OP0028 EFFICACY OF APREMILAST FOR THE PAIN OF ORAL ULCERS ASSOCIATED WITH ACTIVE BEHÇET’S SYNDROME: 12-WEEK RESULTS FROM THE RANDOMIZED, PHASE III RELIEF STUDY
Authors: G. Hatemi, A. Mahr, M. Takeno, D. Kim, M. Melikoglu, S. Cheng, S. Mccue, S. Richter, M. Brunori, M. Paris, M. Chen, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2020)

Background: Oral ulcers (OU) associated with Behçet’s syndrome are often painful, may interfere with the ability to eat and can negatively affect quality of life. 1,2 Apremilast (APR), an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in the treatment of OU associated with Behçet’s syndrome in a phase III, multicenter, randomized, double-blind, placebo (PBO)-controlled study (RELIEF; BCT-002). 3 Objectives: To describe the efficacy of APR treatment in improving OU pain associated with Behçet’s syndrome in RELIEF. Methods: Patients were randomized (1:1) to APR 30 mg twice daily (APR 30 BID) or PBO twice daily for a 12-week PBO-controlled phase, followed by a 52-week active treatment extension. Eligible patients were ≥18 years of age and had active Behçet’s syndrome with ≥3 OU at randomization or ≥2 OU at screening and randomization and without active major organ involvement. Clinical improvement in OU was evaluated by the area under the curve for the number of OU through Week 12 (AUC Wk0-12 ; primary efficacy endpoint) and by assessments of OU number. Patient-reported OU pain was evaluated by the 100-mm visual analogue scale (VAS). The statistical tests were 2-sided (α=0.05). The proportions of patients achieving the minimal clinically important difference (MCID) and higher rates of improvement, defined as ≥10-mm, 4 ≥30-mm (3-fold MCID), ≥50-mm (5-fold MCID) improvements in OU pain VAS scores, respectively, were analyzed through Week 12. An ANCOVA model was used to analyze the primary endpoint and assessments of OU number and OU pain (VAS). The proportion of patients achieving improvement in OU pain VAS scores at Week 12 were summarized descriptively. Results: A total of 207 patients were randomized and received ≥1 dose of study medication (APR: n=104; PBO: n=103). At baseline, the mean (SD) number of OU was 4.2 (3.7) in the APR 30 BID group and 3.9 (2.7) in the PBO group, and the mean (SD) OU pain VAS scores were 61.2 (27.6) and 60.8 (26.9), respectively. At Week 12, significantly greater improvements were observed with APR 30 BID vs. PBO in AUC Wk0-12 (least-squares [LS] mean [SE]: 129.5 [15.9] vs. 222.1 [15.9]; P &lt;0.0001), number of OU (LS mean [SE]: 1.1 [0.2] vs. 2.0 [0.3]; P =0.0003) and OU pain VAS scores (LS mean [SE] change from baseline: −40.7 [3.3] vs. −15.9 [3.3]; P &lt;0.0001). The proportion of patients who achieved the MCID of ≥10-mm improvement in OU pain VAS scores at Week 12 was greater with APR 30 BID vs. PBO; this pattern was also observed for the higher 3- and 5-fold improvements in MCID (Figure 1). Greater proportions of APR 30 BID vs. PBO patients achieved ≥10-mm and ≥30-mm improvements in OU pain VAS scores over 12 weeks. Notably, greater achievement of ≥50-mm improvement in OU pain VAS scores was observed with APR 30 BID vs. PBO as early as Week 1 and maintained up to Week 12 (Figure 2). Conclusion: For patients with active Behçet’s syndrome, APR 30 BID provided significantly greater improvements vs. PBO in OU number and OU pain at Week 12, including the greater proportion of patients achieving MCID and 3- and 5-fold MCID of OU pain in the APR 30 BID group vs. the PBO group. These results indicate a clinically meaningful treatment effect of APR 30 BID on the OU associated with Behçet’s syndrome. References: [1]Kokturk A. Patholog Res Int . 2012;2012:690390. [2]Hatemi G, et al. Ann Rheum Dis . 2008;67:1656-1662. [3]Hatemi G, et al. N Engl J Med . 2019;381:1918-1928. 4. Dworkin RH, et al. J Pain . 2008;9:105-121. Disclosure of Interests: Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker, Alfred Mahr Consultant of: Celgene, Speakers bureau: Roche, Chugai, Mitsuhiro Takeno Speakers bureau: Esai, Tanabe-Mitsubishi – speaker; Celgene Corporation – advisory board, Doyoung Kim: None declared, Melike Melikoglu: None declared, Sue Cheng Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Shannon McCue Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Sven Richter Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Michele Brunori Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Maria Paris Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of study conduct, Mindy Chen Employee of: Amgen Inc. – employment; Celgene Corporation – employment at the time of the conduct, Yusuf Yazici Consultant of: BMS, Celgene Corporation, Genentech, Sanofi – consultant, Consultant of: BMS, Celgene Corporation, Genentech, Sanofi – consultant