Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome.
OBJECTIVE
Cryopyrin-associated periodic syndromes (CAPS) are a group of rare autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA syndrome) is the most severe phenotype, with fever, rash, articular manifestations, and neurologic and neurosensory involvement. CAPS are caused by mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been shown to be an effective treatment; however, data on long-term efficacy and safety have been sparse. This study was undertaken to assess the long-term efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome.


METHODS
We retrospectively analyzed the medical records of NOMID/CINCA syndrome patients referred to 2 centers, who had started anakinra treatment before June 2007.


RESULTS
There were 10 patients with NOMID/CINCA syndrome who had been treated with anakinra. The patients' ages at the time anakinra treatment was initiated ranged from 3 months to 20 years. They had been followed up for 26-42 months. Sustained efficacy in the treatment of systemic inflammation and, in some cases, neurologic involvement and growth parameters, was achieved. The dosage of anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous system inflammation and deafness persisted in some patients, especially if there had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in cases in which it was present at treatment initiation, but no new lesions developed. No effect on overgrowth arthropathy was observed. Adverse events consisted of mild injection-site reactions.


CONCLUSIONS
The present results indicate that anakinra treatment is effective over the long term in NOMID/CINCA syndrome. However, treatment has to be initiated before irreversible lesions develop, and, particularly in very young patients, dosage adjustment is required.
Neven
Bénédicte
B
Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, INSERM U768, Université René Descartes-Paris 5, Paris, France. benedicte.neven@nck.aphp.fr
Marvillet
Isabelle
I
Terrada
Celine
C
Ferster
Alice
A
Boddaert
Nathalie
N
Couloignier
Vincent
V
Pinto
Graziella
G
Pagnier
Anne
A
Bodemer
Christine
C
Bodaghi
Bahram
B
Tardieu
Marc
M
Prieur
Anne Marie
AM
Quartier
Pierre
P
D000293:Adolescent; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D003638:Deafness / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004660:Encephalitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D012189:Retrospective Studies; D013577:Syndrome; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein