Blockade of Tumor Necrosis Factor-Alpha: A Role for Adalimumab in Neovascular Age-Related Macular Degeneration Refractory to Anti-Angiogenesis Therapy

Abstract

Aims: To report a case of wet age-related macular degeneration (wet-AMD) refractory to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in a patient who showed visual and anatomical improvement and stabilization after starting a subcutaneous treatment course with adalimumab, an anti-tumor necrosis factor-alpha (TNF-α) drug, for concomitant Crohn's disease. Methods: Observational case report of a female patient. Ophthalmological evaluation was performed by slit lamp and ophthalmoscopy (posterior pole and anterior segment). Best-corrected visual acuity (BCVA) was determined, and imaging was performed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Intravitreal therapies used and treatment with anti-TNF-α were recorded. Results: A 64-year-old woman with wet-AMD was treated with fourteen intravitreal injections of ranibizumab (0.5 mg) for a period of 40 months with intervals of 1-6 months. She initially showed a good visual and anatomical response to periodic anti-VEGF treatment but during check visits, anatomical and functional responses deteriorated. At the 40-month follow-up, the patient had developed Crohn's disease, and her rheumatologist started treatment with adalimumab (40 mg subcutaneously every 2 weeks). During the 25 months of treatment with adalimumab, the patient did not require any additional intravitreal anti-VEGF treatments because her BCVA, clinical, and OCT findings improved and remained stable. Conclusions: We described a case of a patient with wet-AMD refractory to anti-VEGF therapy, which clinically benefited from subcutaneous adalimumab therapy. Treatment with subcutaneous anti-TNF-α in combination with anti-VEGF therapy avoids the high cost and risks related to multiple intravitreal anti-VEGF injections with good functional and anatomic outcomes.

Involvement of Innate Immune System in Late Stages of Inherited Photoreceptor Degeneration

“…It is well established that the TNF pathway is a key mediator of inflammation in many ocular diseases including diabetic retinopathy, uveitis, proliferative vitreoretinopathy, macular edema and wet AMD 17 , 66 . We previously showed that in the early stages of rcd1 and xlpra2 disease, TNF-superfamily members are upregulated and may thus contribute to the disease pathogenicity 10 .…”

Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα

“…In addition to being an inducer of the NF‐κB pathway, TNFα presents increased expression with human ageing and in age‐related degenerative diseases such as Alzheimer's disease . Importantly in relation to the RPE, TNFα was shown to increase the production and secretion of the angiogenic VEGF protein, a known contributor to development of wet (neovascular) AMD, and anti‐TNFα injections helped improve vision of wet AMD patients …”

Increased Nonexudative Age-Related Macular Degeneration Diagnosis Among Medicare Beneficiaries With Rheumatoid Arthritis

“…TNF-α acts as a proinflammatory cytokine that is produced by macrophages and T cells 23. As a powerful proinflammatory cytokine, TNF-α has been targeted in RA24–28 as well as neovascular AMD therapies,29 and recent findings have supported interactions between TNF-α and the complement system 30,31. Biologics targeting TNF-α, such as infliximab, adalimumab, and etanercept, are currently approved treatments for RA by the US Food and Drug Administration.…”