Efficacy and Safety of Intravenous Secukinumab in Noninfectious Uveitis Requiring Steroid-Sparing Immunosuppressive Therapy

Letko, Erik; Yeh, Steven; Foster, C. Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L.

doi:10.1016/j.ophtha.2014.12.033

Cited by 142 publications

(79 citation statements)

References 29 publications

(16 reference statements)

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“…Recent clinical trials of secukinumab, a fully human anti-IL-17A Ab, indicate its efficacy and safety for the treatment of chronic and active noninfectious uveitis that requires corticosteroid-sparing immunosuppressive therapy (48). In addition, mAb therapies for noninfectious uveitis to attenuate various inflammatory cytokines, including TNF-a, IL-1b, and IL-6, have been actively investigated in clinical trials (49).…”

Section: Discussionmentioning

confidence: 99%

Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses

Sakoda

Nagai

Murata

et al. 2016

The Journal of Immunology

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Herpesvirus entry mediator (HVEM), a member of the TNFR superfamily, serves as a unique molecular switch to mediate both stimulatory and inhibitory cosignals, depending on its functions as a receptor or ligand interacting with multiple binding partners. In this study, we explored the cosignaling functions of HVEM in experimental autoimmune uveitis (EAU), a mouse model resembling human autoimmune uveitis conditions such as ocular sarcoidosis and Behcet disease. Our studies revealed that EAU severity significantly decreased in HVEM-knockout mice compared with wild-type mice, suggesting that stimulatory cosignals from the HVEM receptor are predominant in EAU. Further studies elucidated that the HVEM cosignal plays an important role in the induction of both Th1- and Th17-type pathogenic T cells in EAU, including differentiation of IL-17–producing αβ+γδ− conventional CD4+ T cells. Mice lacking lymphotoxin-like, inducible expression, competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT), B- and T-lymphocyte attenuator (BTLA) or both LIGHT and BTLA are also less susceptible to EAU, indicating that LIGHT–HVEM and BTLA–HVEM interactions, two major molecular pathways mediating HVEM functions, are both important in determining EAU pathogenesis. Finally, blocking HVEM cosignals by antagonistic anti-HVEM Abs ameliorated EAU. Taken together, our studies revealed a novel function of the HVEM cosignaling molecule and its ligands in EAU pathogenesis through the induction of Th1- and Th17-type T cell responses and suggested that HVEM-related molecular pathways can be therapeutic targets in autoimmune uveitis.

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Section: Discussionmentioning

confidence: 99%

Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses

Sakoda

Nagai

Murata

et al. 2016

The Journal of Immunology

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“…[252] Intravenous dosing of secukinumab has shown greater efficacy than subcutaneous dosing in patients with non-infectious uveitis, suggesting that patients may not receive a sufficient amount of drug with subcutaneous administration. [253] Moreover, three multicenter, randomized, double-masked, phase III studies in the United States have examined the efficacy and safety of different doses of Secukinumab in patients with non-infectious uveitis. [254] Although the study suggested that secukinumab administration resulted in a beneficial effect and allowed for reduction of the use of concomitant immunosuppressive medication, the authors did not discover any dissimilarities in uveitis recurrence between placebo groups and secukinumab treatment groups.…”

Section: Ocular Diseasesmentioning

confidence: 99%

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Ratay

Bellotti

Gottardi³

et al. 2017

Adv Healthcare Materials

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Dry eye disease (DED), age-related macular degeneration (AMD), and Uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, pro-inflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies have been developed to either address the symptoms or abate the underlying cause of these diseases. Herein, we will review the challenges to deliver drugs to the relevant location in the eye for each of these diseases as well as current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment.

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“…Furthermore, patients with one of two eczemalike genodermatoses, namely the autosomal dominant variant of hyper-IgE syndrome due to STAT3 deficiency or STAT1 gain of function, have an impaired production of IL-17 and experience candidal and S. aureus infections [101]. Secukinumab is also being investigated as a treatment for rheumatoid arthritis (RA), psoriatic arthritis, multiple sclerosis, and uveitis [102][103][104][105][106].…”

Section: Anti-il-17amentioning

confidence: 99%

Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update

Wang

Beck

2016

Am J Clin Dermatol

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Atopic dermatitis is one of the most common chronic inflammatory skin diseases. It usually begins in childhood, has a considerable impact on patients' quality of life, and incurs substantial healthcare costs. The standard-of-care treatments for patients with moderate to severe disease are very limited and have variable and typically insufficient efficacy and many side effects, some of which are quite serious. However, over the last decade, considerable advances in our understanding of the pathogenesis of atopic dermatitis have paved the way for a number of new treatments. Most notable are the drugs that target the Th2-polarized immune system, which is thought to play a key role in many of the signs and symptoms characteristic of this disease. In this article, we briefly review the pathophysiology of atopic dermatitis, while noting that each patient's disease phenotype is likely due to a unique interplay of several disease-specific dysregulated pathways. Lastly, we cover emerging therapies for atopic dermatitis, focusing on those that target specific components of the immune system, which are altered in atopic dermatitis. The hope is that these new biologics or small-molecule antagonists, which have high specificity for their target molecules, will decrease the undesirable side effects caused by off-target effects commonly observed with current immunosuppressive agents that are characterized by broad biological actions.

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Efficacy and Safety of Intravenous Secukinumab in Noninfectious Uveitis Requiring Steroid-Sparing Immunosuppressive Therapy

Cited by 142 publications

References 29 publications

Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses

Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update

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