Title : Not So Idiopathic After All: Genotype, Phenotype and IL-1 Blockade Response Converge in Recurrent Pericarditis
Abstract:
Recurrent pericarditis (RP), historically labeled "idiopathic," is increasingly recognized as an NLRP3 inflammasome/interleukin-1 (IL-1)–driven autoinflammatory syndrome[cite: 6]. This study quantitatively synthesizes genetic-architecture and IL-1 blockade trial data in idiopathic/recurrent pericarditis (IRP/RP) to evaluate the case for genotype- and biomarker-informed treatment selection.
A structured search (PubMed/Embase, 2010–2026) was conducted for next-generation/whole-exome sequencing (NGS/WES) autoinflammatory gene screening cohorts and randomized controlled trials (RCTs) of IL-1 blockade. Pooled NGS/WES cohorts (n=366) demonstrated inflammatory-gene variants in 14.8–22.9% of patients, with MEFVsignificantly enriched compared to reference controls (P=0.040). Genetically positive patients exhibited higher rates of fever (76.7% vs. 49.5%) and elevated CRP (93.3% vs. 77.2%). Independent RCTs (AIRTRIP, RHAPSODY, goflikicept phase II/III) demonstrated striking, concordant reductions in recurrence risk with IL-1 blockade (up to 96% risk reduction, all P<0.001). These findings confirm that genetic and clinical trial evidence converge on a reproducible autoinflammatory IL-1 axis, strongly supporting precision-guided management in RP.
