Abstract
Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response.Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers.Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy (p < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment (p < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period (p < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids (p = 0.025) and in the dosages employed (p < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate (p < 0.0001), C reactive protein (p < 0.0001), serum amyloid A (p < 0.0001), and in the 24-h proteinuria dosage during follow-up (p = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001–0.841, p = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301–0.953, p = 0.034) were significantly associated with a complete response. No serious adverse events were observed.Conclusions: Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.
Highlights
Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disease caused by mutations of the TNFRSF1A gene, encoding for the tumor necrosis factor (TNF)-α receptor 1
Patients were enrolled in 16 Italian tertiary Centers participating to the AutoInflammatory Disease Alliance (AIDA) network; all patients had been diagnosed with TRAPS on the basis of genetic analysis (Sanger sequencing of TNFRSF1A gene or generation sequencing) performed in subjects presenting with recurrent fever attacks and other inflammatory manifestations evocative of TRAPS
Biologic agents used in TRAPS patients enrolled in the present study were: the IL-1 receptor antagonist anakinra; the fully humanized IgG1 monoclonal antibody acting against IL-1β canakinumab; the fusion protein of the TNF-α receptor and the Fc region of human IgG1 etanercept; the chimeric antiTNF-α monoclonal antibody infliximab; the fully humanized monoclonal antibody against human TNF-α adalimumab; and the humanized monoclonal antibody that binds to both soluble and membrane-bound IL-6 receptors tocilizumab
Summary
Tumor necrosis factor receptor associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disease caused by mutations of the TNFRSF1A gene, encoding for the tumor necrosis factor (TNF)-α receptor 1. Despite the protean clinical spectrum, based on data from the Eurofever Registry, Gattorno et al have recently proposed clinical and genetic criteria aimed at classifying TRAPS patients depending on the genotype (confirmatory or not confirmatory) or, in cases with no data about genetic analysis, according to the presence or absence of specific clinical manifestations. These criteria were primarily built for research and scientific purposes rather than for a direct application in clinical practice [5]. The therapy of TRAPS should allow an easy participation in daily activities and improvement of healthrelated quality of life [6]
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