[ACR22] Paediatric Rheumatology

Author: Thomas Renson

Ramanan et al (2210) presented phase 3 efficacy and safety data of baricitinib in 220 (non-systemic) juvenile idiopathic arthritis (JIA) patients. 63.5% of the patients achieved a week 12 JIA-ACR50 response with 46.1% and 20.1% having a JIA-ACR70/90 response, respectively. During the double-blind withdrawal phase, baricitinib increased the time to flare (HR 0.24 [95% CI 0.13-0.45], p<0.001) and decreased the proportion of patients having a flare (17.1% vs 50.6%, p<0.001) compared to placebo.

Lee et al (004) established the role of mTORC1 as a driver of inflammation in systemic juvenile idiopathic arthritis (sJIA) and macrophage activation syndrome (MAS). An mTORC1 gene signature in IL-1 receptor antagonist knockout mice was demonstrated by single-cell RNA sequencing. Disease activity in these mice was attenuated following mTORC1 inhibition by rapamycin. Subsequently, further upregulation of mTORC1 in sJIA patients with MAS was demonstrated. Finally, knockout of TSC2 in mice leads to an overactivation of mTORC1 and spontaneous development of MAS. This study shows how the mTORC1 pathway connects the pathophysiology of sJIA and MAS.

Almeida de Jesus et al (0567) described a novel autoinflammatory disease caused by gain-of-function mutations in lyn kinase. Three patients with de novo LYN mutations in p.Y508 were included. All presented with systemic inflammation, perinatal neutrophilic small vessel vasculitis, periorbital edema, hepatosplenomegaly, and abdominal and testicular pain. Two out of three patients presented with early onset liver fibrosis. The disease was therefore named Lyn associated vasculopathy and liver fibrosis (LAVLI).

Weiss et al (0852) aimed to develop classification criteria for juvenile spondyloarthritis (jSpA) patients with axial involvement using an iterative approach guided by an expert panel. 304 jSpA patients with suspected axial involvement were recruited from six international centers. Magnetic resonance imaging (MRI) typical for sacroiliitis was deemed necessary, but not sufficient, for fulfillment of the classification criteria. Furthermore, active inflammation and structural lesions on MRI were the most heavily weighted domains.

Ogbu et al (0875) identified blood-based biomarkers predicting treatment response of tofacitinib in 166 patients with distinct JIA subtypes. Baseline levels of IL-18 and decreasing levels of S100A12 and MCP-1 during follow-up were excellent predictors of JIA-ACR90 response at week 18 following treatment with tofacitinib (AUC 0.78 [95% CI 0.70-0.87]).

Vastert et al. (L12) explored the efficacy of anakinra as a first-line treatment for sJIA in the context of  HLA-DRB1*15 haplotypes, which have been associated with adverse drug reactions including sJIA-related interstitial lung disease (sJIA-LD). One out of 65 patients (1.5%) developed sJIA-LD. Anakinra demonstrated efficacy irrespective of HLA-DRB1*15 background and should therefore not be withheld.

Wang et al (0514) compared renal response outcomes of juvenile patients with proliferative lupus nephritis treated with EuroLupus versus NIH cyclophosphamide dosing regimen. No significant differences were found between both strategies in reaching at least a partial renal response (OR 0.79 [95% CI 0.34-1.87], p=0.60) and a complete renal response (OR 0.80 [95% CI 0.30-2.11], p=0.65) at 12 months.

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