Biologic agents in experimental autoimmune uveitis

Giuliari, Gian Paolo; Sadaka, Ama; Hinkle, David M.

doi:10.1007/s10792-013-9756-0

Cited by 5 publications

(2 citation statements)

References 113 publications

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“…Corticosteroids are the mainstay of therapy, however, these drugs are often incapable of proper inflammation control and have long-term systemic side effects (7, 8). When inflammation is not controlled by corticosteroids or side effects are intolerable, systemic immunomodulatory therapy (IMT) should be considered (5, 9). Current IMT includes the inhibition of TNF, achieved with mAb, such as infliximab, adalimumab, golimumab, and certolizumab-pegol, or with receptor fusion protein (FP), etanercept (9, 10).…”

Section: Introductionmentioning

confidence: 99%

Anti-TNF Drugs for Chronic Uveitis in Adults—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2019

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Background: We aimed to assess efficacy and safety of anti-tumor necrosis factor (TNF) drugs for adult chronic non-infectious uveitis (NIU). Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysis of efficacy analysis was not performed due to significant clinical heterogeneity between studies' population and interventions. Results: A total of 1,157 references were considered and 3 studies were included. The overall risk of bias was moderate. In active NIU, adalimumab group showed an increased likelihood of VA preservation (risk ratio (RR) 1.75, 95%CI 1.32 to 2.32, n = 217), whereas the etanercept group did not (RR 0.81, 95%CI 0.57 to 1.14, n = 20). In inactive NIU, adalimumab was associated with increased likelihood of VA preservation (RR 1.31, 95%CI 1.12 to 1.53, n = 226). The rate of adverse events did not differ between anti-TNF and control arms (RR 1.03, 95%CI 0.94 to 1.13, n = 410). Conclusions: There is high quality evidence that adalimumab decreases the risk of worsening VA in active and inactive NIU and very low quality evidence that the risk of etanercept worsening VA in inactive NIU is not different from placebo. Moderate quality evidence suggests that anti-TNF agents are not different from placebo on the risk of study withdrawal.

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Section: Introductionmentioning

confidence: 99%

Anti-TNF Drugs for Chronic Uveitis in Adults—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

et al. 2019

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“…When inflammation is not well controlled by corticosteroids or side-effects are unacceptable or intolerable, systemic immunomodulatory therapy (IMT) should be considered. Current IMT options comprise the biologics, such as monoclonal antibodies (mAb) and fusion proteins (Pavesio et al 2010;Srivastava et al 2010;Giuliari et al 2014;Pasadhika & Rosenbaum 2014).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of intravitreal anti‐tumour necrosis factor drugs in adults with non‐infectious uveitis – a systematic review

Leal

Rodrigues

Sousa

et al. 2018

Acta Ophthalmologica

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Anti-tumour necrosis factor (TNF) drugs have been extensively used in non-infectious uveitis (NIU), when corticosteroids or conventional immunosuppressive drugs cannot adequately control inflammation or intolerable side-effects occur. However, systemic anti-TNF therapies are also associated with a myriad of side-effects. Therefore, intravitreal administration of anti-TNF biologics has been employed to minimize patient morbidity and systemic adverse effects, while maintaining therapeutic effectivity. We undertook a systematic review to determine evidence of efficacy and safety of intravitreal administration of anti-TNF drugs in adults with NIU. We conducted this systematic review according to the PRISMA guidelines. The protocol was registered with PROSPERO (CRD42016041946). We searched CENTRAL, MEDLINE and EMBASE, from inception to April 2017, as well as clinical trial registries and grey literature. The qualitative analysis included all studies of adult patients with a diagnosis of NIU and who received intravitreal anti-TNF drugs with a 4-week minimum follow-up. A total of 4840 references were considered for title and abstract screening. Seven full texts were screened, and five studies were considered for analysis. All studies were open-label, single-centre, prospective, non-randomized, interventional case series with a follow-up between 4 and 26 weeks, employing either adalimumab in two studies and infliximab in three. Three studies showed a treatment effect of anti-TNF intravitreal injections, while one study revealed short-term improvement and one study revealed no efficacy of anti-TNF intravitreal therapy. None of the studies reported ocular adverse effects but only two studies included electrophysiological assessment in the safety analysis and no study assessed systemic human anti-drug antibodies. The available evidence is not sufficiently robust to conclude about the clinical effectivity of intravitreal anti-TNF in NIU and so no recommendation can be made. In conclusion, intravitreal injection of anti-TNF antibodies remains a possible treatment option to be explored through robust clinical investigation.

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Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development

Salazar-Méndez¹,

Yilmaz²,

Cordero‐Coma

2015

Expert Opinion on Investigational Drugs

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Enhanced understanding of the pathogenic mechanisms leading to immune-mediated uveitis has led to the identification of new therapeutic targets and thus to the development of more specific drugs. In addition, considering that the eye is a semi-enclosed chamber and that local therapy has the benefit of sparing the rest of the body from potentially toxic exposure, several attempts of establishing direct ophthalmologic avenues for delivery of the established and emerging drugs have also been made. All these advances have been an unquestionable step forward in the challenging management of uveitis patients.

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Biologic agents in experimental autoimmune uveitis

Cited by 5 publications

References 113 publications

Anti-TNF Drugs for Chronic Uveitis in Adults—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Anti-TNF Drugs for Chronic Uveitis in Adults—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Efficacy and safety of intravitreal anti‐tumour necrosis factor drugs in adults with non‐infectious uveitis – a systematic review

Moving forward in uveitis therapy: preclinical to phase II clinical trial drug development

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