Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous ( IV ) doses to patients with active, chronic, noninfectious uveitis.
A multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial compared the efficacy and safety of different IV and subcutaneous ( SC ) doses of Secukinumab in patients with noninfectious uveitis.
Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy.
Patients were randomized to Secukinumab 300 mg subcutaneous every 2 weeks for 4 doses, Secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or Secukinumab 30 mg/kg IV every 4 weeks for 2 doses.
Intravenous or subcutaneous saline was administered to maintain masking.
Efficacy was assessed on day 57 ( 2-4 weeks after last dose ).
Percentage of patients with treatment response was defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening.
Percentage of patients with remission was defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening.
Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg subcutaneous dose, produced higher responder rates ( 72.7% and 61.5% vs. 33.3%, respectively ) and remission rates ( 27.3% and 38.5% vs. 16.7%, respectively ).
Statistical and clinical superiority for the 30 mg/kg intravenous dose compared with the 300 mg subcutaneous dose was established in a Bayesian probability model.
Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring intravenous dosing.
Secukinumab, administered in intravenous or subcutaneous formulations, appeared safe and was well tolerated.
In conclusion, intravenous Secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy.
Greater activity with intravenous dosing suggests that patients may not receive sufficient drug with subcutaneous administration.
High-dose intravenous Secukinumab may be necessary to deliver Secukinumab in therapeutic concentrations. ( Xagena )
Letko E et al, Ophthalmology 2015; Epub ahead of print