Biologic Therapy For Ocular Inflammatory Diseases: An Update

Mesquida M,Adan A

doi:10.19070/2332-290x-130001

Abstract

Uveitis comprehends a wide and heterogeneous group of intraocular inflammatory conditions potentially sight-threatening and vari - able therapeutic strategies have been proposed. Classical treatment with steroids and conventional immunosuppressive agents is often used as first-step. However, a number of patients may not respond properly or tolerate these medications with well-known side ef - fects. Over the last two decades, advances in the understanding of the pathogenesis of autoimmune uveitis, as well as improved bio- technology, have enabled the development of a new class of drugs called biologics, which provide selective targeting of the immune mediators of the inflammation cascade. Biologic therapies were introduced as a new option for patients with autoimmune rheumatic conditions refractory to conventional therapy and due to their success have posteriorly been used in ophthalmology to treat ocular inflammatory disorders. These new agents may potentially provide more effective and less toxic treatment than conventional therapy. Biologic therapies include a wide variety of drugs with different mechanisms of action, including monoclonal antibodies against cell surface markers, cytokines and their receptors, or recombinant forms of natural inhibitory molecules. Although some results are based on investigations with insufficient clinical trials, the majority of biologics indicate preferable outcomes on refractory uveitis, with remarkable promise to increase the possibility of long-term remission. The development of these new drugs is one of the most revo- lutionary advances in recent years, and the promise of shifting paradigms makes it an exciting time for uveitis specialists worldwide.

Highlights

Uveitis is a major cause of severe visual impairment that accounts for 10–15% of all cases of total blindness in the US, and one of the major causes of visual handicap within the working population worldwide[1]
Biologics include a wide variety of drugs with different mechanisms of action, including monoclonal antibodies against cell surface markers, cytokines and their receptors, or recombinant forms of natural inhibitory molecules
In addition there is a strong heterogeneity of the study variables. Another limitation is the variability of the uveitis etiologies among the patients included in most of the studies

Summary

Introduction

Uveitis is a major cause of severe visual impairment that accounts for 10–15% of all cases of total blindness in the US, and one of the major causes of visual handicap within the working population worldwide[1]. It has been used to treat a wide variety of autoinflammatory conditions, including chronic infantile neurological cutaneous articular syndrome (CINCA)associated uveitis refractory to anti-TNF therapy, confirming the success in the preclinical experimental autoimmune uveitis model in mice [66] Serious infections such as pneumonia and infectious cellulitis seem more frequent with anakinra, there is no increased risk of tuberculosis. Our group recently reported two papers studying the efficacy of tocilizumab infusions in uveitis cases with severe cystoid macular edema refractory to systemic and local treatments [85,86]. There is emerging data demonstrating efficacy in the setting of recalcitrant Juvenile Idiopathic Arthritis- associated uveitis that has failed traditional immune modulation or TNF Inhibitors [92] It is administered with a 30-minutes slow intravenous infusion, given every 2 weeks for the first 3 doses and every 4 weeks. It is currently under investigation in phase II trials for the treatment of uveitis (NCT01279954)

Other Emerging Therapies

Findings

Discussion