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

Abstract

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.

Efficacy and safety of apremilast and its impact on serum cytokine levels in patients with Behçet's disease

“…The long‐term efficacy of apremilast has been reported for oral ulcers for up to 64 weeks 23 and for skin and articular symptoms for up to 6 months 22,24–26 . However, similar to the present report, there have been reports of only skin lesions or arthritis flare‐ups during apremilast treatment, 20,24 and the effect on oral ulcers may not match the effect on skin or arthritis.…”

Recent Insights into the Management of Behçet Syndrome

“…Among 30 patients who had refractory joint involvement, 65% had complete response and 17% had partial response at month 6. 71 Apremilast was generally well tolerated, the main AEs being related to the gastrointestinal system.…”

Effectiveness of apremilast against Behçet's disease-associated mucocutaneous and joint involvement confirmed through switching from adalimumab

“…The first meta-analysis on the effectiveness of apremilast for involvement other than BD-associated OU by Iizuka et al showed that apremilast significantly improved GU, EN, pseudofolliculitis, and arthritis within 12 weeks from the initiation of administration (4). The meta-analysis included studies targeting patients with mucocutaneous and joint involvement who were resistant to colchicine, systemic glucocorticoids, and immunosuppressive agents (2,(5)(6)(7)(8)(9). Most of the studies included patients who were refractory to treatment with tumour necrosis factor (TNF) inhibitors (up to 76.9%), with different percentages in each study (5)(6)(7)(8)(9).…”

“…The meta-analysis included studies targeting patients with mucocutaneous and joint involvement who were resistant to colchicine, systemic glucocorticoids, and immunosuppressive agents (2,(5)(6)(7)(8)(9). Most of the studies included patients who were refractory to treatment with tumour necrosis factor (TNF) inhibitors (up to 76.9%), with different percentages in each study (5)(6)(7)(8)(9). Apremilast inhibits the production of TNF and other inflammatory cytokines and promotes the production of the anti-inflammatory cytokine interleukin-10 (1, 2, 9).…”