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

Abstract

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.

Uveitis Therapy With Shark Variable Novel Antigen Receptor Domains Targeting Tumor Necrosis Factor Alpha or Inducible T-Cell Costimulatory Ligand

“…Local immune suppression with corticosteroids has a well-established role in the treatment of noninfectious uveitis 13,55,56. Since therapy with systemic anti-TNFα agents is effective, the next reasonable question is whether there is benefit from local anti-TNFα therapy 57,58. A few cases of intravitreal infliximab59 and adalimumab60,61 injection in humans have been reported.…”

Miliary tuberculosis developing during adalimumab treatment for Behçet’s disease with uveitis

“…Intravitreal administration of anti-TNF biologics has been trialled to reduce systemic adverse events. However, a systematic review concluded there is insufficient evidence to support their use due to limited efficacy with only short-term improvement 23. Lastly, a phase III study has demonstrated the efficacy of intravitreal sirolimus for NIU of the posterior segment and is a potential future local treatment strategy 24–26…”

Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice

“…Intravitreal injections of 1, 1.5, and 2 mg of ADA in 4 mL of vitreous humour (0.2, 0.375, and 0.5 mg/mL) have been reported to be safe for humans. 32,33 Besides, we applied the formula for dose conversion between humans and mice (HED = NOAEL * Km ratio (for mice)) to select the highest concentration of ADA (4.61 mg/mL = 0.375 mg/ mL × 12.3). 34 To select the best effective dose the eyes of rd10 mice received a single intravitreal (ivt) dose of the following ADA concentrations: 0.125, 0.25, 0.375, 4.61 mg/ mL at P12.…”