Treatment with the IL-17 blocking antibody secukinumab (AIN457) does not interfere with the efficacy of Influenza and Meningococcal vaccination in healthy subjects. Results of an open-label, parallel group, randomized, single-center study

Objectives: to evaluate the efficacy of influenza and meningococcal vaccinations in healthy subjects exposed to the anti-IL-1 mAb secukinumab. Methods: open-label, parallel groups, randomized single-center study in 50 healthy subjects. Subjects received a single secukinumab (AIN457) 150 mg s.c. dose or no treatment, followed by influenza and meningococcal vaccinations two weeks later. Primary efficacy variables: responses to vaccinations as ≥4-fold increase in Ab titer in ≥2/3 serotypes (influenza) and ≥4-fold increase (meningococcus), both at 4 weeks post-vaccination. Immunogenicity was assesed as hemagglutination inhibition (HI, influenza) and Serum Bactericidal Assay (SBA, Neisseria meningitidis). Results: all 50 subjects, randomized to secukinumab (n=25) or control (n=25) completed the study. Antibody responses to vaccinations measured at four weeks post-vaccination were comparable in both groups, with responses following influenza vaccine of 20/25(80%) for both groups and following MenC vaccine of 19/25(76%) for secukinumab and 18/25(72%) for control. The differences between groups were 0% (90% CI -19%,19%) and 4% (90% CI -16%,24%) for influenza and MenC vaccines respectively. Antibody responses were also comparable in the two groups at different time-points assessed. Headache was the most frequently reported adverse event. No deaths or serious adverse events were reported during the study. Conclusions: Blockade of IL-17 by secukinumab (AIN457) does not appear to interfere with the efficacy of influenza and meningococcal vaccinations, as assessed by the achievement of antibody protective levels. A protective (≥4 fold) immune response to both vaccinations at 4 weeks was achieved in 80 and 76% of subjects exposed to secukinumab and control, respectively

A 24 Month Open Label Study of Canakinumab in Neonatal-Onset Multisystem Inflammatory Disease

Objective: To study efficacy and safety of escalating doses of canakinumab, a fully human anti-IL-1β monoclonal antibody in the severe cryopyrin associated periodic syndrome, neonatal-onset multisystem inflammatory disease (NOMID). Methods: 6 patients were enrolled in this 24-month, open label phase I/II study. All underwent anakinra withdrawal. The initial subcutaneous canakinumab dose was 150mg (or 2mg/kg in patients ≤40kg) or 300mg (or 4mg/kg) with escalation up to 600mg (or 8mg/kg) every 4 weeks. Full remission was remission of patient-reported clinical components and measures of systemic inflammation and CNS inflammation. Hearing, vision and safety were assessed. Primary endpoint was full remission at Month 6 Results: All patients flared after anakinra withdrawal, and symptoms and serum inflammatory markers improved with canakinumab. All patients required dose escalation to the maximum dose. At Month 6, none had full remission, although 4/6 achieved inflammatory remission, based on disease activity diary scores and normal C-reactive proteins. None had CNS remission; 5/6 due to persistent CNS leucocytosis. At the last study visit, 5/6 patients achieved inflammatory remission and 4/6 had continued CNS leucocytosis. Visual acuity and field were stable in all patients, progressive hearing loss occurred in 1/10 ears. Adverse events (AEs) were rare. One serious AE (abscess due to a methicillin-resistant Staph. aureus infection) occurred. Conclusion: Canakinumab at the studied doses improves symptoms and serum inflammatory features of NOMID, although, low grade CNS leukocytosis in four patients and headaches in one additional patient persisted. Whether further dose intensifications are beneficial in these cases remains to be assessed

A Phase II Study to Evaluate Dosing and Preliminary Safety and Efficacy of Canakinumab in Systemic Juvenile Idiopathic Arthritis With Active Systemic Features

Objectives: To assess dosing, preliminary safety, and efficacy of canakinumab, a fully human anti-interleukin-1β (IL-1β) antibody, in children with systemic juvenile idiopathic arthritis (sJIA) and active systemic features. Methods: In this open-label, dose-escalation, phase II study, children with sJIA who were ≥ 4 years of age, with fever, and receiving ≤ 0.4 mg/kg/d of corticosteroids, were administered a single subcutaneous (sc) dose of canakinumab, 0.5–9 mg/kg and were re-dosed upon relapse. Response was assessed according to adapted American College of Rheumatology (ACR) pediatric criteria. Results: 23 Children (aged 4–19 years) with active disease were enrolled; 1 patient was excluded and 3 re-enrolled patients were included twice in the efficacy analysis. By day 15 of the first treatment cycle, 15/25 (60%) of patients achieved an adapted ACR ped 50 with 4 of them achieving inactive disease status. Response was sustained over time with 11/13 patients able to maintain response throughout the study. 8/11 Responders receiving steroids at baseline decreased their steroid dose from 0.38 to 0.13mg/kg/day over the first 5 months, with 4 patients able to discontinue. At a dose of canakinumab 4 mg/kg sc every 4 weeks, the median percentage of patients predicted to relapse within 4 weeks was estimated to be 6% (95% confidence interval, 1% to 21%). Therapy was generally well tolerated and few patients experienced injection-site reactions. Conclusions: Canakinumab has a promising preliminary safety and efficacy profile in this limited cohort. This trial warrants further studies in a larger population of children with sJIA