Efficacy of etanercept in the tumor necrosis factor receptor-associated periodic syndrome: A prospective, open-label, dose-escalation study

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 64; no. 3; pp. 908 - 913
• Main Authors: Bulua, Ariel C., Mogul, Douglas B., Aksentijevich, Ivona, Singh, Harjot, He, David Y., Muenz, Larry R., Ward, Michael M., Yarboro, Cheryl H., Kastner, Daniel L., Siegel, Richard M., Hull, Keith M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Biological and medical sciences; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Drug Substitution; Drug therapy; Errors of metabolism; Etanercept; Familial Mediterranean Fever - drug therapy; Humans; Immunoglobulin G - therapeutic use; Immunologic Factors - therapeutic use; Inflammatory joint diseases; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical research; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Prospective Studies; Receptors, Tumor Necrosis Factor - therapeutic use; Receptors, Tumor Necrosis Factor, Type I; Remission Induction; Treatment Outcome; Immunomodulator; Etanercept; Antipsoriatic agent; Rheumatology; Tumor necrosis factor receptor-associated periodic syndrome; Hereditary periodic fever; Dose; Genetic disease; Inflammatory disease
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.33416

Objective
To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor–associated periodic syndrome (TRAPS).
Methods
Fifteen patients with TRAPS were enrolled in a prospective, open‐label, dose‐escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute‐phase reactants. Between 7 years and 9 years after the conclusion of the initial study, patients completed a followup survey and were evaluated to determine the long‐term outcome of etanercept treatment.
Results
Etanercept treatment significantly attenuated the total symptom score and reduced the frequency of symptoms. Etanercept also reduced levels of acute‐phase reactants, particularly during asymptomatic periods. During a 10‐year followup period, patients continued to receive etanercept for a median of 3.3 years, with a number of patients switching to anti–interleukin‐1β receptor therapy or not receiving biologic agents, most frequently citing injection site reactions and lack of efficacy as reasons for discontinuation. However, patients continuing to receive etanercept had reduced symptoms at followup.
Conclusion
Etanercept reduces symptoms and serum levels of inflammatory markers of TRAPS in a dose‐dependent manner, but does not completely normalize symptoms or acute‐phase reactant levels. Although long‐term adherence to etanercept is poor, continuing to receive etanercept may provide continued symptomatic benefit.