Original articleSecukinumab in the Treatment of Noninfectious Uveitis: Results of Three Randomized, Controlled Clinical Trials
Section snippets
Study Design and Patient Population
All of the studies were randomized, placebo-controlled, and double-masked, with study investigators and participants masked to treatment assignments. Informed consent was obtained from all patients in each study. Approvals from the institutional review boards at the participating centers were obtained, and the studies were conducted in accordance with the principles of the Declaration of Helsinki. The study details were registered on ClinicalTrials.gov (NCT00995709 [SHIELD], NCT01095250
Patient Demographics and Baseline Characteristics
In the SHIELD study, the majority of patients were male and aged <40 years. No major differences among treatment groups were observed with respect to demographics or baseline characteristics (Table 1, available at http://aaojournal.org). A total of 118 patients were randomized, of whom 97 (82.2%) completed the study and 21 (17.8%) discontinued the study. The most common reasons for discontinuation were AEs in the secukinumab 300 mg q2w group (n = 4, 10.3%), withdrawn consent in the secukinumab
Discussion
In 2010, Hueber et al23 reported that secukinumab demonstrated efficacy and safety in 16 patients with active chronic noninfectious uveitis who participated in an open-label proof-of-concept clinical study. In that study, disease severity in the participants with uveitis was comparable to that in a study of infliximab, an antibody to tumor necrosis factor-alpha (TNF-α), suggesting that inhibition of IL-17A also could be a valid therapeutic approach that warranted further investigation in
Acknowledgments
Manuscript writing was provided by Rupendra Jadhav and Damanjeet Ghai of Novartis Pharma AG. Editorial review was provided by Kalyan Pulipaka of Novartis Pharma AG and by Eric Justice and Andrew Horgan of BioScience Communications, New York, New York (supported by Novartis Pharma).
References (42)
- et al.
Incidence and prevalence of uveitis in Northern California: the Northern California Epidemiology of Uveitis Study
Ophthalmology
(2004) Current concepts in the etiology and treatment of Behçet disease
Surv Ophthalmol
(2005)- et al.
Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis
Am J Pathol
(2008) - et al.
Interleukin-17 family members and inflammation
Immunity
(2004) - et al.
Critical regulation of early Th17 cell differentiation by interleukin-1 signaling
Immunity
(2009) - et al.
Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity
Immunity
(2009) - et al.
Critical role of IL-21 in modulating TH17 and regulatory T cells in Behçet disease
J Allergy Clin Immunol
(2011) - et al.
Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E
Immunity
(2011) - et al.
General principles for the treatment of non-infectious uveitis
Inflamm Allergy Drug Targets
(2009) - et al.
Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation
Eye (Lond)
(2012)
The natural history of uveitis
Int Ophthalmol
The possible impact of uveitis in blindness: a literature survey
Br J Ophthalmol
The reported demography and causes of blindness throughout the world
Adv Ophthalmol
Behçet's syndrome
Curr Rheumatol Rep
Ocular features of Behçet's disease: an international collaborative study
Br J Ophthalmol
The role of T cells in autoimmune uveitis
Ocul Immunol Inflamm
Increased expression of interleukin 17 in inflammatory bowel disease
Gut
The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models
Arthritis Res Ther
Cytokine profile in Behçet's disease patientsRelationship with disease activity
Scand J Rheumatol
Upregulated IL-23 and IL-17 in Behçet patients with active uveitis
Invest Ophthalmol Vis Sci
TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1
Nat Med
Cited by (281)
Targeted therapies for uveitis in spondyloarthritis: A narrative review
2024, Joint Bone SpineUpdate on the systemic management of noninfectious uveitis in children and adolescents
2024, Survey of OphthalmologyRisk factors, clinical features and treatment of Behçet's disease uveitis
2023, Progress in Retinal and Eye ResearchSER recommendations for the treatment of uveitis
2023, Reumatologia ClinicaBehçet's disease uveitis
2023, Revue de Medecine InternePharmacologic Treatment Strategies in Psoriatic Arthritis
2023, Clinical Therapeutics
Manuscript no. 2012-1018.
Financial Disclosure(s): The author(s) have made the following disclosure(s): ADD has received compensation from Novartis for consultancy and work related to the conduct of the studies reported. ADD has also received research grants from Novartis. IT-T has received compensation from Novartis for travel, meetings, and accommodations related to the studies reported and other activities. SF has received compensation from Novartis for consultancy. SF has also received research grants from Novartis. M.Z. and S.A. have no financial relationships with Novartis. SHML and VB are employees of Novartis. Clinical trials.gov registration numbers: NCT00995709 (SHIELD), NCT01095250 (INSURE), and NCT01032915 (ENDURE).
The sponsor participated in the design of each study, conducting each study, data collection, data management, data analysis, interpretation of the data, and preparation and review of the manuscript.