News Feature: a New Option for Uveitis
Adalimumab, a rheumatology drug, offers hope to patients with this damaging inflammatory eye disease.
There is no doubt that 2016 will be remembered as a year of innovations in pharmaceuticals for eye care, and there is also no doubt that patients will be the recipients of the benefits of these innovations. With the recent approval of adalimumab (Humira; AbbVie) for the treatment of uveitis, eye care providers now have an expanded therapeutic armamentarium for the management of this damaging inflammatory disease.
The FDA approved adalimumab in June for ophthalmic use in the treatment of noninfectious intermediate and posterior uveitis and panuveitis. A representative of the class of pharmaceutical agents targeting tumor necrosis factor α (TNF-α), this drug has a long, safe history in the treatment of several types of rheumatic diseases.1,2 Compared with other anti-TNF-α treatments, adalimumab has been noted to generate fewer adverse or allergic events, possibly because of the biochemical structure of the molecule.3 The additional indication in the field of ophthalmology for the treatment of uveitis follows other indications added in recent years for intestinal Behçet disease and severe ulcerative colitis.4
TNF-α is a pleiotropic or single-gene expression, multiple-cell origin cytokine that affects multiple systems and plays a leading role in the pathogenesis of uveitis. Interleukin 10 (IL-10) is an anti-inflammatory cytokine expressed by CD4+ T cells as a consequence of anti-TNF-α treatment that, together with down-regulation of macrophages, has been posited as the mechanism of action of many TNF-α–blocking drugs. It is thought that CD4+ T cell expression of IL-10 leads to the resolution of uveitis with anti-TNF-α treatment.1-3,5
Adalimumab has long been approved for use in adults with moderate to severe rheumatoid arthritis, severe active ankylosing spondylitis, moderate to severe chronic plaque psoriasis, and active or progressive psoriatic arthritis. The drug is also used in moderately to severely active Crohn disease, moderately to severely active ulcerative colitis, and moderately to severely active hidradenitis suppurativa. Indications in the pediatric population include active enthesitis-related arthritis, severe chronic plaque psoriasis, severely active Crohn disease, and active polyarticular juvenile idiopathic arthritis.6
The regulatory approval decision was based on the results of two phase 3 studies, VISUAL-I and VISUAL-II. Both studies were double masked and placebo controlled, and both enrolled adult patients with active and controlled noninfectious intermediate and posterior uveitis and panuveitis. Investigators found that patients who were treated with adalimumab had a statistically significantly lower risk for treatment failure than those receiving placebo. Treatment failure was defined as an increase in anterior chamber cells or vitreous haze, new chorioretinal or vascular lesions, or a decrease in visual acuity.1,7
1. Brezin AP, Kestelyn P, Van Calster J, et al. Adalimumab in patients with active, noninfectious uveitis using high-dose corticosteroids [abstract]. Arthritis Rheumatol. 2015;67(suppl 10).
2. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 1986;322:547-549.
3. Selmaj KW, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988;23:339-346.
4. New Drugs Approved in FY 2013. Pharmaceutical and Medical Devices Agency (PMDA) website. http://www.pmda.go.jp/files/000153463.pdf#page=1. Accessed July 11, 2016.
5. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.
6. Humira [package insert]. Chicago, IL: AbbVie Inc; 2016.
7. Sheppard JD, Joshi A, Mittal M, et al. Effect of adalimumab on visual functioning (VFQ-25) in VISUAL-1 trial patients with non-anterior non-infectious uveitis. Paper presented at: Association for Research in Vision and Ophthalmology; May 3-7, 2015; Denver, CO.
Agustin L. Gonzalez, OD
• optometric glaucoma specialist and therapeutic optometrist in practice at Eye & Vision in Richardson, Texas
• financial interest: none acknowledged