Yesim Ozguler1, Pietro Leccese2, Robin Christensen3,4, Sinem Nihal Esatoglu1, Dongsik Bang5, Bahram Bodaghi6, Aykut Ferhat Çelik7, Farida Fortune8,9, Julien Gaudric10, Ahmet Gul11, Ina Kötter12, Alfred Mahr13, Robert J Moots14, Jutta Richter15, David Saadoun16,17,18,19, Carlo Salvarani20, Francesco Scuderi21, Petros P Sfikakis22, Aksel Siva23, Miles Stanford24, Ilknur Tugal-Tutkun25, Richard West26, Sebahattin Yurdakul1, Ignazio Olivieri2,27, Hasan Yazici1, Gulen Hatemi1. 1. Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 2. Rheumatology Institute of Lucania (IRel) and the Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza and Matera, Italy. 3. Bispebjerg and Frederiksberg Hospital, Musculoskeletal Statistics Unit, The Parker Institute, Copenhagen, Denmark. 4. Department of Rheumatology, Odense University Hospital, Copenhagen, Denmark. 5. Department of Dermatology, Catholic Kwandong University International St Mary's Hospital, Incheon, Korea. 6. Department of Ophthalmology, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. 7. Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 8. Centre for Clinical and Diagnostic Oral Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. 9. The London Behçet's Centre, Barts Health London, London, UK. 10. Department of Vascular Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. 11. Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 12. Asklepios Clinic Altona, Department of Rheumatology, Immunology and Nephrology, Hamburg, Germany. 13. Department of Internal Medicine, Hospital Saint-Louis, Paris, France. 14. National Behcet's Syndrome Centre of Excellence, Aintree University Hospital, Liverpool, UK. 15. Institute for Haematopathology Hamburg, Hamburg, Germany. 16. Department of Inflammation-Immunopathology-Biotherapy, Sorbonne Universités, UPMC Univ Paris 06, Paris, France. 17. INSERM, Paris, France. 18. CNRS, Paris, France. 19. Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 20. Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Italy. 21. Patient Research Partner, Catania, Italy. 22. First Department of Propaedeutic and Internal Medicine & Rheumatology Unit, National Kapodistrian University of Athens Medical School, Athens, Greece. 23. Department of Neurology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 24. Department of Ophthalmology, St Thomas' Hospital, London, UK. 25. Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 26. Member of the UK Behcet's Syndrome Society and Director of Behcets International, Patient Research Partner, London, UK. 27. Basilicata Ricerca Biomedica (BRB) Foundation, Potenza and Matera, Italy.
Abstract
Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. Results: We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. Conclusion: The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.
Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. Results: We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. Conclusion: The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.