Background/Purpose: Hyper-IgD with periodic fever syndrome (HIDS) is a recessively inherited autoinflammatory disease due to biallelic MVK mutations. It is characterized by 4-6 days-long acute inflammatory episodes, which typically start during infancy and recur every 4-6 weeks. Previous studies suggested IL-1 blockade as a potential therapy. However, little information is available about the efficacy and safety of the fully human anti-IL-1b monoclonal antibody canakinumab (CAN) in active HIDS.

Methods: The present study is a multicenter, open-label, and single treatment arm study with a 6-month treatment period (TP) with CAN and a max. 6-month follow-up period (FP). Inclusion criteria were age ≥2 yr. old, biallelic MVK mutations, and active disease defined by ≥3 acute flares in the 6-month historical period (HP, period in which patients did not receive drugs other than symptomatic treatment with NSAIDs and/or steroids) and C-reactive protein (CRP)>10 mg/L. The CAN dose in the TP was 4 mg/kg (max. 300mg) Q6-wks, with a dose up-titration to 6mg/kg (max. 450mg) if a flare occurred during the first 6-weeks. The primary objective was to assess the efficacy of CAN to reduce the flare rate during the TP compared with the HP. Secondary objectives included evaluation of changes in key disease features, disease control during TP, time to flare after the last CAN dose and safety.

Results:

Nine patients (6 F, 3 M) from 3 centers were included. Median age was 17.3 yr (5-29 yr) and median disease duration since diagnosis was 4.1 yr (1-25 yr). The median of number of flares/patient with CAN reduced from 5 (3-12) during HP to 0 (0-2). During FP 7/9 patients flared, with a median of 110 days (62-196 days) after the last CAN dose. At baseline, physicians rated 6 and 3 patients as having no or poor disease control, respectively. At day 4 of TP, all patients were rated as having good/excellent disease control. At baseline, 8/9 patients had moderate/severe fever, 8/9 had mild/moderate lymphadenopathy, 5/9 had mild/moderate abdominal pain and 4/9 had mild/moderate apthous ulcers. From day 4 of TP onwards, no patient referred fever or abdominal pain, and only one patient had mild to moderate lymphadenopathy and apthous ulcers. At baseline, the median plasma levels of CRP and serum amyloid A (SAA) were elevated (CRP: 117.7 mg/L and SAA: 688.5 mg/L; normal values ≤10 mg/L in both cases). At day 15 of TP both plasma levels normalized (CRP: 0.8 mg/L; SAA: 2.6 mg/L) and were maintained. At least one adverse event (AE) was detected in 8 patients, most of them being of mild (76%) or moderate (18%) severity. Respiratory tract infections were the most common AE detected. Two patients reported a serious AE, one patient with an acute inflammatory flare leading to hospitalization, and another one had a gastrointestinal bleed and peritonitis separately (this patient was on peritoneal dialysis from amyloidosis induced by renal failure). No AEs led to CAN discontinuation.

Conclusion: CAN in active HIDS markedly reduced the rate of acute flares, and a sustained good/excellent disease control was observed. Most AEs registered were mild/moderate and all of them were manageable. Further studies are needed to better define CAN treatment in active HIDS.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/canakinumab-treatment-in-active-hyper-igd-with-periodic-fever-syndrome/