OP0146\u2005EFFICACY OF APREMILAST FOR ORAL ULCERS ASSOCIATED WITH ACTIVE BEHÇET’S SYNDROME OVER 64 WEEKS: RESULTS FROM A PHASE III STUDY

Abstract

Background Behçet’s syndrome is a chronic, relapsing, multi-system inflammatory disorder characterized by recurrent oral ulcers (OU) that can impact quality of life (QoL). Objectives To assess apremilast (APR) efficacy and safety for the treatment of OU associated with Behçet’s syndrome in the phase III RELIEF study for up to 64 wks and at 4-wk follow-up (after APR discontinuation). Methods Adult patients (pts) with active Behçet’s syndrome (defined by ≥3 OU at randomization or ≥2 OU at screening and at randomization without active major organ involvement) were randomized (1:1) to placebo (PBO) or APR 30 mg twice daily for 12 wks. All pts then received APR through Wk 64. Pts who completed the Wk 64 visit or discontinued treatment at any time and for any reason in the study entered a 4-wk posttreatment observational follow-up. The primary endpoint was area under the curve for the number of OU over 12 wks (AUCWk0-12), which reflects the number of OU over time and accounts for the recurring-remitting course of OU. Other outcomes included change from baseline in OU pain VAS, complete response (% of pts with no OU) or partial response (% of pts with ≥50% reduction in number of OU), disease activity (Behçet’s Disease Current Activity Form [BDCAF], composed of the Behçet’s Disease Current Activity Index [BDCAI], Pt’s and Clinician’s Perception of Disease Activity and Behçet’s Syndrome Activity Score [BSAS]), and QoL (Behçet’s Disease QoL [BDQoL]). Results A total of 207 pts were randomized and received ≥1 dose of study medication (PBO: n=103; APR: n=104); 178 pts entered the active treatment phase (PBO/APR: n=83; APR: n=95) and 143 pts (PBO/APR: n=68; APR: n=75) completed Wk 64. The primary endpoint of AUCWk0-12 was achieved; significantly lower AUCWk0-12 was observed for APR vs PBO (P<0.0001). Significantly lower OU counts (P≤0.0015) and OU pain (P≤0.0035) were observed with APR vs PBO from Wks 1 through 12; APR efficacy was sustained up to 64 wks (Figure). Significantly greater improvements with APR were observed in complete and partial response of OU at Wk 12 (P<0.0001); effects were maintained through Wk 64 (53.3% and 76.0%, respectively). Pts initially randomized to PBO and switched to APR at Wk 12 showed comparable benefits through Wk 64 (Figure). Improvements in disease activity (BDCAI: P=0.0335; BSAS: P<0.0001) and QoL (BDQoL: P=0.0003) were significant in pts receiving APR vs PBO at Wk 12 and maintained at Wk 64. Comparable effects in pts who switched from PBO to APR were observed at Wk 64. After APR was discontinued before or at Wk 64, the improvements in OU assessments decreased within 4 wks. Disease activity measures and BDQoL similarly indicated recurrence of symptoms at the 4-wk follow-up. Incidence of any adverse event (AE) was comparable for pts initially randomized to APR vs PBO during the PBO-controlled period (78.8% vs 71.8%) and through Wk 64 for pts who continued APR vs pts who switched from PBO to APR (84.3% vs 86.5%). The most common AEs with APR were diarrhea, nausea, headache and upper respiratory tract infection; most AEs were mild/moderate in severity, and no new safety concerns were identified. Conclusion APR demonstrated efficacy in the treatment of OU in pts with active Behçet’s syndrome. Benefits were sustained for up to 64 wks with continued treatment. APR was well tolerated, and safety was consistent with the known safety profile of APR. Disclosure of Interests Gulen Hatemi Consultant for: Abbvie, Amgen, BMS, Janssen, MSD, Pfizer, UCB, Speakers bureau: Abbvie, Amgen, BMS, Jansen, MSD, Pfizer, UCB, Alfred Mahr Consultant for: Chugai Pharma France, Speakers bureau: Roche SAS Chugai Pharma France, Mitsuhiro Takeno Consultant for: Celgene Corporation, Doyoung Kim: None declared, David Saadoun Grant/research support from: Roche, Abbvie, Consultant for: Janssen, Celgene, Abbvie, Roche, Haner Direskeneli: None declared, Sue Cheng Employee of: Celgene Corporation, Shannon McCue Employee of: Celgene Corporation, Maria Paris Employee of: Celgene Corporation, Mindy Chen Employee of: Celgene Corporation, Yusuf Yazici Shareholder of: Samumed, LLC, Consultant for: Celgene Corporation, BMS, Genentech, Sanofi, Employee of: Samumed, LLC