Dupilumab With Concomitant Topical Corticosteroids in Atopic Dermatitis Patients Who Are Inadequately Controlled With or Medically Inadvisable for Cyclosporine A: a Phase 3 Clinical Trial (LIBERTY AD CAFÉ) Presented at the 2017 Fall Clinical Dermatology Conference; Las Vegas, NV, USA; October 12-15, 2017. Marjolein de Bruin-Weller1, Diamant Thaçi2, Catherine Smith3, Allen Radin4, Rick Zhang5, Bolanle Akinlade4, Abhijit Gadkari4, Laurent Eckert6, Thomas Hultsch7, Gianluca Pirozzi8, Neil MH Graham4, Brad Shumel4 1University Medical Center Utrecht, Utrecht, Netherlands; 2University of Lübeck, Lübeck, Germany; 3St. John’s Institute of Dermatology, London, UK; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 5Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA; 6Sanofi, Chilly-Mazarin, France; 7Sanofi, Cambridge, MA, USA; 8Sanofi, Bridgewater, NJ, USA B A C K G R O U N D 1 α O B J E C T I V E C O N C L U S I O N S – – M E T H O D S Study design Patient eligibility – � � � � � Safety Table 1. Baseline characteristics. – – – – – – – – � � � Outcomes – – – – – R E S U LT S Patient disposition and baseline characteristics Efficacy P – Placebo SC qw+TCSb (n = 108) Dupilumab 300 mg SC qw+TCSb (n = 110) Post-treatment options Open-label extension Safety follow-up through Week 28 Screening (2 weeks) and TCS standardization (2 weeks) Dupilumab 300 mg SC q2w+TCSb (n = 107) Treatment period (16 weeks) Follow-up period (12 weeks) Loading dose (Day 1a) Day –28 to Day –1 Baseline Week 28Week 16 R Figure 1. Study design. 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 P ro p o rt io n o f p a ti e n ts a c h ie vi n g E A S I- 75 f ro m b a se lin e ( % ) Weeks Overall population (primary endpoint) 29.6 62.6* 59.1* *P < 0.0001 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 Weeks Patients with prior CsA usea Placebo+TCS Dupilumab 300 mg q2w+TCS *P = 0.0001 †P = 0.0002 26.4 58.0* 56.5† (A) (B) Dupilumab 300 mg qw+TCS Figure 2. Proportion of patients of the overall study population (A) and patients with prior CsA use (B) achieving EASI-75 at Week 16 (primary endpoint). 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 P ro p o rt io n o f p a ti e n ts w it h ≥ 4 -p o in t im p ro ve m e n t I D L Q I fr o m b a se lin e ( % ) Weeks POEM (MCID ≥ 4) DLQI (MCID ≥ 4) 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 P ro p o rt io n o f p a ti e n ts w it h ≥ 4 -p o in t im p ro ve m e n t in P O E M f ro m b a se lin e ( % ) Weeks 84.0* 42.1 87.6* 44.2 *P < 0.0001 77.1* 77.8* *P < 0.0001 (A) (B) Placebo+TCS Dupilumab 300 mg q2w+TCS Dupilumab 300 mg qw+TCS Figure 5. Proportion of patients achieving a ≥ 4-point improvement in POEMa (A) and DLQIb (B) from baseline to Week 16. 28.0 64.1* 55.3† 0 10 20 30 40 50 60 70 80 90 100 P ro p o rt io n o f p a ti e n ts r e p o rt in g n o p a in /d is c o m fo rt a t W e e k 1 6 (% ) *P < 0.0001 †P = 0.0004 Placebo+TCS Dupilumab 300 mg q2w+TCS Dupilumab 300 mg qw+TCS 22/60 26/5635/56 Figure 6. Proportions of patients reporting “no pain/discomfort” on the EQ-5D pain/discomfort subscale at Week 16.a 29.6 18.6 62.6* 52.4† 59.1* 50.0 ‡ 0 10 20 30 40 50 60 70 80 90 100 CAFÉ CHRONOS CAFÉ-like P a ti e n ts a c h ie vi n g E A S I- 75 ( % ) EASI-75: Similar in CAFÉ (Week 16) and CHRONOS CAFÉ-like populations (Week 52) *P < 0.0001 †P = 0.0048 ‡P = 0.0008 32/ 108 23/ 46 11/ 21 11/ 59 67/ 107 65/ 110 Placebo+TCS Dupilumab 300 mg q2w+TCS Dupilumab 300 mg qw+TCS Figure 7. Comparison of CAFÉ and subgroup analysis of CAFE-like patients in CHRONOS. 0 2 4 6 8 10 12 14 16 L S m e a n p e rc e n t c h a n g e in S C O R A D sc o re f ro m b a se lin e ( M I) Weeks –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 0 2 4 6 8 10 12 14 16 L S m e a n p e rc e n t c h a n g e in E A S I sc o re f ro m b a se lin e ( M I) Weeks *P < 0.0001 –46.6 –79.8* –79.8* –78.2* Placebo+TCS Dupilumab 300 mg q2w+TCS Dupilumab 300 mg qw+TCS –29.5 –62.4* –62.4* –58.3* EASI * P < 0.0001 SCORAD(A) (B) Figure 3. Least squares mean percent change in EASI (A) and SCORAD score (B) from baseline to Week 16. –100 –90 –80 –70 –60 –50 –40 –30 –20 –10 0 0 2 4 6 8 10 12 14 16 Weeks –25.4–25.4 –53.9‡–53.9‡ –51.7‡–51.7‡ *P = 0.0214 †P = 0.0017 ‡P < 0.0001 * † L S m e a n p e rc e n ta g e c h a n g e in w e e k ly a ve ra g e o f p e a k p ru ri tu s N R S f ro m b a se lin e ( M I) Placebo+TCS Dupilumab 300 mg q2w+TCS Dupilumab 300 mg qw+TCS Figure 4. Least squares mean percent change in weekly average of peak daily pruritus NRS from baseline at Week 2 and Week 16. Table 2. Overall summary of number of patients with AEs through the 16-week treatment period – SAF. References Acknowledgments Disclosures FC17PosterRegeneronSanofideBruin-WellerDupilumabWithConcomitantTopical.pdf