Biologics for the treatment of noninfectious uveitis.

In this issue, we have two case-reports and a special report about the use of biologics in the treatment of noninfectious uveitis. Uveitis is one of the leading causes of blindness in the world. The pathogenesis of uveitis is classified into two groups: infectious and noninfectious. Treatment for infectious uveitis should be pathogen specific. Noninfectious uveitis should be treated with anti-inflammatory agents, in which corticosteroid is the mainstay. However, long-term use of moderate-to-large dose of corticosteroid is associated with various adverse effects. Immunomodulatory treatment (IMT) and biologics are used for corticosteroid sparing.

In Taiwan, the most difficult noninfectious is panuveitis associated with Behcet's disease and idiopathic retinal vasculitis, followed by juvenile idiopathic iridocyclitis. For uveitis with Behcet's disease, a significant portion of patients has guarded prognosis when treated only with corticosteroid or along with IMT. Infliximab, one of the tumor necrosis factor alpha inhibitors, is off-label used in Japan for Behcet's uveitis with good results.[12] However, infliximab was not approved in Taiwan due to the concern of tuberculosis. The VISUAL I[3] and VISUAL II[4] studies showed that the efficacy of Adalimumab in treating nonanterior noninfectious uveitis (NANIU). Adalimumab got the approval of the indication of NANIU in the USA, EU, and Japan in 2016, and in Taiwan, in 2017. A special report on the recommendation of the use of biologics is proposed by a group of uveitis subspecialists in Taiwan. This report is based on thorough review[56] of the previous guidelines in treating uveitis, especially those with strong evidence basis, and take special consideration of regional, ethnical, and socioeconomic variations. However, several points in addition should be mentioned as the followings:

Anti-TNF alpha and other biologics are associated with some adverse effects, especially the increased susceptibility to tuberculosis[7] and increased risk of reactivation of hepatitis virus B,[8] which should be monitored with the Risk-Management Plan, suggested by rheumatologists in Taiwan.

Since steroid is still the mainstay of the treatment of uveitis. Steroid responder is another reason for using steroid-sparing agents, and hence IMT and/or biologics, in earlier stage of the disease.

Most of the anterior uveitis could be controlled with topical or periocular treatment, mainly corticosteroid, as mentioned in the Special Report. Adalimumab got the indication of NANIU. However, chronic “anterior” uveitis associated with Juvenile idiopathic arthritis[9] and psoriatic arthritis are exceptional. They are chronic uveitis. Long-term use of systemic immunomodulatory is frequently indicated. Some of them could not be adequately controlled even with the use of IMT. In this condition, biologics may also play a role. In uveitis associated with psoriatic arthritis, biologics could be used under the indication of psoriasis or arthritis.[10] Since iridocyclitis in children could occur with absent or minimal activity of arthritis, we are looking forward to the approval of the indication of biologics for juvenile idiopathic iridocyclitis.[11]

There are a lot of variations in many aspects of uveitis such as disease entities, ethnical groups, and environmental factors. In Visual I and II studies, NANIU is regarded as a group.[12] When subgroups are examined, only the groups of idiopathic uveitis and birdshot chorioretinitis are of enough number of subjects for statistical analysis.[34] We believe that the response in other disease entities may not be all the same. Further studies are required for each noninfectious uveitis. However, the approval of the indication for NANIU may well give us one powerful weapon to combat the difficult battle against noninfectious uveitis with poor prognosis.[13]