AMSTERDAM – Rather than waiting for other drugs or immunotherapies to fail, an immediate up-front but time-limited course of an interleukin-1 receptor (IL-1R) antagonist induced rapid and sustained remissions in most children with systemic juvenile idiopathic arthritis (JIA), according to 5-year data presented at the European Congress of Rheumatology.
In the latest follow-up of a protocol first described in 2014, over 90% of patients still had inactive disease, 75% of whom were completely off therapy, reported, of the division of pediatrics at University Medical Center, Utrecht, the Netherlands.
“Translating this into clinical practice, you could say that there might be a window of opportunity early in systemic JIA in which the innate immune system is the major player and perhaps you could down-regulate this to control the inflammation,” Dr. Vastert explained.
Citing a series of experimental studies at his institution that suggest immune mediators change as systemic JIA evolves from an acute to a chronic phase, Dr. Vastert believes that early use of an anti–IL-1R therapy may alter the trajectory of systemic JIA, compared with when it goes untreated or is treated with conventional therapies.
In the original series reported in 2014 (), data were presented on 20 patients. All fulfilled the International League of Associations for Rheumatology criteria for systemic JIA. They were treated with anakinra after failing to respond to indomethacin but before receiving any other therapy, including corticosteroids, disease-modifying antirheumatic drugs, or other biologics.
In the protocol described in the initial publication, a stop-therapy strategy permitted treatment discontinuation after 3 months in those who met American College of Rheumatology criteria for 90% improvement (ACR Pedi 90) in JIA.
By 1 year, 73% of the patients had met criteria to stop therapy. Of 11 patients followed for 3 years, 10 met criteria for disease remission, 8 of whom were off medication. The remaining two continued to receive anti–IL-1R or another therapy.
The systemic JIA cohort at Dr. Vastert’s institution has now grown to 50 patients, of whom 42 patients have received first-line anakinra. Among the 25 patients who have been followed for at least 5 years, 72% have inactive disease as defined by ACR Pedi 90 criteria off therapy. Another 20% have inactive disease on therapy, which is anakinra or another biologic in most cases. The majority of patients have avoided corticosteroids completely.
Freedom from corticosteroids has been accompanied by high rates of satisfaction and has allowed patients to avoid adverse events associated with corticosteroids. For example, only one patient in this series has a growth curve more than two standard deviations below normal for age and gender, according to Dr. Vastert.
“This is just a single-center cohort study, but we now have 3 more years of data to be convinced of this concept,” Dr. Vastert said.
Another notable finding from this cohort: 12 patients have been enrolled that did not fulfill International League of Associations for Rheumatology criteria for systemic JIA because of the absence of joint involvement. Strongly suspected of having systemic JIA because of other clinical signs and features, these patients have also responded well to first-line anakinra therapy.
“Our data point to a classification [of systemic JIA] that does not include arthritis as a prerequisite for diagnosis,” said Dr. Vastert, who provided data suggesting that elevated levels of IL-18 might be among biomarkers that could be employed in a revised classification system.
The study was not funded by industry. Dr. Vastert reported receiving consulting fees from Novartis.