Dr. Goldbach-Mansky has received grant support from Regeneron, Novartis, and Swedish Orphan Biovitrum AB.
Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: A cohort study to determine three- and five-year outcomes†
Article first published online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2375–2386, July 2012
How to Cite
Sibley, C. H., Plass, N., Snow, J., Wiggs, E. A., Brewer, C. C., King, K. A., Zalewski, C., Kim, H. J., Bishop, R., Hill, S., Paul, S. M., Kicker, P., Phillips, Z., Dolan, J. G., Widemann, B., Jayaprakash, N., Pucino, F., Stone, D. L., Chapelle, D., Snyder, C., Butman, J. A., Wesley, R. and Goldbach-Mansky, R. (2012), Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: A cohort study to determine three- and five-year outcomes. Arthritis & Rheumatism, 64: 2375–2386. doi: 10.1002/art.34409
ClinicalTrials.gov identifier: NCT00069329.
- Issue published online: 26 JUN 2012
- Article first published online: 26 JUN 2012
- Accepted manuscript online: 31 JAN 2012 10:37AM EST
- Manuscript Accepted: 24 JAN 2012
- Manuscript Received: 26 OCT 2011
- Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Intramural Research Programs of the National Cancer Institute
- National Institute on Deafness and Other Communication Disorders
- National Eye Institute
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- NIH Clinical Center
Blocking interleukin-1 with anakinra in patients with the autoinflammatory syndrome neonatal-onset multisystem inflammatory disease (NOMID) reduces systemic and organ-specific inflammation. However, the impact of long-term treatment has not been established. This study was undertaken to evaluate the long-term effect of anakinra on clinical and laboratory outcomes and safety in patients with NOMID.
We conducted a cohort study of 26 NOMID patients ages 0.80–42.17 years who were followed up at the NIH and treated with anakinra 1–5 mg/kg/day for at least 36 months. Disease activity was assessed using daily diaries, questionnaires, and C-reactive protein level. Central nervous system (CNS) inflammation, hearing, vision, and safety were evaluated.
Sustained improvements in diary scores, parent's/patient's and physician's global scores of disease activity, parent's/patient's pain scores, and inflammatory markers were observed (all P < 0.001 at 36 and 60 months). At 36 and 60 months, CNS inflammation was suppressed, with decreased cerebrospinal fluid white blood cell counts (P = 0.0026 and P = 0.0076, respectively), albumin levels, and opening pressures (P = 0.0012 and P < 0.001, respectively). Most patients showed stable or improved hearing. Cochlear enhancement on magnetic resonance imaging correlated with continued hearing loss. Visual acuity and peripheral vision were stable. Low optic nerve size correlated with poor visual field. Bony lesions progressed. Adverse events other than viral infections were rare, and all patients continued to receive the medication.
These findings indicate that anakinra provides sustained efficacy in the treatment of NOMID for up to 5 years, with the requirement of dose escalation. Damage progression in the CNS, ear, and eye, but not bone, is preventable. Anakinra is well tolerated overall.