Immune Response to Seasonal Influenza Vaccine in Patients with Relapsing-Remitting Multiple Sclerosis Receiving Long-term Daclizumab Beta

Mehta, Lahar; Umans, Kimberly; Ozen, Gulden; Robinson, Randy R.; Elkins, Jacob

doi:10.7224/1537-2073.2016-026

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…Modulation of the IL-2 signal leads to selective antagonism of activated T cell responses and expansion of immunoregulatory CD56 bright NK cells [ 81 , 87 ] Fivefold expansion in CD56 bright NK cells at 1 year. Total lymphocyte, CD4 + and CD8 + T cell, and B cell counts decrease ≤10% from baseline during the first year of treatment [ 81 , 82 , 92 ] Effective immune responses to influenza vaccine [ 150 ] Pharmacodynamics are related to the half-life of daclizumab beta (21 days) and are reversible [ 55 , 81 , 82 ] Total lymphocyte counts return to baseline levels ~8–12 weeks after the last dose [ 81 , 82 ] Treg and CD56 bright NK cell numbers return to baseline levels within 24 weeks [ 81 , 93 , 95 ] Alemtuzumab (Lemtrada) Targets CD52 on lymphocytes and monocytes. It readily depletes B cells, T cells, monocytes, macrophages, and dendritic cells, leading to long-lasting changes in adaptive immunity, and reduces the pathogenesis of inflammatory response in MS [ 99 ] Decrease in the level of circulating T and B lymphocytes very rapidly, with the lowest values observed within days posttreatment [ 99 ] Lymphocytes repopulate within 8 months, but T cell populations take >1 year to fully repopulate [ 100 , 101 ] T cell populations do not recover to baseline levels [ 101 ] Natalizumab (Tysabri) Monoclonal antibody that selectively inhibits VLA-4 (α4β1) integrins, preventing leukocyte migration across the BBB [ 58 ] Increases the number of circulating leukocytes (including lymphocytes, monocytes, basophils, and eosinophils) [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations

Pardo

Jones

2017

J Neurol

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The treatment landscape for relapsing forms of multiple sclerosis (RMS) has expanded considerably over the last 10 years with the approval of multiple new disease-modifying therapies (DMTs), and others in late-stage clinical development. All DMTs for RMS are believed to reduce central nervous system immune-mediated inflammatory processes, which translate into demonstrable improvement in clinical and radiologic outcomes. However, some DMTs are associated with long-lasting effects on the immune system and/or serious adverse events, both of which may complicate the use of subsequent therapies. When customizing a treatment program, a benefit–risk assessment must consider multiple factors, including the efficacy of the DMT to reduce disease activity, the short- and long-term safety and immunologic profiles of each DMT, the criteria used to define switching treatment, and the risk tolerance of each patient. A comprehensive benefit–risk assessment can only be achieved by evaluating the immunologic, safety, and efficacy data for DMTs in the controlled clinical trial environment and the postmarketing clinical practice setting. This review is intended to help neurologists make informed decisions when treating RMS by summarizing the known data for each DMT and raising awareness of the multiple considerations involved in treating people with RMS throughout the entire course of their disease.

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Section: Introductionmentioning

confidence: 99%

The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations

Pardo

Jones

2017

J Neurol

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“…Although the differences between the groups were smaller and non-significant for an antigen-recall vaccination (tetanus toxoid booster dose), the fingolimod group did have a numerically lower proportion of responders [102]. A previous study with daclizumab, now withdrawn from the DMT market, also reported sufficient vaccinator response in an open-label single-arm extension study (termed SELECTED) [103]. The reported rate of seroconversion (from <10 hemagglutination inhibition titer to ≥40) was 69% for H1N1, 69% for H3N2, and 44% for B influenza strain [103].…”

Section: Vaccine Effectiveness In Multiple Sclerosismentioning

confidence: 93%

“…A previous study with daclizumab, now withdrawn from the DMT market, also reported sufficient vaccinator response in an open-label single-arm extension study (termed SELECTED) [103]. The reported rate of seroconversion (from <10 hemagglutination inhibition titer to ≥40) was 69% for H1N1, 69% for H3N2, and 44% for B influenza strain [103]. Although the study had a sufficient ratio of responders as per EMA/FDA criteria, the lack of control arm limits the ability in deriving final conclusions.…”

Section: Vaccine Effectiveness In Multiple Sclerosismentioning

confidence: 98%

“…Although the study had a sufficient ratio of responders as per EMA/FDA criteria, the lack of control arm limits the ability in deriving final conclusions. [103]. Other open-label, observational studies have utilized mixed patient populations which were treated with different DMTs and determined the overall influenza efficacy.…”

Section: Vaccine Effectiveness In Multiple Sclerosismentioning

confidence: 99%

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Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective

et al. 2020

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Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that is associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections, including the Epstein Bar virus (EBV) and human endogenous retroviruses (HERV). Furthermore, the fast development of immunomodulatory therapies further questions the efficacy of the standard immunization policies in MS patients. Topics reviewed: This narrative review will discuss the potential interplay between viral and bacterial infections and their treatment on MS susceptibility and disease progression. In addition, the review specifically discusses the interactions between MS pathophysiology and vaccination for hepatitis B, influenza, human papillomavirus, diphtheria, pertussis, and tetanus (DTP), and Bacillus Calmette-Guerin (BCG). Data regarding potential interaction between MS disease modifying treatment (DMT) and vaccine effectiveness is also reviewed. Moreover, HERV-targeted therapies such as GNbAC1 (temelimab), EBV-based vaccines for treatment of MS, and the current state regarding the development of T-cell and DNA vaccination are discussed. Lastly, a reviewing commentary on the recent 2019 American Academy of Neurology (AAN) practice recommendations regarding immunization and vaccine-preventable infections in the settings of MS is provided. Conclusion: There is currently no sufficient evidence to support associations between standard vaccination policies and increased risk of MS. MS patients treated with immunomodulatory therapies may have a lower benefit from viral and bacterial vaccination. Despite their historical underperformance, new efforts in creating MS-based vaccines are currently ongoing. MS vaccination programs follow the set back and slow recovery which is widely seen in other fields of medicine.

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“…A substudy of daclizumab-treated patients enrolled in SELECTED who received seasonal influenza vaccination achieved acceptable levels of serologic protection against the seasonal influenza and experienced no unique or worsened safety issues associated with vaccination. 136 …”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

Cohan

2016

BTT

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Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies.

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Immune Response to Seasonal Influenza Vaccine in Patients with Relapsing-Remitting Multiple Sclerosis Receiving Long-term Daclizumab Beta

Cited by 8 publications

References 17 publications

The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations

The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations

Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective

Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

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