A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease

Abstract

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 150 mg (or 2 mg/kg in patients ≤40 kg) or 300 mg (or 4 mg/kg) with escalation up to 600 mg (or 8 mg/kg) every 4 weeks. Full remission was remission of patientreported 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 Staphylococcus aureus infection) occurred. Conclusions 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. ClinicalTrials.gov identifier NCT00770601.

Administration of the Interleukin-1 Inhibitor Canakinumab in Children with Autoinflammatory Diseases and Systemic Juvenile Arthritis: the Report for Case Series

“…В работе C. H. Sibley и соавт. 6 пациентов с CINCA/NOMID были переключены с ана-кинры на канакинумаб согласно протоколу исследования [26]. Необходимо отметить, что состояние всех больных обострилось на фоне отмены анакинры, что свидетель-ствует о необходимости непрерывного лечения таких больных.…”

Investigational new drugs for the treatment of acute coronary syndrome

“…This has resulted in a significant 'drop out' of investigational drugs after larger populationbased studies have been conducted on the drugs (e.g., Phase III trials involving darapladib and varespladib) [76][77][78][79]. There have been a number of successful preliminary studies involving investigational drugs to modify myocardial injury (e.g., canakinumab and cyclosporin [85,99]); however, further investigation is pending [86].…”

“…Canakinumab is a monoclonal antibody directed against interleukin 1-b, and has been approved for use in rare inflammatory disorders [85]. The CANTOS trial [86] will test whether reducing inflammation with canakinumab in patients with a history of ACS can reduce the risk of recurrent cardiovascular events up to 24 months.…”

Immunotherapeutic Biologic Agents to Treat Autoinflammatory Diseases

“…It also acts as a soluble decoy for IL-1α, also preventing this cytokine from binding with the receptor. These agents control FCAS and MWS and are partly beneficial in NOMID [32][33][34][35][36][37].…”