Development and effect of antibodies to anakinra during treatment of severe CAPS: sub-analysis of a long-term safety and efficacy study.

Anakinra is an effective, well-tolerated, long-term anti-inflammatory treatment for cryopyrin-associated periodic syndromes (CAPS), yet evidence shows that it can induce the development of anti-drug antibodies (ADA). This analysis aims to determine ADA occurrence in CAPS patients and elucidate their effects on anakinra dosing and drug efficacy. A post hoc analysis was performed on data from a long-term safety and efficacy study in patients with severe CAPS. Patients were initiated on an anakinra dose of 1.0-2.4 mg/kg once daily subcutaneously, which was increased (in 0.5-1.0 mg/kg increments) to 2.0-5.0 mg/kg/day according to clinical need (median 3.1 mg/kg/day). ADA, serum amyloid A (SAA), and C-reactive protein (CRP) levels were measured at various time points, and pharmacokinetic (PK) parameters at 1 and 3 months. Efficacy was evaluated using a diary symptom sum score (DSSS), and SAA and CRP levels were evaluated as proxies of efficacy. Safety was evaluated by an analysis of adverse events (AEs). Anakinra dose levels were unrelated to ADA status. A high proportion of patients with at least one post-baseline assessment developed ADA (83%), the majority (79%) within 3 months. However, anakinra treatment markedly improved symptoms and was effective regardless of the presence of ADA; the annual rates of AEs were comparable between ADA-negative and ADA-positive patients. While ADA are likely to occur in CAPS patients treated with anakinra, our evidence shows that chronic daily subcutaneous treatment with anakinra is safe and effective regardless of the development and presence of ADA.