Infliximab (brand name: Remicade®) is a mouse/human chimeric monoclonal antibody that specifically binds to tumor necrosis factor alpha (TNF-α). The suffix “-imab” in infliximab indicates a chimeric type, differing from the fully human type denoted by “-umab” (e.g., adalimumab). This difference manifests as immunogenicity; the chimeric infliximab is more likely to generate anti-drug antibodies than fully human antibodies 2).
Among biologic agents for non-infectious uveitis, infliximab is the second most frequently used after adalimumab 1). It was first approved in Japan for Behçet’s disease-related refractory uveitis, ahead of other countries.
It is also widely used for systemic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, and Crohn’s disease. Its application in ophthalmology developed as an extension of these uses.
Infliximab (Remicade) is a mouse/human chimeric antibody, with its complementarity-determining regions (CDRs) containing mouse-derived portions. Adalimumab (Humira) is fully human. Chimeric antibodies are more prone to inducing anti-drug antibodies (ADAb) and have a relatively higher risk of infusion reactions 2). On the other hand, infliximab is administered by intravenous infusion, requiring outpatient management, but this also allows for observation of the administration status.
Typical subjective symptoms of diseases for which infliximab is indicated are as follows.
The characteristic ocular findings of the main indications for infliximab are shown below.
| Disease | Main Ocular Findings | Site of Inflammation |
|---|---|---|
| Behçet’s disease | Inflammatory attacks, occlusive vasculitis | Panuveitis |
| Juvenile idiopathic arthritis-associated | Chronic anterior uveitis, band keratopathy | Primarily anterior segment |
| Sarcoidosis | Mutton-fat KP, candle wax exudates | Panuveitis |
| Vogt-Koyanagi-Harada disease | Exudative retinal detachment, sunset glow fundus | Posterior, panuveitis |
Paradoxical inflammation, where new uveitis develops during anti-TNF therapy, has been reported 3). In a case of a rheumatoid arthritis patient who developed bilateral anterior and intermediate uveitis during infliximab treatment, a paradoxical reaction to infliximab was diagnosed after excluding infectious and autoimmune causes 3). This is most commonly reported with etanercept, but can also occur with infliximab 3).
In many cases, it can be treated with steroids while continuing infliximab 3). If uveitis persists or recurs, consider discontinuing the drug or switching to another TNF inhibitor (e.g., adalimumab). In the literature, cases have been reported where switching to adalimumab or changing to tocilizumab resulted in no recurrence 3).
Approved and established efficacy
Behçet’s disease (refractory retinochoroiditis): Approved in Japan in 2007. It is the first-line treatment for cases unresponsive to colchicine or cyclosporine. Reduction in inflammatory attack frequency, improvement in QOL, and improvement in extraocular symptoms have been reported.
Juvenile idiopathic arthritis-associated uveitis: Infliximab and adalimumab are recommended over etanercept. Combination with methotrexate is standard.
Diseases with reported efficacy
Sarcoidosis: Efficacy has been reported in cases resistant to steroids and immunosuppressants.
Vogt-Koyanagi-Harada disease: Efficacy has been reported in refractory cases.
Refractory non-infectious uveitis in general: A cohort study reported that 81.8% achieved clinical remission.
Cystoid macular edema and pars planitis: Effective cases have been reported.
The indication of infliximab for refractory uveitis is considered in the following situations.
Behçet’s disease: When inflammatory attacks are not sufficiently suppressed with continuous administration of colchicine 1 mg/day, or when control is inadequate with cyclosporine (Neoral®) 5 mg/kg/day, administer 5 mg/kg by intravenous infusion every 2 months.
Other non-infectious uveitis: Consider when oral steroids and conventional immunosuppressants (methotrexate, mycophenolate, cyclosporine, etc.) are ineffective or not tolerated 1).
Therapeutic drug monitoring (TDM) includes trough concentration and anti-drug antibody (ADAb) measurement, but currently clinical trials have not shown that TDM significantly improves clinical outcomes 2); therefore, monitoring disease activity remains the mainstay. In an international survey, many specialists perform drug toxicity screening every 6–12 weeks in patients with inactive uveitis 1).
Infliximab is administered by intravenous infusion.
In Japan, it is recommended to administer through an in-line filter with a pore size of 1.2 μm or smaller.
According to the American College of Rheumatology recommendations, infliximab is often used in combination with immunosuppressants such as methotrexate. This may suppress the production of anti-drug antibodies (ADAbs) against the chimeric antibody and allow for lower doses 2). ADAb formation is associated with decreased trough concentrations, increased risk of hypersensitivity reactions, and lower remission rates 2).
In an international survey, 176 of 221 (79.6%) uveitis specialists had experience using infliximab, making it the second most frequently used biologic after adalimumab (98.6%) 1). For Behçet’s disease, azathioprine is the first-line conventional drug (52.0%), and infliximab is used as a biologic by 23.1% of specialists 1).
Biosimilars (follow-on products) such as Inflectra® have reported safety and efficacy in non-infectious uveitis, but further evidence accumulation is needed.
TNF-α (tumor necrosis factor alpha) is a major cytokine in intraocular inflammation, produced by various immune cells such as macrophages, T cells, mast cells, and NK cells. TNF-α induces NF-κB production, cell activation, and apoptosis, and amplifies the production of inflammatory cytokines such as IL-1, interferon-γ, and IL-2 (amplification of the inflammatory cascade).
TNF-α exists in two forms: soluble (circulating) and transmembrane. Infliximab binds with high affinity to both forms, inhibiting their binding to TNF receptors.
Infliximab suppresses intraocular inflammation by neutralizing the pro-inflammatory effects of TNF-α. This pathway is particularly effective against Behçet’s disease (involving CD4+ T cell Th1/Th17 cells) and significantly reduces the frequency of occlusive retinal vasculitis attacks.
TNF-α has both pro-inflammatory and immunomodulatory roles 3). When this balance is disrupted by TNF-α inhibition, a paradoxical effect may occur in some patients, inducing new inflammatory reactions (such as uveitis, scleritis, and optic neuritis) 3). Paradoxical uveitis caused by infliximab often presents as anterior uveitis, and cystoid macular edema has been reported on optical coherence tomography (OCT) 3).
Infliximab, a chimeric antibody, has a higher risk of anti-drug antibody (ADAb) formation compared to fully human adalimumab 2). ADAb formation is associated with decreased trough concentrations, increased risk of hypersensitivity reactions (infusion reactions), and lower remission rates 2). Many assays detect ADAb binding but do not accurately reflect in vivo neutralizing effects, so some patients with positive ADAb may still be in remission 2).
Therapeutic drug monitoring (TDM) including ADAb detection is theoretically attractive, but current randomized trials have not demonstrated that TDM significantly improves clinical outcomes 2). Standardization of ADAb assays and development of methods to assess clinical neutralizing capacity are future research challenges.
A survey by Branford et al. (2025) involving 221 physicians from 53 countries provided important international data on the real-world positioning of infliximab 1), revealing that 23.1% of specialists choose infliximab as a biologic for Behçet’s disease 1).
Biosimilars of infliximab (e.g., Inflectra®) are attracting attention from the perspective of reducing medical costs, and long-term data on safety and efficacy in non-infectious uveitis are expected to accumulate.
