Are biologics safe in the treatment of atopic dermatitis? A review with a focus on immediate hypersensitivity reactions

Bremmer, Matthew; Bremmer, Samuel; Baig-Lewis, Shahana; Simpson, Eric L.

doi:10.1016/j.jaad.2009.02.041

Cited by 18 publications

(14 citation statements)

References 59 publications

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“…2 However, possible long-term side effects of these biologics are unknown, 116 and biologics still are relatively expensive. Clinicians will have to evaluate the risks, benefits, and costs accordingly.…”

Section: Improving the Performance Of Immunosuppressive Drugs Using Pmentioning

confidence: 99%

Biomarkers for atopic dermatitis

Thijs

Krastev

Weidinger

et al. 2015

Current Opinion in Allergy &Amp; Clinical Immunology

199

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Section: Improving the Performance Of Immunosuppressive Drugs Using Pmentioning

confidence: 99%

Biomarkers for atopic dermatitis

Thijs

Krastev

Weidinger

et al. 2015

Current Opinion in Allergy &Amp; Clinical Immunology

199

View full text Add to dashboard Cite

“…Documented antidrug IgE resulting in anaphylaxis has been observed with numerous biotherapeutics in cynomolgus monkeys and humans (Abramowicz, Crusiaux, and Goldman 1992;Baudouin et al 2003;Bremmer et al 2009;Chung et al 2008;Cox 2009;Dietrich et al 2001;O'Neil et al 2007;Werner, personal communication, 2012). Hypersensitivity due to antidrug IgE is considered to be less common than that due to IgG (Calogiuri et al 2008).…”

Section: Hypersensitivity Reactionsmentioning

confidence: 99%

Unexpected Hematologic Effects of Biotherapeutics in Nonclinical Species and in Humans

Everds

Tarrant²

2013

Toxicol Pathol

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Biotherapeutics are expanding the arsenal of therapeutics available for treating and preventing disease. Although initially thought to have limited side effects due to the specificity of their binding, these drugs have now been shown to have potential for adverse drug reactions including effects on peripheral blood cell counts or function. Hematotoxicity caused by a biotherapeutic can be directly related to the activity of the biotherapeutic or can be indirect and due to autoimmunity, biological cascades, antidrug antibodies, or other immune system responses. Biotherapeutics can cause hematotoxicity primarily as a result of cellular activation, cytotoxicity, drug-dependent and independent immune responses, and sequelae from initiating cytokine and complement cascades. The underlying pathogenesis of biotherapeutic-induced hematotoxicity often is poorly understood. Nonclinical studies have generally predicted clinical hematotoxicity for recombinant cytokines and growth factors. However, most hematologic liabilities of biotherapeutics are not based on drug class but are species specific, immune-mediated, and of low incidence. Despite the potential for unexpected hematologic toxicity, the risk-benefit profile of most biotherapeutics is favorable; hematologic effects are readily monitorable and managed by dose modification, drug withdrawal, and/or therapeutic intervention. This article reviews examples of biotherapeutics that have unexpected hematotoxicity in nonclinical or clinical studies.

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“…Biologic agents are produced by living systems and are protein-based therapies including soluble receptors, monoclonal antibodies, or cytokines designed to modulate the immune response 113. Generally indicated for treatment of autoimmune inflammatory diseases such as rheumatoid arthritis, Crohn disease, psoriatic arthritis and moderate-to-severe plaque psoriasis, injected “biologic” agents have been tested off-label as a potential therapy for severe AD.…”

Section: Systemic Therapies: Overviewmentioning

confidence: 99%

“…The role played by IgE in AD is unclear, with limited data to support this molecule as a major pathogenic effector 113. In a literature review, Flohr et al estimated that only a third of patients with AD show true IgE sensitization 134.…”

Section: Systemic Therapies: Overviewmentioning

confidence: 99%

“…Binding of rituximab to its ligand induces cell lysis. It has been proposed that the complex immune dysregulation of AD may involve B cells directly or indirectly 113. Six patients with severe atopic eczema received rituximab (1 g intravenous, two doses separated by two weeks) and all showed clinical improvement within 4 to 8 weeks 142…”

Section: Systemic Therapies: Overviewmentioning

confidence: 99%

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Update on the management of chronic eczema: new approaches and emerging treatment options

Walling¹

2010

CCID

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Atopic dermatitis (AD) is a common disease with worldwide prevalence, affecting up to 20% of children and 3% of adults. Recent evidence regarding pathogenesis has implicated epidermal barrier defects deriving from filagrin mutations with resulting secondary inflammation. In this report, the authors comprehensively review the literature on atopic dermatitis therapy, including topical and systemic options. Most cases of AD will benefit from emollients to enhance the barrier function of skin. Topical corticosteroids are first-line therapy for most cases of AD. Topical calcineurin inhibitors (tacrolimus ointment, pimecrolimus cream) are considered second line therapy. Several novel barrier-enhancing prescription creams are also available. Moderate to severe cases inadequately controlled with topical therapy may require phototherapy or systemic therapy. The most commonly employed phototherapy modalites are narrow-band UVB, broadband UVB, and UVA1. Traditional systemic therapies include short-term corticosteroids, cyclosporine (considered to be the gold standard), methotrexate, azathioprine, mycophenolate mofetil, and most recently leflunamide. Biologic therapies include recombinant monoclonal antibodies acting on the immunoglobulin E / interleukin-5 pathway (omalizumab, mepolizumab), acting as tumor necrosis factor-α inhibitors (infliximab, etanercept, adalimumab), and acting as T-cell (alefacept) and B-cell (rituxumab) inhibitors, as well as interferon γ and intravenous immunoglobulin. Efficacy, safety, and tolerability are reviewed for each medication.

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Are biologics safe in the treatment of atopic dermatitis? A review with a focus on immediate hypersensitivity reactions

Cited by 18 publications

References 59 publications

Biomarkers for atopic dermatitis

Biomarkers for atopic dermatitis

Unexpected Hematologic Effects of Biotherapeutics in Nonclinical Species and in Humans

Update on the management of chronic eczema: new approaches and emerging treatment options

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