Efficacy and safety of apremilast for Behçet's syndrome: a real-life single-centre Italian experience.

OBJECTIVES To evaluate the efficacy and safety of apremilast in treating oral ulcers (OUs), the cardinal and high-disabling feature of Behçet's disease (BD). METHODS Twelve consecutive patients affected by BD with recurrent/relapsing OUs resistant and/or intolerant to conventional therapy were enrolled and prospectively followed. The primary endpoint was the number of OUs at week 12. Secondary endpoints were modification from baseline to week 12 in Behçet's Syndrome Activity Score (BSAS), Behçet's Disease Current Activity Form (BDCAF) score, Behçet's Disease Quality of Life (BDQOL) scale and pain of OUs, as measured by a visual analogue scale (VAS). All adverse events (AEs) were recorded during follow-up. Non-parametric tests (Wilcoxon rank test) were used and a P-value <0.05 was considered statistically significant. RESULTS After 12 weeks of apremilast, there was a significant reduction in the number of OUs [0.58 (s.d. 0.67) vs 3.33 (s.d. 1.45) at baseline, P = 0.02] that was paralleled by improvement in disease activity: BSAS was 16.8 (s.d. 9.1) [from 45.9 (s.d. 19.6) at baseline] (P = 0.02), BDCAF score was 0.72 (s.d. 0.65) [vs 2.45 (s.d. 1.0) at baseline] (P = 0.04) and the VAS score for pain decreased to 23.3 (s.d. 13.7) [vs 67.9 (s.d. 17.2) at baseline] (P = 0.02). Consistently, an improvement of BDQOL was assessed (P = 0.02). Clinical improvement led to complete steroid discontinuation in six patients and a tapering of the prednisone dose in two patients (P = 0.016). Colchicine was discontinued in six of nine patients (P = 0.031). AEs related to apremilast occurred in four patients (mainly due to gastrointestinal AEs), leading to drug discontinuation in all of them. CONCLUSION Our preliminary real-world data support the use of apremilast as an effective therapeutic strategy against BD-related recurrent OUs resistant or intolerant to first-line therapy.

[1]  A. Senusi,et al.  The influence of oral health and psycho-social well-being on clinical outcomes in Behçet’s disease , 2018, Rheumatology International.

[2]  D. Kim,et al.  OP0082 Apremilast for behÇet’s syndrome: a phase iii randomised, placebo-controlled, double-blind study (RELIEF) , 2018, WEDNESDAY, 13 JUNE 2018:.

[3]  M. Ralli,et al.  Behçet's disease: New insights into pathophysiology, clinical features and treatment options. , 2018, Autoimmunity reviews.

[4]  R. Moots,et al.  2018 update of the EULAR recommendations for the management of Behçet’s syndrome , 2018, Annals of the rheumatic diseases.

[5]  M. Cutolo,et al.  A Phase III, Randomized, Controlled Trial of Apremilast in Patients with Psoriatic Arthritis: Results of the PALACE 2 Trial , 2016, The Journal of Rheumatology.

[6]  C. Edwards,et al.  Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3) , 2016, Annals of the rheumatic diseases.

[7]  M. Sampaolesi,et al.  Role of Inflammation in Muscle Homeostasis and Myogenesis , 2015, Mediators of inflammation.

[8]  M. Galeazzi,et al.  Mucocutaneous Involvement in Behçet's Disease: How Systemic Treatment Has Changed in the Last Decades and Future Perspectives , 2015, Mediators of inflammation.

[9]  P. Merkel,et al.  Apremilast for Behçet's syndrome--a phase 2, placebo-controlled study. , 2015, The New England journal of medicine.

[10]  A. Glenny,et al.  Interventions for the management of oral ulcers in Behçet's disease. , 2014, The Cochrane database of systematic reviews.

[11]  P. Sfikakis,et al.  Anti-cytokine biologic treatment beyond anti-TNF in Behçet's disease. , 2014, Clinical and experimental rheumatology.

[12]  T. Ergun,et al.  Unmet need in Behcet’s disease: most patients in routine follow-up continue to have oral ulcers , 2014, Clinical Rheumatology.

[13]  D. Gladman,et al.  Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor , 2014, Annals of the rheumatic diseases.

[14]  F. Shahram,et al.  Colchicine versus placebo in Behçet’s disease: randomized, double-blind, controlled crossover trial , 2009, Modern rheumatology.

[15]  G. Almoznino,et al.  Infliximab for the treatment of resistant oral ulcers in Behçet's disease: a case report and review of the literature. , 2007, Clinical and experimental rheumatology.

[16]  Y. Tüzün,et al.  A double-blind trial of colchicine in Behçet's syndrome. , 2001, Arthritis and rheumatism.

[17]  H. Yazıcı,et al.  A double blind study of colchicine in Behçet's disease. , 1980, Haematologica.

[18]  A. Silman,et al.  [Criteria of diagnosis of Behcet's disease]. , 1975, La Tunisie medicale.