Open-Label, Phase II Study to Assess the Efficacy and Safety of Canakinumab Treatment in Active Hyperimmunoglobulinemia D With Periodic Fever Syndrome

Objective. To evaluate the efficacy and safety of canakinumab treatment in active hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). Methods. This was a 3-part, open-label study with a 6-month treatment period (P1; 300 mg or 4 mg/kg q6w), a 6-month withdrawal period (P2), and a 24-month treatment period (P3). The primary endpoint was reduction in frequency of attacks during treatment period compared with the historical period (HP; period in which patients did not receive drugs other than NSAIDs and/or steroids). Results. All nine patients completed P1 and P2, whereas only eight completed P3. All patients achieved a complete response during P1, and only two required dose adjustments. The median number of attacks per patient decreased from 5 (3–12) during HP to 0 (0–2) during P1. During P2, seven out of nine patients flared with a median of 110 days (62-196) after the last canakinumab dose. Laboratory parameters were normalized at Day 15 and remained at normal levels throughout the study. The blood transcriptome assessed during P1 showed upregulated interferon and myeloid-related inflammatory responses in untreated patients compared to healthy controls, which rapidly decreased following canakinumab injection, reaching levels comparable to those of healthy controls. At least one adverse event (AE) was detected in all nine patients; most of them being mild in intensity, with infections being the most frequent AE. Serious AEs were reported in four patients. Conclusions. This study demonstrated the efficacy and safety of canakinumab treatment to control active HIDS and to suppress inflammatory transcriptional responses. This article is protected by copyright. All rights reserved.