Arthritis drug found to help debilitating inflammatory disease

The study, results of which were published in the New England Journal of Medicine, was conducted in the Intramural Research Program of the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic cutaneous articular (CINCA) syndrome, is an inflammatory disorder that affects numerous organs and body systems, including the skin, joints, eyes and central nervous system.

Despite treatment to control the inflammation – including high-dose corticosteroids, disease-modifying antirheumatic drugs such as methotrexate, and nonsteroidal anti-inflammatory drugs such as ibuprofen or naproxen – the disease is progressive and often fatal. Up to 20% of children with NOMID don’t survive to adulthood.

While the mechanism of NOMID is not completely understood, research in recent years has revealed mutations in a gene called CIAS1 in approximately 60% of patients with the disease. CIAS1 encodes cryopyrin, which belongs to a group of interacting proteins involved in regulating inflammation and programmed cell death, which plays a crucial role in ridding the body of cells that are no longer needed. The mutations, scientists have found, lead to an imbalance of a cytokine, or chemical messenger, called interleukin-1 (IL-1), which is believed to drive the inflammation that causes damage in patients with the disease.

Isolated case reports have suggested that anakinra might be effective in treating the rash and other symptoms of NOMID. Anakinra is a biologic agent, a medicine based on compounds that are made by living cells and used to stimulate or restore the ability of the immune system to fight disease and/or infection. It works by blocking the effects of IL-1beta, and is approved for treating rheumatoid arthritis.

To determine the possible role of anakinra in treating NOMID, the researchers treated 18 NOMID patients (12 with identifiable CIAS1 mutations) aged four to 32 with daily doses of anakinra based on body weight. At one, three and six months they assessed the treatment’s effectiveness.

All 18 of the patients, they found, had an immediate clinical response to anakinra. Rash and conjunctivitis, both common in NOMID, disappeared within three days. By three months, laboratory measures of inflammation, including erythrocyte sedimentation rate, c-reactive protein and serum amyloid A protein, had improved, and by six months, 33% of the patients showed improved hearing and another half of the patients had no further hearing loss from baseline.

Other confirmed benefits of treatment included disappearance or lessening of headaches, reduction of central nervous system lesions, ability to lower corticosteroid doses, and remission of inflammation in more than half of patients by month six. At month three, disease flared in 11 patients when they were withdrawn from anakinra as part of the study, but when anakinra was restarted, the disease quickly responded again.

Furthermore, anakinra was safe in this clinical investigation. Unlike some other treatments used for NOMID, it caused no serious side effects in any of the patients during the study.

The researchers pointed out that daily injections would be required for any long-term treatment.

“NOMID is a devastating disease for which previously there was little understanding or effective treatment,” says NIAMS director Dr Stephen Katz. “This study not only provides hope – in the way of an already-available agent – but it also provides a better understanding of the mechanism of the disease’s damaging effects.”