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Extended report
Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review
  1. Nienke ter Haar1,
  2. Helen Lachmann2,
  3. Seza Özen3,
  4. Pat Woo4,
  5. Yosef Uziel5,
  6. Consuelo Modesto6,
  7. Isabelle Koné-Paut7,
  8. Luca Cantarini8,
  9. Antonella Insalaco9,
  10. Bénédicte Neven10,
  11. Michael Hofer11,
  12. Donato Rigante12,
  13. Sulaiman Al-Mayouf13,
  14. Isabelle Touitou14,
  15. Romina Gallizzi15,
  16. Efimia Papadopoulou-Alataki16,
  17. Silvana Martino17,
  18. Jasmin Kuemmerle-Deschner18,
  19. Laura Obici19,
  20. Nicolae Iagaru20,
  21. Anna Simon21,
  22. Susan Nielsen22,
  23. Alberto Martini23,
  24. Nicolino Ruperto24,
  25. Marco Gattorno24,*,
  26. Joost Frenkel1,*,
  27. Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever/Eurotraps Projects”
  1. 1Department of Paediatrics, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2National Amyloidosis Centre, Royal Free Campus, University College London Medical School, London, UK
  3. 3Department of Pediatric Nephrology and Rheumatology, Hacettepe University, Ankara, Turkey
  4. 4Center of Paediatric and Adolescent Rheumatology, University College London, London, UK
  5. 5Department of Pediatrics, Meir Medical Centre, Kfar Saba, Israel
  6. 6Reumatologia, Hospital Valle de Hebron, Barcelona, Spain
  7. 7Centre de reference national des maladies auto-inflammatoires, CEREMAI, rhumatologie pediatrique, CHU Le Kremlin Bicetre (University of Paris SUD), Le kremlin Bicetre (Paris), France
  8. 8Rheumatology Unit, Policlinico le Scotte, University of Siena, Siena, Italy
  9. 9Reumatologia, Ospedale Pediatrico Bambin Gesu', Roma, Italy
  10. 10Centre de référence national pour les Arthrites Juveniles, Unité d’Immunologie, Hématologie et Rhumatologie Pediatrique, Université Paris-Descartes, Hôpital Necker-Enfants Malades, Paris, France
  11. 11Paediatrie, Centre Multisite Romand de Rhumatologie Pediatrique/Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
  12. 12Department of Pediatric Sciences, Università Cattolica del Sacro Cuore, Roma, Italy
  13. 13Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  14. 14Unit of AutoInflamatory diseases CHU Montpellier, UM1, INSERM U844, Montpellier, France
  15. 15UOC Genetic and Pediatric Immunology, Department of Pediatrics, University of Messina, Messina, Italy
  16. 16Fourth Department of Pediatrics, Aristotle University of Thessaloniki Papageorgiou Hospital, Thessaloniki, Greece
  17. di Scienze Pediatriche e dell'Adolescenza, Clinica Pediatrica Universita' di Torino, Torino, Italy
  18. 18Universitatsklinik fur Kinderheilkunde und Jugendmedizin, Tuebingen, Germany
  19. 19Amyloid Centre, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
  20. 20Clinica II pediatrie, Institute for Mother and Child Care, Bucharest, Romania
  21. 21Department of General Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
  22. 22Pediatrisk klinik II, Juliane Marie Centret, Rigshospitalet, København, Denmark
  23. 23Istituto Giannina Gaslini, Pediatria II, Reumatologia and Universià degli Studi di Genova, Genova, Italy
  24. 24Istituto Giannina Gaslini, Pediatria II, Reumatologia, Genova, Italy
  1. Correspondence to Marco Gattorno, Istituto Giannina Gaslini, Pediatria II – Reumatologia, Genova 16147, Italy; marcogattorno{at}
  • * MG and JF contributed equally to this study.


Objective To evaluate the response to treatment of autoinflammatory diseases from an international registry and an up-to-date literature review.

Methods The response to treatment was studied in a web-based registry in which clinical information on anonymised patients with autoinflammatory diseases was collected retrospectively as part of the Eurofever initiative. Participating hospitals included paediatric rheumatology centres of the Paediatric Rheumatology International Trial Organisation network and adult centres with a specific interest in autoinflammatory diseases. The following diseases were included: familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF)-receptor associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), pyogenic arthritis pustulosis acne (PAPA) syndrome, deficiency of interleukin-1 receptor antagonist (DIRA), NLRP12-related periodic fever and periodic fever aphthosis pharyngitis adenitis (PFAPA) syndrome. Cases were independently validated by experts for each disease. A literature search regarding treatment of the abovementioned diseases was also performed using Medline and Embase.

Results 22 months from the beginning of the enrolment, complete information on 496 validated patients was available. Data from the registry in combination with evidence from the literature confirmed that colchicine is the treatment of choice for FMF and IL-1 blockade for DIRA and CAPS. Corticosteroids on demand probably represent a valid therapeutic strategy for PFAPA, but also for MKD and TRAPS. Patients with poorly controlled MKD, TRAPS, PAPA or FMF may benefit from IL-1 blockade; anti-TNF treatment may represent a possible valuable alternative.

Conclusions In the absence of high-grade evidence, these results could serve as a basis for therapeutic guidelines and to identify candidate drugs for future therapeutic trials.

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  • Funding This project is supported by the Executive Agency for Health and Consumers of the European Union (EAHC, Project No2007332) and by Coordination Theme 1 (Health) of the European Community's FP7, grant agreement number HEALTH-F2-2008-200923. Unrestricted educational grants were also kindly provided by PRINTO and Novartis.

  • Competing interests The Gaslini Hospital, which is the public hospital where NR, MG and AM work as full-time employees, has received contributions to support PRINTO and Eurofever research activities from Abbott, ACRAF, Astra Zeneca, Bristol Myers and Squibb, Centocor Research & Development, Eli Lilly and Company, ‘Francesco Angelini’, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwartz Biosciences, Wyeth Pharmaceuticals and Xoma. NR and AM have received payment for service on speakers' bureaus from Astra Zeneca, Bristol Myers and Squibb, Janssen Biologics BV, Roche and Wyeth/Pfizer. LO and SO have received consultancy fees from Novartis. IK-P has received consultancy fees from Novartis, SOBI Biovitrum, Roche, Abbot, Pfizer and research grants from LFB and SOBI Biovitrum. AS has received consultancy fees from Novartis and SOBI Biovitrum. HL and JF have received honoraria for meeting presentations from Novartis and SOBI Biovitrum. JK-D has received consultancy fees from Novartis, SOBI Biovitrum and Roche and research grants and speaker fees from Novartis. MH has received honoraria for meeting presentations from Novartis and Pfizer. MG has received consultancy fees and honoraria for meeting presentations from Novartis and SOBI Biovitrum.

  • Ethics approval Ethics approval was obtained from the ethical board of the G Gaslini Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.