Treating Still’s disease early with IL-1 inhibition may do more than control inflammation – it could change the disease’s long-term trajectory – according to an international registry study that strengthens growing support for a therapeutic window early in the illness.

Researchers analysed 190 children and adults with Still’s disease treated with canakinumab through the international AutoInflammatory Disease Alliance (AIDA) registry. Patients who started treatment within three months of disease onset were more likely to achieve sustained remission, discontinue treatment and follow a monocyclic disease course than those who began therapy later, despite similar initial response rates.

Key findings

• Patients who started canakinumab within three months of disease onset were almost five times more likely to discontinue treatment because of sustained remission.
• Nearly half (49%) followed a monocyclic disease course compared with 8% of those treated later.
• Early treatment was associated with faster glucocorticoid withdrawal.
• Initial response rates were similar regardless of treatment timing, suggesting the principal benefit of early IL-1 inhibition may lie in altering long-term disease behaviour rather than improving short-term disease control.

Dr Hugh Caterson

Rheumatologist and clinical immunologist, Dr Hugh Caterson of Prince of Wales Hospital, Sydney, said the findings reinforced a growing shift in the way clinicians viewed the disease.

“The important thing is that this shows not only that using a biologic, specifically IL-1, controls the disease effectively, but it gives strong support to the concept that early treatment with these biologics may positively alter the disease course and give patients better long-term outcomes.”

The findings built on last year’s joint recommendations from the European Alliance of Associations for Rheumatology (EULAR) and the Paediatric Rheumatology European Society (PReS), he added, which for the first time recognised adult-onset Still’s disease and systemic juvenile idiopathic arthritis as manifestations of the same disease continuum and recommended biologic therapy targeting either IL-1 or IL-6 as first-line treatment once the diagnosis is established.

Writing in Seminars in Arthritis and Rheumatism [link here], Dr Antonio Vitale of University of Siena, Italy, and colleagues said the data offered further support for the hypothesis that intervening early may influence disease behaviour beyond controlling inflammation.

“Early IL-1 inhibition may be associated with a monocyclic disease pattern rather than a chronic articular or polycyclic course.”

“This finding is consistent with the hypothesis that early targeting of key inflammatory pathways through IL-1 blockade may positively influence long-term disease trajectories.”

Speaking to the limbic, Dr Caterson said the concept of a therapeutic window reflected an evolving understanding of the disease biology.

“There has long been a view that Still’s disease begins with an acute inflammatory phase before evolving into a more chronic form with persistent and sometimes erosive joint disease,” he said.

“The thought is that it starts with autoinflammation, but if that goes untreated for some time, another part of the immune system – mainly the adaptive immune system – starts to activate.

“They haven’t proven it, but this study provides support for the idea that if you treat that autoinflammation promptly, there may be a therapeutic window that prevents that chronic evolution of the disease.”

The study also found patients treated early withdrew glucocorticoids more rapidly, with steroid use falling by 50% within three months compared with 6% among those who started treatment later. By six months, steroid use had fallen by 75% and 32%, respectively.

Dr Caterson said the steroid-sparing effect was another clinically important finding.

“The big outcomes were more disease being monophasic, which I think is huge, and also less steroids being used.”

For Australian clinicians, however, translating those findings into practice remains challenging.

Canakinumab is not PBS-listed for Still’s disease and is prohibitively expensive for routine use. Instead, rheumatologists more commonly rely on anakinra, an IL-1 inhibitor that is typically accessed through hospital compassionate-use arrangements or individual funding applications.

“Anakinra is by far and away what is being used in Australia,” Dr Caterson said.

“But every time it comes up, clinicians are needing to approach hospitals to do individualised patient pathways for treating it.”

He said the accumulating evidence was becoming increasingly difficult to ignore.

“The evidence is getting so strong that we should be thinking about ways to approach the PBAC for some sort of IL-1 inhibition recommendation for Still’s disease.”

The study also highlights another challenge: identifying patients early enough to capitalise on any therapeutic window.

Still’s disease remains a clinical diagnosis, with no definitive diagnostic test. Clinicians must first exclude infection, malignancy and other autoimmune diseases before commencing treatment – a process the investigators acknowledged may delay access to early IL-1 inhibition.

“But we have treatments and we should be actively thinking about it when the question comes up and, where the time is right, starting treatment as soon as we can,” Dr Caterson said.

The authors cautioned that the observational nature of the study meant it could not establish whether earlier treatment itself altered disease course. Patients who presented earlier may have had inherently milder disease, while shorter follow-up among those treated early could also have influenced classification of long-term outcomes.