Matheus Vieira1,2,3,4, Solène Buffier1,2,3,4, Mathieu Vautier1,2,3,4, Alexandre Le Joncour1,2,3,4, Yvan Jamilloux5, Mathieu Gerfaud-Valentin5, Laurence Bouillet6,7, Estibaliz Lazaro8, Stéphane Barete9,10,11, Laurent Misery12, Delphine Gobert13, Tiphaine Goulenok14, Olivier Fain13, Karim Sacre14, Pascal Sève5, Patrice Cacoub1,2,3,4, Cloé Comarmond1,2,3,4, David Saadoun1,2,3,4. 1. Sorbonne Universités AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, Paris, France. 2. Centre National de Références Maladies Autoimmunes Systémiques Rares, Centre National de Références Maladies Autoinflammatoires et Amylose Inflammatoire, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France. 3. Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France. 4. INSERM 959, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France. 5. Department of Internal Medicine, Hopital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France. 6. Service de Médecine Interne, CHUGA, Unité Inserm 1036, Université Grenoble Alpes (UGA), Grenoble, France. 7. Department of Internal Medicine, Centre de référence national des angioedèmes (CREAK), Grenoble, France. 8. Department of Internal Medicine, Haut-Lévêque Hospital, Pessac, France. 9. Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DHU i2B), Sorbonne Universités, UPMC Université Paris 06, UMR 7211, Paris, France. 10. INSERM, UMR_S 959, Paris, France. 11. UF de Dermatologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France. 12. Department of Dermatology, Brest University Hospital, Brest, France Univ Brest, Brest, France. 13. Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Faculté de Médecine Sorbonne Université, Hôpital Saint Antoine, Sorbonne Universités AP-HP, Paris, France. 14. Département de Médecine Interne, Hôpital Bichat, Assistance Publique Hôpitaux de Paris (APHP), Institut national de la santé et de la recherche médicale (INSERM) U1149, Université de Paris, Paris, France.
Abstract
Objective: Mucocutaneous and joint disorders are the most common manifestations in Behçet's syndrome (BS) and are frequently clustered in the so-called minor forms of BS. There remains a need for safe and effective treatment for joint lesions in BS. We report the long-term safety and effectiveness of apremilast in refractory joint and mucocutaneous manifestations of BS. Methods: French nationwide multicenter study including 50 BS patients with either active joint and/or mucocutaneous manifestations resistant to colchicine and/or DMARDs. Patients received apremilast 30 mg twice a day. Primary effectiveness endpoint was the proportion of patients with complete response (CR) of articular symptoms at month 6 (M6), defined as resolution of inflammatory arthralgia and arthritis, with joint count equal to zero. Results: At inclusion, the median tender and swollen joint count was of 4 [2-6] and 2 [1-2], respectively. The proportion of CR in joint disease at M6 was 65% (n = 15/23), and 17% (n = 4/23) were partial responders. CR of oral and genital ulcers, and pseudofolliculitis at M6 was 73% (n = 24/33), 94% (n = 16/17) and 71% (n = 10/14), respectively. The overall response at M6 was 74% for the entire cohort and 70% for the mucocutaneous-articular cluster (n = 27). The median Behçet's syndrome activity score significantly decreased during study period [50 (40-60) vs. 20 (0-40); p <0.0001]. After a median follow-up of 11 [6-13] months, 27 (54%) patients were still on apremilast. Reasons for apremilast withdrawal included adverse events (n = 15, 30%) and treatment failure (n = 8, 16%). Thirty-three (66%) patients experienced adverse events, mostly diarrhea (n = 19, 38%), nausea (n = 17, 34%) and headache (n = 16, 32%). Conclusion: Apremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.
Objective: Mucocutaneous and joint disorders are the most common manifestations in Behçet's syndrome (BS) and are frequently clustered in the so-called minor forms of BS. There remains a need for safe and effective treatment for joint lesions in BS. We report the long-term safety and effectiveness of apremilast in refractory joint and mucocutaneous manifestations of BS. Methods: French nationwide multicenter study including 50 BS patients with either active joint and/or mucocutaneous manifestations resistant to colchicine and/or DMARDs. Patients received apremilast 30 mg twice a day. Primary effectiveness endpoint was the proportion of patients with complete response (CR) of articular symptoms at month 6 (M6), defined as resolution of inflammatory arthralgia and arthritis, with joint count equal to zero. Results: At inclusion, the median tender and swollen joint count was of 4 [2-6] and 2 [1-2], respectively. The proportion of CR in joint disease at M6 was 65% (n = 15/23), and 17% (n = 4/23) were partial responders. CR of oral and genital ulcers, and pseudofolliculitis at M6 was 73% (n = 24/33), 94% (n = 16/17) and 71% (n = 10/14), respectively. The overall response at M6 was 74% for the entire cohort and 70% for the mucocutaneous-articular cluster (n = 27). The median Behçet's syndrome activity score significantly decreased during study period [50 (40-60) vs. 20 (0-40); p <0.0001]. After a median follow-up of 11 [6-13] months, 27 (54%) patients were still on apremilast. Reasons for apremilast withdrawal included adverse events (n = 15, 30%) and treatment failure (n = 8, 16%). Thirty-three (66%) patients experienced adverse events, mostly diarrhea (n = 19, 38%), nausea (n = 17, 34%) and headache (n = 16, 32%). Conclusion: Apremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.
Authors: P P Vakharia; K A Orrell; D Lee; S M Rangel; E Lund; A E Laumann; D P West; B Nardone Journal: J Eur Acad Dermatol Venereol Date: 2017-04-26 Impact factor: 6.166
Authors: Arthur Kavanaugh; Dafna D Gladman; Christopher J Edwards; Georg Schett; Benoit Guerette; Nikolay Delev; Lichen Teng; Maria Paris; Philip J Mease Journal: Arthritis Res Ther Date: 2019-05-10 Impact factor: 5.156