POS0828 CONSISTENT EFFICACY WITH APREMILAST IN MEN AND WOMEN TO TREAT ORAL ULCERS ASSOCIATED WITH BEHÇET’S SYNDROME: PHASE 3 RELIEF STUDY RESULTS
Authors: G. Hatemi, A. Mahr, M. Takeno, D. Kim, M. Melikoglu, S. Cheng, S. Richter, S. Jardon, M. Paris, M. Chen, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2021)

Background: Painful, recurring oral ulcers (OU) associated with Behçet’s syndrome negatively affect quality of life (QoL). Differences across sexes were reported in the frequency of disease manifestations, disease course, and response to colchicine. The phase 3, randomized, double-blind, placebo (PBO)-controlled RELIEF study showed overall efficacy of apremilast (APR) for OU associated with Behçet’s syndrome, including improvements in OU pain, disease activity, and QoL. Objectives: To evaluate the consistency of efficacy with APR in men and women with Behçet’s syndrome. Methods: Adults with active Behçet’s syndrome and ≥3 OU at randomization or ≥2 OU at screening and randomization, without active major organ involvement, were randomized to APR 30 mg BID or PBO during the 12-wk PBO-controlled phase. Randomization was stratified by sex. The primary endpoint was area under the curve for the number of OU through Wk 12 (AUC Wk0-12 ) to assess continued efficacy over the time period in a symptom that waxed and waned. Key secondary endpoints included OU pain, complete response (OU-free), maintenance of complete response, and QoL at Wk 12. Disease activity was also assessed using Behçet’s Syndrome Activity Score (BSAS) and Behçet’s Disease Current Activity Index Form (BDCAF). QoL was assessed using Behçet’s Disease QoL (BDQoL). Prespecified subgroup analyses in men and women were performed to assess treatment effect in primary and secondary endpoints. Results: Eighty men and 127 women were randomized and received ≥1 dose of study medication. Mean age was 38.7 yrs (men) and 40.8 yrs (women). Mean (SD) OU count at baseline was 3.4 (1.4) (PBO) and 3.7 (1.5) (APR) for men and 4.3 (3.2) (PBO) and 4.5 (4.5) (APR) for women. Greater improvements in favor of APR vs PBO were observed in AUC Wk0-12 in men and women (Figure 1). Consistency in efficacy with APR was observed between men and women, with greater reduction in pain and achievement of OU complete response (OU-free) and maintenance of response at Wk 12 vs PBO (Table 1). In men and women, consistent treatment effects in favor of APR vs PBO were observed for disease activity and QoL measures, although moderate treatment differences were observed in BDCAI (men/women) and BDQoL (men) (Table 1). Conclusion: Consistent treatment effects in favor of APR vs PBO in clinically relevant outcomes, including OU number and pain, OU complete response, and disease activity measures, were observed in men and women with OU associated with Behçet’s syndrome. Key Secondary Efficacy Outcomes at Wk 12 Men Women PBO (n = 40 ) APR (n = 40 ) Tx Difference [95% CI] PBO (n = 63 ) APR (n = 64 ) Tx Difference [95% CI] OU CR, n/N (%) 8/40 (20.0) 21/40 (52.5) 32.6 [12.8, 52.4] 15/63 (23.8) 34/64 (53.1) 29.3 [13.2, 45.4] OU CR 6 + 6*, n/N (%) 1/40 (2.5) 10/40 (25.0) 22.8 [8.8, 36.8] 4/63 (6.3) 21/64 (32.8) 26.5 [13.6, 39.3] Pain (VAS)† -12.0 (4.8) -37.6 (4.9) -25.6 [-37.2, -14.1] -17.4 (4.4) -41.5 (4.3) -24.1 [-34.9, -13.3] BSAS† -1.3 (2.4) -14.4 (2.4) -13.1 [-18.8, -7.3] -7.7 (2.4) -19.7 (2.4) -12.0 [-18.0, -6.0] BDCAF† BDCAI -0.1 (0.3) -0.5 (0.3) -0.4 [-1.1, 0.4] -0.7 (0.3) -1.3 (0.3) -0.6 [-1.2, 0.0] Patient’s Perception of Disease Activity -0.2 (0.3) -1.4 (0.3) -1.2 [-1.9, -0.5] -1.0 (0.2) -1.8 (0.2) -0.9 [-1.4, -0.3] Clinician’s Overall Perception of Disease Activity -0.2 (0.3) -1.5 (0.3) -1.3 [-1.9, -0.7] -1.0 (0.2) -1.7 (0.2) -0.7 [-1.3, -0.2] BDQoL† -0.7 (1.0) -2.2 (1.0) -1.5 [-3.8, 0.8] -0.3 (0.9) -4.4 (0.9) -4.1 [-6.3, -2.0] LOCF analyses. *Proportion of patients achieving an OU CR by Wk 6, and remaining OU-free for ≥6 additional wks during the 12-wk PBO-controlled treatment phase. †LS mean (SE) change from baseline. BSAS = Behçet’s Syndrome Activity Scores; BDCAF = Behçet’s Disease Activity Form; CR = complete response; n = number of patients randomized to treatment; Tx = treatment. Acknowledgements: This study was funded by Celgene. Additional analyses were funded by Amgen Inc. Writing support was funded by Amgen Inc. and provided by Kristin Carlin, RPh, MBA, of Peloton Advantage, LLC, an OPEN Health company. Disclosure of Interests: Gulen Hatemi Speakers bureau: AbbVie, Novartis, and UCB, Grant/research support from: Celgene, Alfred Mahr Speakers bureau: Chugai and Roche, Consultant of: Celgene and Chugai, Mitsuhiro Takeno Speakers bureau: AbbVie, Esai, and Mitsubishi-Tanabe, Consultant of: Celgene, Grant/research support from: Novartis, Doyoung Kim: None declared, Melike Melikoglu: None declared, Sue Cheng Employee of: Amgen Inc., Sven Richter Employee of: Amgen Inc., Shauna Jardon Employee of: Amgen Inc., Maria Paris Employee of: Amgen Inc., Mindy Chen Employee of: Amgen Inc., Yusuf Yazici Consultant of: Bristol-Myers Squibb, Celgene, Genentech, and Sanofi