Role of Etanercept in the Treatment of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome: Personal Experience and Review of the Literature

Abstract

Tumor necrosis factor-α receptor (TNFRl)—associated periodic syndrome (TRAPS) is the most common autosomal-dominant autoinflammatory condition and is caused by mutations in the TNFRSF1A gene. TRAPS is characterized by recurrent attacks of fever typically lasting from 1 to 3 weeks; in addition to fever, common clinical features include mainly periorbital oedema, conjunctivitis, a migratory erythematous plaque simulating erysipela with underlying myalgia, and arthritis or arthralgia; serosal membrane inflammation is also possible. The identification of TNFRSF1A mutations as the genetic cause of TRAPS coincided with the wider use of biological agents in medicine and raised the possibility that blocking TNF could potentially represent the primary therapeutic goal in TRAPS, thus disclosing new treatment choices for this complex disease. In the past few years, isolated reports and case-series have been published suggesting that inhibition of TNF-α might represent a promising therapeutic approach in TRAPS. We present here our experience with etanercept in the treatment of patients affected with TRAPS, and we also add a review of the literature.

Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS)

“…Among biologic agents, the TNF-blocker etanercept initially yielded promising results [8][9][10]; however, the efficacy may decline over time [11,12], and resistant patients have also been reported [13]. On the contrary, the chimeric anti-TNF monoclonal antibody infliximab and the fully human anti-TNF monoclonal antibody adalimumab can induce a paradoxical disease flare [12,14].…”

Clues to detect tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study

“…The identification of genetically-positive IRAP patients would also allow-in the case of poor response to conventional therapies-to prescribe more specific treatments, based on the recent experience acquired in the management of AID, and particularly in the treatment of patients with TRAPS [12,13,15,16].…”

“…Lowpenetrance TNFRSF1A mutations may cause oligosymptomatic TRAPS, with episodes of fever lasting only a few days and a lower intensity of disease-associated symptoms. In addition, subjects carrying low-penetrance alleles and characterized by a late disease onset may display recurrent pericarditis as the only clinical manifestation, hindering differential diagnosis between TRAPS and IRAP [9,[12][13][14][15][16].…”

Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis

“…Patients generally display periodically-recurring inflammatory phenomena which have a typical onset in the pediatric age, and classically show increased inflammatory parameters, alternating with symptom-free intervals in which acute-phase reactants are normal [58]. Despite the common pathogenetic mechanisms and the intermittent timing, all autoinflammatory disorders have distinct features and specific therapeutic options, which emphasize the need for a specific diagnosis in each case [59][60][61][62][63]. IL-1 blocking therapies are dramatically effective at controlling organ disease and damage in patients with various autoinflammatory disorders, and different strategies to block IL-1 have been used in clinical trials, displaying a substantial success in bringing down episodes of fever and elevations in acute-phase reactants [64][65][66][67] and this may also extend to other conditions with acute inflammation, such as gouty arthritis or heart disease.…”