Background/Purpose: Tumor Necrosis Factor Receptor-Associated Periodic Fever Syndrome (TRAPS) is an autoinflammatory disease inherited in an autosomal dominant fashion.  TRAPS develops secondary to mutations in TNFRSF1A. Associated symptoms include periodic attacks of peritonitis, constipation, arthritis in large joints, arthralgia, migratory rash with underlying myalgia, periorbital edema, conjunctivitis, splenomegaly, and increased risk for AA amyloid deposition. Typically, attacks last from days to weeks. The common treatment modalities are corticosteroids, the p75:Fc fusion protein, etanercept, and IL-1 antagonists. Recent studies suggest that multiple cytokines are involved in the pathogenesis of TRAPS. To date, there are limited data comparing the efficacy of etanercept and IL-1 inhibitors in TRAPS. To explore this, we have analyzed the response of seven patients with TRAPS who were transitioned from etanercept to anakinra due to modest response while on etanercept.

Methods: CRP and ESR were measured serially in seven patients with TRAPS who had been initially treated with etanercept and were subsequently switched to anakinra. Patient records were evaluated for clinical and laboratory associations.  Patients with the R92Q and P46L variants were excluded from our analysis.

Results: Seven adult patients with TRAPS were switched from etanercept to anakinra therapy due to poor symptom control and persistent elevation in inflammatory markers. Among all seven patients, the range of ESR before starting anakinra (no patients were actively flaring at the time labs were drawn) was 37-91 mm/hr and after was 5-18 mm/hr. The range of CRP before starting anakinra was 18.10-186 mg/L and after was <0.5-8.85 mg/L. The etanercept doses ranged from 50mg weekly to 75mg weekly. The anakinra doses ranged from 100mg daily to 300mg daily. One patient with AA amyloidosis had normalization of proteinuria and stabilization of creatinine within 16 months of starting anakinra.  Patients reported fewer flares, shorter duration of flares, and decreased necessity for additional medications during flares (corticosteroids and narcotics).

Conclusion: Our findings indicate that in some patients, anakinra therapy is superior to etanercept therapy for TRAPS. Of the seven patients, all of them experienced clinically significant decreases in inflammatory markers including CRP and ESR as well as clinical improvement in symptoms related to TRAPS upon the initiation of anakinra.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-anakinra-therapy-in-seven-adults-after-suboptimal-response-to-etanercept-therapy-for-tumor-necrosis-factor-receptor-associated-periodic-fever-syndrome/