawal and to evaluate whether persisting NAb are associated with a worse clinical disease course in multiple sclerosis (MS).

Cited by 34 publications

References 26 publications

HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-β therapy in multiple sclerosis

HLA alleles as biomarkers of high-titre neutralising antibodies to interferon-β therapy in multiple sclerosis

Biomarkers for Multiple Sclerosis

Immunological Mechanism of Action and Clinical Profile of Disease-Modifying Treatments in Multiple Sclerosis

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