4CPS-130 One in a million: a TNF receptor-1 associated syndrome resistant to anti-TNF-alpha therapy

Background and importanceTumour necrosis factor receptor associated periodic syndrome (TRAPS) is a rare disorder with a prevalence of approximately 1 per million. The goal of therapy is prevention of recurrent symptoms and normalisation of inflammatory markers. These patients also have an increased risk of developing amyloidosis. Clinical experience and extrapolation from other autoinflammatory disorders suggest that early institution of biologics can lowers this risk. Historically, antitumour necrosis factor (TNF) therapy (etanercept) was used for patients with frequent and/or severe recurrences and for those with TNF receptor-1 (TNFR1) gene mutations associated with a high risk of amyloidosis.Aim and objectivesTo improve evidence about TRAPS refractory to anti-TNFs and its management.Material and methodsWe describe the case of a child affected by TRAPS and its pharmacotherapeutic management. Treatment options included oral glucocorticoids and biologic agents (etanercept, anakinra). Medical and pharmaceutical records were reviewed, and a bibliographic research was made to establish the state of the art treatment of TRAPS. UpToDate, Pubmed and the Cochrane Library were consulted, finding little information on this very rare medical condition.ResultsOur patient was a 7 year old boy who presented with recurrent febrile episodes, accompanied by abdominal pain and periorbital eczema. There was no infectious focus. Laboratory data showed elevated inflammatory markers. The rheumatologist suspected an autoimmune syndrome rather than an autoinflammatory disease. Lack of autoantibodies and a genetic diagnosis confirmed TRAPS.Initial treatment was oral prednisone, with a response similar to NSAIDs. Due to persistence of symptomatology, the clinician indicated etanercept, which achieved a partial response but had to be interrupted because of respiratory related sepsis. Afterwards, this biologic was reintroduced with low doses of prednisone. Over the following months the patient relapsed, and anakinra was prescribed instead of etanercept. Anakinra treatment showed satisfactory results, achieving symptomatology control and normalisation of laboratory parameters with no remarkable safety concerns.Conclusion and relevanceWe have presented the case of a patient refractory to anti-TNF treatment who experienced dramatic improvement with the recombinant human IL-1 receptor antagonist anakinra. There are only a few cases published on this subject, and our experience supports