NIAMS Scientists: RA Drug Halts Organ Damage in Inflammatory Genetic Disorder

BIO publishes quarterly newsletters for its members which focus on the therapeutic areas of member companies. The newsletters include updates from biotech stakeholders around Washington, including Congress, FDA, NIH, and patient organizations. The following is an excerpt from the "Focus on Rheumatology/Inflammation/Anesthesia/Pain" newsletter. To find funding opportunities and learn about what Congress and the federal agencies are doing for biotechnology, please click here to read the “Focus on Rheumatology/Inflammation/Anesthesia/Pain" newsletter.

A new study shows that Kineret (anakinra), a medication approved for the treatment of rheumatoid arthritis, is effective in stopping the progression of organ damage in people with neonatal-onset multisystem inflammatory disease (NOMID). This rare, debilitating genetic disorder causes persistent inflammation and ongoing tissue damage. The research was performed by scientists at NIAMS.

Kineret, one of a relatively new class of biologics, blocks the activity of interleukin-1 (IL-1), a protein made by cells of the immune system. IL-1 is overproduced in NOMID, leading to damaging inflammation. Previous work by the same NIAMS group showed that blocking IL-1 was effective in relieving symptoms of NOMID. However, this is the first study to show that Kineret works over the long-term and, at higher doses, can also control damage that often results in vision and hearing loss, and brain lesions.

“Inflammation prolonged over many years will eventually cause irreversible damage and loss of function,” said lead author Dr. Raphaela Goldbach-Mansky. “We knew we could effectively block inflammation in the inner ear and in the brain and eyes. The next step was to find out if we could sufficiently prevent the progression of hearing or vision loss.”

Study participants, who ranged in age from 10 months to 42 years, were treated with daily doses of Kineret based on body weight for at least 36 months and as long as 60 months. Disease activity was monitored with blood tests to measure C-reactive protein, and by daily diaries kept by the patients. The researchers also used sensitive MRI imaging methods to assess inflammation in the inner ear and brain.

Researchers found the initial Kineret doses used were insufficient to control organ inflammation, but by increasing the dose, they were able to do so. By preventing organ inflammation, scientists were able to preserve organ function in most patients. In addition, the scientists found ways to predict who is at greatest risk of hearing and vision loss.

“The few patients in the study who had hearing loss were also the ones who continued to have inflammation in the inner ear,” said the study's first author Dr. Cailin H. Sibley. “We also found that people who had thin optic nerves when we assessed their vision were more likely to lose vision than those who had thick optic nerves, simply because they had already lost fibers due to untreated disease and, therefore, started with a huge disadvantage.”

These findings point to the importance of early diagnosis and treatment to keep organ damage from developing. “We are continuing the study with an emphasis on enrolling very young children to prospectively show that we can prevent any organ damage from developing if we start treatment early in life,” Goldbach-Mansky said.

Because IL-1 is needed to fight infections, there has been concern that blocking it with high doses of Kineret might leave the body vulnerable to infections. But overall, the study drug was well tolerated.

For more information on this research, click here.

For more information, please click here to read the “Focus on Focus on Rheumatology/Inflammation/Anesthesia/Pain” newsletter.