Abstract
Purpose:
The cryopyrin-associated periodic syndromes (CAPS) are a group of rare autosomal dominant autoinflammatory disorders associated with mutations in the NLRP3 gene leading to excessive interleukin-1 release. CAPS encompasses three different entities: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological cutaneous and articular syndrome (CINCA/NOMID). Symptoms include rash, arthralgia, arthritis, fever, inflammation of the eyes and hearing loss. We take care for a 5-generation-family with MWS with various symptoms, due to the NLRP3 mutation A439V. Here we report about the response to canakinumab (Ilaris, human monoclonal antibody targeted IL-1-beta).
Methods:
A retrospective observational study on 13 family members was performed. NLRP3 gene mutations were determined. All patients had standardized clinical and ophthalmologic assessments. The most common organ manifestations such as rash, arthritis, hypacusis, and uveitis/conjunctivitis were compared before and during therapy with canakinumab (300mg every 8-10 weeks in 10 patients, 150mg every 8 weeks in 2 patients, and 150mg every 2 months in 1 patient).
Results:
13 (7 female and 6 male) symptomatic family members were enrolled in the study. Eleven (85%) of the 13 symptomatic family members carried the A439V mutation. Two (15%) patients and were heterozygous carriers of Alanin 439 (GCG)-Valin (GTG)-/p.Ala439Val-/A4339V substitution. Before treatment with canakinumab, the most common organ manifestations were arthritis (77%), rash (100%), conjunctivitis (69%), anterior uveitis (69%), and hypacusis (31%). During therapy with canakinumab, neither anterior uveitis nor rash were observed. Moderate conjunctivitis and minimal arthritis were seen in one patient only.
Conclusions:
Therapy with canakinumab seems to be effective in mutation-positive family members with MWS.
Keywords: 746 uveitis-clinical/animal model •
462 clinical (human) or epidemiologic studies: outcomes/complications •
557 inflammation