Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

Friend, Susan; Richman, Sandra; Bloomgren, Gary; Cristiano, Lynda M.; Wenten, Madé

doi:10.1186/s12883-016-0674-4

Cited by 121 publications

(101 citation statements)

References 36 publications

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“…Several studies investigated the impact of exposure to interferon beta and/or glatiramer acetate, [144][145][146][147][148][149][150][151][152][153][154][155][156][157][158] while fewer and more recent ones explored the effect of natalizumab, [159][160][161] dimethyl fumarate, 162 teriflunomide 163 and fingolimod. 164 In most studies, women were classified as being exposed to a DMT, provided the last dose/injection of drug was administered after the last menstrual period before conception.…”

Section: Recommendationsmentioning

confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

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Section: Recommendationsmentioning

confidence: 99%

“…This issue resulted in a serious risk of bias 144,147,151,155 or a moderate risk of bias 145,152 in this domain. For the five cohort studies that included only an exposed group, three were rated as moderate quality 146,148,160 and two as poor quality 156,157 …”

Section: Exposure To Other Disease-modifying Treatmentsmentioning

confidence: 99%

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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“…The Tysabri Pregnancy Exposure Registry prospectively enrolled 369 patients with MS and seven patients with Crohn’s disease on natalizumab or with natalizumab exposure within 3 months of conception. Three-hundred and fifty five of the enrolled patients had known pregnancy outcomes 68. This observational study yielded a major birth defect rate of 5.05% (95% CI 2.9%–8.1%) in natalizumab-exposed patients, which was higher than that seen in the general population as calculated by the Metropolitan Atlanta Congenital Defects Program (MACDP), but no specific pattern of malformation was found.…”

Section: Natalizumab Safety and Tolerabilitymentioning

confidence: 78%

The use of natalizumab for multiple sclerosis

Brandstadter¹,

Sand²

2017

NDT

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Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing–remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability. The leading safety concern with natalizumab is its association with progressive multifocal leukoencephalopathy (PML), a rare brain infection typically seen only in severely immunocompromised patients caused by reactivation of the John Cunningham virus (JCV). Careful analysis of risk factors for PML in natalizumab-treated MS patients, specifi-cally the presence of anti-JCV antibodies, has led to risk mitigation strategies to improve safety. Additional biomarkers are under investigation to further aid risk stratification. Natalizumab’s high efficacy and favorable tolerability profile have led to a broad use by MS physicians, as both first-and second-line treatments. This review discusses the natalizumab efficacy, safety, and tolerability and finishes with pragmatic considerations regarding its use in clinical practice.

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“…111 In the CGRP therapeutics database in the public domain, there is a single report of a male birth of a galcanezumab-treated father on 300 mg with ankyloglossia, a birth defect that decreases mobility of the tip of the tongue, associated with a pathologically short, thick lingual frenulum. 114 Acute and long-term concerns exist regarding anti-drug antibodies and mAb bioconversion to toxic metabolites. 113 The multiple sclerosis global natalizumab Pregnancy Exposure Registry with 369 subjects reports the overall rate of birth defects as higher than that observed by the coding registry used, but without malformations that would suggest a drug effect, and the spontaneous abortion rate (9%) consistent with that of the general population.…”

Section: Anti-cgrp Mabs Pharmacokinetics: Complicating Issuesmentioning

confidence: 99%

CGRP, Amylin, Immunology, and Headache Medicine

Taylor

2018

Headache

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Background Calcitonin gene‐related peptide (CGRP) therapeutics introduce new excitement and possibly yet to be determined distressing discords in the field of Headache Medicine. Growth in knowledge of CGRP in the pathophysiology of migraine introduced CGRP antagonism to headache treatment. Potential adverse effects on the other circulatory and neurovascular diseases have been foremost concerns. Failures in development of gepants and growth in knowledge of monoclonal antibody therapeutics combined to deliver the anti‐CGRP monoclonal antibodies (mAbs). Current Situation as of July 2018 Erenumab, eptinezumab, fremanezumab, and galcanezumab are approved, submitted to, or preparing for submission at both the European Medicines Agency and the US Food and Drug Administration (FDA). Methods This Headache Currents update emanates from a symposium on CGRP and immunology in Headache Medicine, and reviews both. Results and Conclusion Understanding CGRP in Headache Medicine requires information on aspects of the CGRP ligand, cell surface G protein receptor, CGRP receptor specifics, and antagonism by CGRP small and large molecules. Recent reports of CGRP’s high affinity for amylin receptors dictate some attention to this family‐related peptide. To better understand potential immunogenic risks and off‐target toxicities of the anti‐CGRP monoclonal antibodies, this review discusses immunology and CGRP and reviews IgG structure and function, monoclonal antibody production, ligand–antigen–antibody relationships, and clinical CGRP mAb specifics. Upon completion, the reader should better summarize CGRP antagonist fundamentals, recall antibody structure and function, restate therapeutic mAbs attributes, and appraise immunogenic risks.

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Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study

Cited by 121 publications

References 36 publications

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

The use of natalizumab for multiple sclerosis

CGRP, Amylin, Immunology, and Headache Medicine

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