Efficacy and safety of intravenous secukinumab in noninfectious XXXX requiring steroid-sparing immunosuppressive therapy.

@entity1 @entity5863 @entity1596 @entity228 @entity4155
PURPOSE: Secukinumab, a fully human anti- @entity4155 monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to @entity1 with active, chronic, noninfectious @entity1596 . This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in @entity1 with noninfectious @entity1596 . DESIGN: Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. @entity1 : Thirty-seven @entity1 with active noninfectious intermediate @entity1596 , posterior @entity1596 , or @entity5863 who required corticosteroid-sparing immunosuppressive therapy. METHODS: @entity1 were randomized to secukinumab 300 mg SC 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 SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). MAIN OUTCOME MEASURES: Percentage of @entity1 with treatment response, 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 @entity228 dose and without @entity1596 worsening or (2) reduction in corticosteroid dosages to prespecified levels without @entity1596 worsening. Percentage of @entity1 with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or @entity1596 worsening. RESULTS: Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC 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 IV dose compared with the 300 mg SC 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 IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated. CONCLUSIONS: Intravenous secukinumab was effective and well tolerated in noninfectious @entity1596 requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that @entity1 may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations.
