In a study published in Annals of the Rheumatic Diseases, an international team has successfully tested a molecule inhibitor of interleukin-18, a protein involved in immune response. These encouraging results in terms of safety and efficacy are paving the way for a new kind of treatment, not only for Still's disease, but other rare inflammatory diseases, too.

Still's disease is a serious orphan disease manifested by high fevers, skin and joint involvement, including paralysis, as well as damage to other organs such as the liver or spleen. It is caused by a deregulation of the immune system triggering an acute inflammatory response.

In its adult form, Still's disease affects about 1 in 100,000 people each year, with its infantile form being ten times more common. This rare condition attacks on several organs that may threaten the quality of life – or even life – of those affected. While the cause is still unknown, genetic factors have been identified in other, similar syndromes.

Cem Gabay, a professor at UNIGE's Faculty of Medicine and Head of the Geneva University Hospitals (HUG) Rheumatology Department, is one of the world's leading specialists in these complex diseases and part of a European consortium whose aim is to better understand the causes and pathology of these inflammatory conditions.

Interleukin-18 (IL-18) is a proinflammatory cytokine, which specializes in immune and inflammatory responses. "Recently, we successfully demonstrated the key role of IL-18 in Still's disease", says Professor Gabay. "Our idea was therefore to block the harmful action. It is also worth pointing out that the treatments currently offered to patients are very empirical, so our goal was to finally give them a safe and approved treatment."

While IL-18 is useful for protecting the body against external pathogens, too much of this protein leads to a harmful overactivation of the immune system, resulting in the various symptoms presented in patients. There is a naturally occurring inhibitor ("IL-18 binding protein"), whose function is to bind to IL-18 to form an inactive complex, but people with Still's disease produce more IL-18 than its inhibitor, which triggers their symptoms.

The main objective of this study was to verify the safety of the IL-18 inhibitor and to confirm its efficacy on the clinical manifestations of the disease. Twenty-three patients, mostly suffering from forms of the condition that are particularly refractory to the usual treatments, were enrolled and divided into two groups: one receiving 80 mg, and the other 160 mg, via three subcutaneous injections per week for 12 weeks.

Professor Gabay summarises the results, "We were initially reassured by the safety profile: there were very few serious side effects, only one of which was possibly related to the drug itself. In addition, 50% of patients in both treatment groups showed a positive response to the drug after three weeks of treatment, and their symptoms decreased over the entire 12 weeks of follow-up."

"In contrast, patients who didn't have a positive 80 mg response did not have one with 160 mg either. These first results are extremely encouraging and mean we can plan a phase 3 trial to better evaluate the effectiveness of the drug." Researchers are currently in phase 2, which aims to ensure the safety of the product and to determine the optimal dose.