Predictors of Effectiveness of Anakinra in Systemic Juvenile Idiopathic Arthritis

Abstract

Objective.To seek predictors of therapeutic response to the interleukin (IL)-1 inhibitor anakinra in children with systemic-onset juvenile idiopathic arthritis (sJIA).Methods.The clinical charts of all patients with sJIA who were newly treated with anakinra at our center between 2004 and 2017 were reviewed retrospectively. Predictors included baseline demographic, clinical, and laboratory variables as well as previous or concomitant therapies. The effectiveness of anakinra was assessed at 1 year after treatment start. Complete clinical response (CCR) was defined as absence of fever, physician’s global assessment ≤ 1, count of active joints ≤ 1, negative C-reactive protein, and ≥ 75% reduction of corticosteroid dose. According to the intention-to-treat principle, patients who had anakinra discontinued before 1 year for any reasons other than disease remission were classified as nonresponders. Statistics included univariate and multivariable analyses.Results.Of the 62 patients included in the study, 24 (39%) met the criteria for CCR at 1 year, whereas 38 (61%) did not. On multivariable analysis, independent correlations with achievement of CCR were identified for shorter disease duration, lower active joint count, higher ferritin level, and greater activity of systemic manifestations. The area under the curve of the model was 0.83.Conclusion.Our findings help to delineate the clinical profile of patients with sJIA who are more likely to benefit from IL-1 blockade. They also underscore the need for studies aimed at examining the therapeutic role of early IL-1 inhibition and to identify biomarkers predicting response to either IL-1 or IL-6 antagonists.

Comparison of Early vs. Delayed Anakinra Treatment in Patients With Adult Onset Still's Disease and Effect on Clinical and Laboratory Outcomes

“…In addition, at the 6-month visit the number of swollen joints was significantly lower among patients starting ANK as first-line treatment than among subjects treated with cDMARDs first. This finding seems to reconnect with a previous experience in SOJIA patients supporting a better treatment outcome among patients with no previous anti-TNF-α medications (27). In this regard, since a higher number of treatment lines generally reflects a longer disease history, the results obtained in our study seem to highlight a faster resolution of articular involvement in patients undergoing ANK during the first months of treatment.…”

“…Therefore, the identification of clinical or laboratory predictors of response currently accounts for a primary need to establish when and to whom IL-1 inhibitors should be started. In this regard, an early treatment with IL-1 blockade has been associated with a better outcome in the pediatric context (25)(26)(27)(28).…”

Testing the Model for Predicting Effectiveness of Anakinra in Systemic Juvenile Idiopathic Arthritis

“…The rate of CCR1 in our sJIA cohort (62.2%) is in the high range among the rates (31-85%) reported in previous studies 1,3,4,5,6,7 . In our patients, the number of active joints at initiation of anakinra was significantly higher in complete responders compared to nonresponders, and the model proposed by Saccamanno, et al 1 seems to be associated with higher rate of CCR1.…”

“…Flares under anakinra treatment were more frequently observed among nonresponders than complete responders. The model proposed by Saccomanno, et al 1 was tested in all patients ( Table 2). Significantly higher numbers of complete responders than nonresponders met all 4 variables (67.9% vs 8.3%, respectively; p = 0.001).…”

Current Review of Systemic Juvenile Idiopathic Arthritis: What Do Paediatricians Need to Know?

“…A summary of currently used biologics for systemic JIA. profile: shorter disease duration, presence of a higher degree of systemic manifestations, higher ferritin and neutrophil count and lower active joints at the start and early complete response to anakinra at 1 month[72] [73][74]. On the basis of the growing evidence on anakinra's effectiveness and safety profile, the relative ease of administration and the feasibility of using the medication at home, anakinra has become the first option to treat sJIA, when it is affordable, to…”