Tocilizumab for the Treatment of Ocular Inflammatory Disease

Abstract

Tocilizumab (TCZ; Actemra®; Roche/Genentech in the US; Chugai Pharmaceutical Co. in Japan) is a recombinant, humanized monoclonal antibody directed against the interleukin-6 (IL-6) receptor and currently approved by the Food and Drug Administration (FDA) and the European Commission to treat adults with moderately to severely active rheumatoid arthritis (RA) and pediatric patients with polyarticular Juvenile Idiopathic Arthritis (JIA) or systemic JIA. The FDA has also approved TCZ to treat giant cell (temporal) arteritis and adults and pediatric patients with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome. In Japan, TCZ is approved for the treatment of Castleman's Disease and Takayasu Arteritis. Sarilumab (Kevzara®; Regeneron in the US; Sanofi outside the US) is a similar fully humanized IL-6 R antagonist indicated for the treatment of adults with moderate to severe rheumatoid arthritis (RA). Common side-effects of IL-6 R inhibition include injection site reaction, upper respiratory symptoms, systemic hypertension, hypercholesterolemia, elevated liver enzymes, neutropenia, and thrombocytopenia. Less common complications include severe, opportunistic infections and intestinal perforation. Siltuximab (Sylvant®; EUSA Pharma) is a chimeric monoclonal antibody targeting IL-6 that is approved in both North America and Europe for the treatment of patients with multicentric Castleman's disease who are both human immunodeficiency virus and human herpesvirus-8 negative. Additional monoclonal antibodies targeting IL-6, including sirukumab (Johnson and Johnson/Centocor), olokizumab (R-Pharm), and clazakizumab (Bristol Myers Squib/ Alder Biopharmaceuticals), are advancing through phase 2/3 clinical development, but have yet to receive regulatory approval in North America or Europe. 1,2 Although not approved specifically for the treatment of ocular inflammatory disease or its complications, a number of studies support the use of TCZ to treat active, noninfectious uveitis or scleritis refractory to conventional immunomodulatory therapies, 3-8 most notably scleritis in the setting of rheumatoid arthritis (RA), 9 JIA-associated uveitis, 9-12 and uveitic macular edema. 13-18 Silpa-archa et al 9 reported on the use of intravenous TCZ, 4 to 8 mg/kg monthly, in a mixed cohort of 17 patients with ocular inflammatory disease refractory to conventional immunotherapy, including five subjects with JIA

Tocilizumab and Abatacept for the Treatment of Childhood Chronic Uveitis: A Monocentric Comparison Experience

“…Moreover, Tocilizumab seems to be a valid option in patients who have failed Abatacept as demonstrated in our cohort of patients and in those of Calvo-Rio et al ( 13 ), containing 3/8 and 6/25 patients previously treated with that drug, respectively. Moreover, in a recent revision of the literature, Cunningham et al ( 27 ) highlighted the potential use of Tocilizumab to treat ocular inflammatory disease refractory to the conventional immunosuppressive therapies, including TNF inhibitors, as second or third-line therapy, not only in adult patients but also in children. However, literature results showed that when Tocilizumab has been administered subcutaneously, it showed a decrease in activity in controlling ocular inflammation and maintaining remission ( 22 , 28 ).…”

Safety and efficacy of 27-gauge transconjunctival vitrectomy for the diagnosis of posterior uveitis or pan uveitis of unknown origin

“…In addition, the levels of IL-10 and IL-6 were investigated in cases suspected of having intraocular lymphoma. In addition, determining IL-6 levels in other cases of uveitis as well enables evaluation of the extent of intraocular inflammation and could thus prove beneficial in selecting treatment options such as tocilizumab [ 31 , 32 ]. Furthermore, the improvement in visual acuity is only a secondary effect.…”

Traitement de la maladie de Vogt-Koyanagi-Harada : Une revue narrative de la littérature

“…Une étude a montré l'efficacité du tocilizumab chez des patients présentant un oedème maculaire cystoïde uvéitique réfractaire aux agents immunosuppresseurs conventionnels ou aux anti-TNF-α (39). Une autre étude a également montré, chez des patients avec uvéites réfractaires sévères, l'efficacité du tocilizumab par voie intraveineuse (40). Le tocilizumab est contre-indiqué chez les patients ayant des antécédents de cancer, de tuberculose, d'infection fongique invasive telle que la candidose, l'aspergillose et la pneumocystose, ou d'infections bactériennes, virales ou parasitaires actives (40).…”

“…Une autre étude a également montré, chez des patients avec uvéites réfractaires sévères, l'efficacité du tocilizumab par voie intraveineuse (40). Le tocilizumab est contre-indiqué chez les patients ayant des antécédents de cancer, de tuberculose, d'infection fongique invasive telle que la candidose, l'aspergillose et la pneumocystose, ou d'infections bactériennes, virales ou parasitaires actives (40). * Certolizumab pégol Le certolizumab pégol est un anticorps monoclonal dirigé contre le TNF-alpha.…”