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22-03-2022 | Juvenile idiopathic arthritis | News

Data support biomarker-guided therapy withdrawal in JIA

Author: Laura Cowen


medwireNews: Withdrawing therapy on the basis of low levels of high-sensitivity C-reactive protein (hsCRP) and the calcium-binding protein S100A12 may be a feasible approach for young people with juvenile idiopathic arthritis (JIA) in remission, PREVENT-JIA study data show.

Writing in the Annals of the Rheumatic Diseases, Dirk Foell (University Hospital Munster, Germany) and co-authors say their findings suggest “that using predictive markers of subclinical inflammation is a promising tool in the decision-making process of therapy withdrawal, which translates into direct benefit for patients.”

The PREVENT-JIA trial included 100 participants with JIA who had been in clinical remission on stable medication for at least 6 months.

Of these, 82 had hsCRP and S100A12 levels that were considered low risk for relapse at the first measurement, that is below 0.3 mg/dL for hsCRP and below 175 ng/mL for S100A12 initially and then 75 ng/mL following the development of an assay with improved sensitivity.

These patients, along with nine more who were considered low risk at later visits, stopped conventional and/or biologic DMARD therapy and were followed up for 12 months.

During follow-up, 41 (45%) participants experienced a flare. In addition, there were eight flares and one dropout recorded among the nine participants who continued maintenance therapy because their biomarkers remained above the cutoff, giving a total flare rate of 49%.

By comparison, the flare rate was significantly higher among 100 matched participants from the German BiKeR pharmacovigilance registry, at 62%, and a hazard ratio (HR) of 0.67. This corresponded to a number needed to treat to avoid one JIA flare by measuring biomarkers of eight.

The flare rate in the 25 participants in the matched BiKeR cohort who withdrew therapy without biomarker-based stratification was 60%.

In addition, the researchers calculated that “[p]atients in the PREVENT-JIA study revealed a significantly lower cumulative flare rate following therapy withdrawal and therefore a significantly longer time from stopping medication until first flare compared with patients from the BiKeR registry.” The adjusted HR for a flare following withdrawal was 0.62, in favor of the biomarker-guided PREVENT-JIA cohort.

Foell et al also found that the duration of therapy was significantly shorter in the PREVENT-JIA cohort than in the BiKeR group, but they stress that differences in the characteristics of the two groups have to be taken into account when considering their findings.

In particular, fewer patients in the PREVENT-JIA cohort were using biologics that in the BiKeR group “and literature suggests that there is a higher flare risk following withdrawal of [biologics] versus other agents,” they remark.

Nonetheless, the authors conclude that using “S100A12/high-sensitivity C-reactive protein as markers of subclinical inflammation may help to evaluate the risk of flares and guide treatment decision.”

“A risk-adapted strategy reduces both number of flares in remission and the cumulative drug exposure compared with standard-of-care practice,” they add.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Ann Rheum Dis 2022; doi:10.1136/annrheumdis-2021-222029