title: International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome.
abstract: Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS).
  
  
  
  PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment.
  
  
  
  A total of 134 patients were analyzed: FMF (n = 49), TRAPS (n = 47), and MKD/HIDS (n = 38). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P = 0.03 and P < 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts.
  
  
  
  Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further refinement of treatment practices.
authors.affiliation: Hacettepe University, Ankara, Turkey.
authors.forename: Seza
authors.initials: S
authors.lastname: Ozen
authors.affiliation: University Children's Hospital, Tuebingen, Germany.
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
authors.affiliation: Ospedale A. Meyer, Firenze, Italy.
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.affiliation: Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
authors.affiliation: Hôpital Necker, Assistance Publique Hopitaux de Paris, IMAGINE Institute, and Paris-Descartes University, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Quartier
authors.affiliation: Versailles Hospital, Le Chesnay, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Kone-Paut
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zeft
authors.affiliation: Phoenix Children's Hospital, Phoenix, Arizona.
authors.forename: Steve
authors.initials: S
authors.lastname: Spalding
authors.affiliation: Istanbul School of Medicine, University of Istanbul, Istanbul, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gul
authors.affiliation: Centre Hospitalier Universitaire de Bicêtre, APHP, University of Paris SUD, Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Hentgen
authors.affiliation: Leeds Teaching Hospital, Leeds, UK.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Savic
authors.affiliation: Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.affiliation: University Medical Center, Utrecht, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Frenkel
authors.affiliation: University of Siena, Siena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cantarini
authors.affiliation: Navigant Consulting, London, UK.
authors.forename: Dony
authors.initials: D
authors.lastname: Patel
authors.affiliation: Navigant Consulting, London, UK.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Weiss
authors.affiliation: Navigant Consulting, London, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Marinsek
authors.affiliation: Navigant Consulting, London, UK.
authors.forename: Ravi
authors.initials: R
authors.lastname: Degun
authors.affiliation: Novartis Pharmaceuticals, East Hanover, New Jersey.
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Lomax
authors.affiliation: University College London, London, UK.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Lachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D057210:Delayed Diagnosis / Q000639:trends; D057286:Electronic Health Records; D005060:Europe / Q000453:epidemiology; D010505:Familial Mediterranean Fever / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005334:Fever / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D056660:Hereditary Autoinflammatory Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000639:trends*; D011237:Predictive Value of Tests; D012017:Referral and Consultation / Q000639:trends; D012189:Retrospective Studies; D012219:Rheumatology / Q000639:trends*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products