Efficacy and Safety of Apremilast for Behçet's Syndrome

A Real-Life Single-Centre Italian Experience

Giacomo De Luca; Adriana Cariddi; Corrado Campochiaro; Daniele Vanni; Nicola Boffini; Alessandro Tomelleri; Giulio Cavalli; Lorenzo Dagna


Rheumatology. 2020;59(1):171-175. 

In This Article

Abstract and Introduction


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.


Behçet's disease (BD) is a chronic relapsing inflammatory disorder characterized by recurrent oral (OUs) and genital ulcers (GUs), skin lesions, ocular manifestations (e.g. uveitis, conjunctivitis), arthritis and other systemic involvement as gastrointestinal, neurologic and vascular disease.[1] Mucocutaneous lesions are the hallmark of BD: multiple OUs occur in almost all patients, while GUs occur in 60–65% of cases; diverse skin lesions overall occur in 70–75% of cases and may include erythema nodosum, pseudofolliculitis, papulopustular lesions and acneiform nodules.[1] Mucocutaneous BD with recurrent OUs is highly disabling and can significantly affect patients' quality of life (QOL).[1–3]

The EULAR recommendation for the mucocutaneous lesions of BD includes colchicine and topical or systemic glucocorticoids as first-line therapy.[4] However, a substantial proportion of patients fail to respond to these therapies and are currently treated with various conventional or biologic immunosuppressive agents, often with unsatisfactory results.[5–10] Effective strategies for refractory OUs are needed to alleviate the burden of BD.

Apremilast is an oral phosphodiesterase-4 inhibitor approved for moderate to severe skin psoriasis and PsA.[11–13] Based on favourable results in phase II[14] and III trials[15] (ClinicalTrials.gov identifier: NCT02307513), apremilast is emerging as a promising therapeutic option for mucocutaneous BD.[4] However, the clinical effectiveness of apremilast in the real-life management of difficult-to-treat BD patients remains to be determined.

Here we report the encouraging results of a prospective study evaluating the efficacy and safety of apremilast in a cohort of BD patients with recurrent/relapsing OUs that were refractory and/or intolerant to conventional therapies.