IL-1 blockade improves long-term outcome of NOMID patients
MedWire News: Anakinra, a drug approved for the treatment of rheumatoid arthritis, stops the progression of organ damage for at least 5 years in patients with neonatal-onset multisystem inflammatory disease (NOMID), US researchers report.
NOMID is the most severe clinical phenotype of a spectrum of autoinflammatory disorders, termed cryopyrin-associated periodic syndromes, explain Raphaela Goldbach-Mansky (National Institutes of Health, Bethesda, Maryland) and colleagues.
It is characterized by systemic and organ-specific inflammation that can lead to progressive hearing and vision loss, cognitive impairment, physical disability, infections, and a mortality rate of up to 20% before adulthood.
Blocking interleukin (IL)-1 with drugs such as anakinra, reduces inflammation in patients with NOMID, but the impact of long-term treatment is unknown.
To investigate, Goldbach-Mansky and team treated 26 NOMID patients, aged 10 months to 42 years, with anakinra 1-5 mg/kg per day for at least 36 months.
Disease activity was monitored by C-reactive protein (CRP) levels and by daily diaries and health-assessment questionnaires kept by the patients or their parents. The researchers also used magnetic resonance imaging (MRI) to assess inflammation in the inner ear and brain.
They report in Arthritis and Rheumatism that all patients achieved and sustained a clinical and laboratory response to anakinra. Scores for daily diaries and pain (measured on a visual analog scale) significantly decreased from baseline to 36 months, and then remained stable between 36 and 60 months.
Furthermore, all patients achieved laboratory remission (defined as a CRP level ≤0.5 mg/dL) at some point during the study; at 12 months, 46% of patients were in laboratory remission compared with 50% at 24 months, 58% at 36 months, and 65% at 60 months. But, the researchers note that remission and relapse was a common occurrence associated with infection or stress.
In terms of organ-specific outcomes, central nercous system inflammation was suppressed at both 36 and 60 months, with significantly decreased cerebrospinal fluid, white blood cell counts, albumin levels, and opening pressures, compared with baseline.
Hearing improved or remained stable in 80% of ears tested. Patients with worsening hearing loss had significantly higher mean CRP levels over the first 36 months of the study compared with those with stable or improved hearing.
In addition, the researchers observed that higher cochlear enhancement scores on MRI were associated with continued hearing loss.
Eye examination showed that visual acuity and peripheral vision were stable in 88% of patients at 60 months. All three patients with worsening vision had severely atrophic optic nerves at baseline, Goldbach-Mansky et al note.
Furthermore, peripheral vision decreased with decreasing optic nerve thickness, indicating that "optic nerve thickness measurements before anakinra treatment may thus identify patients at risk of vision loss, and may be useful in monitoring the optic nerve on treatment."
Bone was the only part of the body that did not respond to treatment, despite dose escalation. Indeed, the volume of bony lesions increased significantly over the course of the study.
The researchers observed few adverse events other than viral infections and all patients remained on medication throughout the study.
Goldbach-Mansky said in a press statement that 5 years of treatment with anakinra "is safe and effective, and can prevent organ damage" in patients with NOMID.
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By Laura Cowen