Apremilast in Refractory Behçet’s Syndrome: A Multicenter Observational Study

Frontiers in Immunology

Stéphane Barete²  Laurent Misery³  Olivier Fain⁴  Delphine Gobert⁴  Karim Sacre⁵  Tiphaine Goulenok⁵  Laurence Bouillet⁷  Estibaliz Lazaro⁸  Pascal Sève⁹  Mathieu Gerfaud-Valentin⁹  Yvan Jamilloux⁹  Matheus Vieira^1,11  Patrice Cacoub^1,11  Cloé Comarmond^1,11  David Saadoun^1,11  Mathieu Vautier^1,11  Alexandre Le Joncour^1,11  Solène Buffier^1,11 

[1]0INSERM, UMR_S 959, Paris, France

[2]1UF de Dermatologie, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France

[3]2Department of Dermatology, Brest University Hospital, Brest, France Univ Brest, Brest, France

[4]3Service de Médecine Interne et Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Faculté de Médecine Sorbonne Université, Hôpital Saint Antoine, Sorbonne Universités AP-HP, Paris, France

[5]4Département 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

[6]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

[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]Department of Internal Medicine, Hopital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France

[10]Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DHU i2B), Sorbonne Universités, UPMC Université Paris 06, UMR 7211, Paris, France

[11]INSERM 959, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France

[12]Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France

[13]Service de Médecine Interne, CHUGA, Unité Inserm 1036, Université Grenoble Alpes (UGA), Grenoble, France

[14]Sorbonne Universités AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, Paris, France

关键词: Behçet;    apremilast;    efficacy;    safety;    joint;    skin;   

DOI  :  10.3389/fimmu.2020.626792

来源: DOAJ

【 摘 要 】

ObjectiveMucocutaneous 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.MethodsFrench 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.ResultsAt 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%).ConclusionApremilast seems effective in BS-related articular disease refractory to colchicine and DMARDs. Discontinuation rates were significantly higher than that reported in clinical trials.

【 授权许可】

Unknown