Pietro Leccese1, Yesim Ozguler2, Robin Christensen3, Sinem Nihal Esatoglu2, Dongsik Bang4, Bahram Bodaghi5, Aykut Ferhat Celik6, Farida Fortune7, Julien Gaudric8, Ahmet Gül9, Ina Kötter10, Alfred Mahr11, Robert J Moots12, Jutta Richter13, David Saadoun14, Carlo Salvarani15, Francesco Scuderi16, Petros P Sfikakis17, Aksel Siva18, Miles Stanford19, Ilknur Tugal-Tutkun20, Richard West21, Sebahattin Yurdakul2, Ignazio Olivieri22, Hasan Yazici2, Gulen Hatemi23. 1. 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. 2. Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul 34098, Turkey. 3. Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital & Department of Rheumatology, Odense University Hospital, Copenhagen, Denmark. 4. Department of Dermatology, Catholic Kwandong University International St. Mary's Hospital, Incheon, Korea. 5. Department of Ophthalmology, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. 6. Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 7. Centre for Clinical and Diagnostic Oral Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, and the London Behçet's Centre, Barts Health London, London, United Kingdom. 8. Department of Vascular Surgery, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. 9. Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 10. Asklepios Clinic Altona, Department of Rheumatology, Immunology and Nephrology, Hamburg, Germany. 11. Department of Internal Medicine, Hospital Saint-Louis, Paris, France. 12. National Behcet's Syndrome Centre of Excellence, Aintree University Hospital, Liverpool, UK. 13. Institute for Haematopathology Hamburg, Hamburg, Germany. 14. Department of Inflammation-Immunopathology-Biotherapy, Sorbonne Universités, UPMC Univ Paris 06, Paris, France; INSERM, Paris, France; CNRS, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Centre de Référence des Maladies Auto-Immunes et Systémiques Rares, Centre de Référence des Maladies Auto-Inflammatoires, Paris, France. 15. Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Italy. 16. Patient Research Partner, Catania, Italy. 17. First Department of Propaedeutic and Internal Medicine & Rheumatology Unit, National Kapodistrian University of Athens Medical School, Athens, Greece. 18. Department of Neurology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. 19. Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. 20. Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 21. patient research partner, member of the UK Behcet's Syndrome Society and Director of Behcets International, London, United Kingdom. 22. Rheumatology Institute of Lucania (IRel) and the Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, and the Basilicata Ricerca Biomedica (BRB) Foundation, Potenza and Matera, Italy. 23. Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul 34098, Turkey. Electronic address: gulenhatemi@yahoo.com.
Abstract
OBJECTIVES: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS. METHODS: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes. RESULTS: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study. CONCLUSIONS: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results.
OBJECTIVES: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS. METHODS: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes. RESULTS: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study. CONCLUSIONS: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results.