S2010517 FCPANP 2020 Silverberg_without QR code.indd Presented at the 5th Fall Clinical Dermatology Conference for PAs & NPs (FCPANP). BACKGROUND • The Patient-Oriented Eczema Measure (POEM) is a validated, 7-item questionnaire, which assesses patient-reported frequency of atopic dermatitis (AD) symptoms from the previous week1–3 – The Harmonising Outcome Measures for Eczema initiative recommends POEM as the core outcome instrument for measuring patient-reported AD symptoms in clinical trials4 • Dupilumab is a fully human monoclonal antibody5,6 that blocks the shared receptor component for interleukin (IL)-4 and IL-13, thus inhibiting signaling of both IL-4 and IL-13, which are key and central drivers of type 2 infl ammation in multiple diseases7 • In the 52-week, phase 3, randomized, double-blinded LIBERTY AD CHRONOS trial (NCT02260986), dupilumab with concomitant topical corticosteroids (TCS) vs placebo with TCS signifi cantly improved AD signs, symptoms, and patient quality of life with an acceptable safety profi le8 Long-Term Effect of Dupilumab With Concomitant Topical Corticosteroids on POEM in Adults With Moderate-to-Severe Atopic Dermatitis: LIBERTY AD CHRONOS Trial Jonathan I. Silverberg1 , Benjamin Lockshin2, Melinda Gooderham3,4, Zhen Chen5, Abhijit Gadkari5, Ana B. Rossi6 1George Washington University School of Medicine, Washington, DC, USA; 2Georgetown University, Rockville, MD, USA; 3SKiN Centre for Dermatology, Peterborough, ON, Canada; 4Queen’s University, Kingston, ON, Canada; 5Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 6Sanofi Genzyme, Cambridge, MA, USA METHODS Study design • The detailed study design, patient population, effi cacy, and safety of the CHRONOS study have been previously reported8 Endpoints • Outcomes assessed in this analysis included – Least squares (LS) mean change from baseline to Week 52 in total POEM score – Proportion of patients in severity grades classifi ed according to POEM scores through Week 52 – Proportion of patients in each category of the 7 items of POEM through Week 52 0 = No days 1 = 1–2 days 2 = 3–4 days 3 = 5–6 days 4 = Every day Analysis • The analysis presented here is focused on the placebo + TCS group (control) and the dupilumab 300 mg q2w + TCS group (approved dose in adults) • Effi cacy was analyzed in all randomized patients (full analysis set) • Safety was analyzed in the safety analysis set, which included all patients who received ≥ 1 dose of study drug OBJECTIVE • To analyze the effect of dupilumab with concomitant TCS on POEM in a 52-week, phase 3 trial in adults with moderate-to-severe AD using data from the LIBERTY AD CHRONOS trial Screening Moderate-to-severe AD for ≥ 3 years Age: ≥ 18 years IGA: ≥ 3 EASI: ≥ 16 BSA: ≥ 10% Post-treatment options: • Open-label extension • Safety follow-up through Week 64 Treatment period (52 weeks) Follow-up period (12 weeks)Loading dose on (Day 1a ) Day –35 to –1 Baseline Week 64Week 52 R 3 3 1 Dupilumab 300 mg SC qw + TCSb (n = 319) Dupilumab 300 mg SC q2w + TCSb (n = 106) Placebo SC qw + TCSb (n = 315) Figure 1. CHRONOS study design. aDupilumab, 600 mg loading dose; placebo, matching placebo. bPatients were required to use TCS for the entire treatment period. BSA, body surface area; IGA, Investigator’s Global Assessment; EASI, Eczema Area and Severity Index; R, randomization; qw, weekly; q2w, every 2 weeks; SC, subcutaneous. 0 –28 Placebo qw + TCS Dupilumab 300 mg q2w + TCS 299/16 102/4 W1 W2 W4 W6 W8 W12 W16 W20 W24 W28 W32 W36 W40 W44 W48 W52 297/18 101/5 272/43 99/7 249/66 98/8 241/74 94/12 212/103 93/13 189/126 92/14 174/141 90/16 160/155 88/18 152/163 87/19 145/170 85/21 136/179 84/22 128/187 84/22 125/190 82/24 123/192 84/22 121/194 84/22 0 4 8 Week 12 16 20 24 28 32 36 40 44 48 52 –24 –20 –16 L S m e a n ( ± S E ) c h a n g e in t o ta l P O E M –12 –8 –13.7************ *************** ************ *** *** ** –5.9 –4 Placebo qw + TCS (n = 315) Dupilumab 300 mg q2w + TCS (n = 106) Number of patients/ Imputed subjects Figure 2. Change in total POEM score from baseline up to Week 52. **P < 0.01, ***P < 0.0001 vs placebo. SE, standard error P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 56.8 40.6 2.5 Baseline Week 2 Week 4 Week 8 Mild (0–7) Moderate (8–19) Severe (20–28) % of patients in POEM Category Week 16 Week 52A 33.0 54.6 12.4 35.9 46.7 17.5 41.9 40.6 17.5 51.4 30.8 17.8 68.6 18.1 13.3 B P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 61.3 36.8 1.9 Baseline Week 2 Week 4 Week 8 Week 16 Week 52 17.0 61.3 21.7 11.3 50.0 38.7 16.0 33.0 50.9 17.0 34.0 49.1 23.6 16.0 60.4 Figure 3. Categorical change in AD severity according to total POEM score in (A) placebo + TCS group and (B) dupilumab 300 mg q2w group. Missing POEM scores were imputed into “Severe” category. P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 88.9 5.7 4.4 Baseline Week 2 Week 4 Week 8 Placebo qw + TCSA Itchy Skin Disturbed Sleep Bleeding Skin Weeping/Oozing Skin Cracked Skin Flaking Skin Dry/Rough Skin B C D E F G 0 days 1–2 days 3–4 days 5–6 days Every day% of patients in POEM category Week 16 Week 52 66.0 14.6 9.5 7.9 1.9 65.4 8.6 13.0 11.1 1.9 66.3 9.2 10.8 11.4 2.2 71.4 7.9 9.2 9.5 1.9 78.7 4.1 6.0 6.7 4.4 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 93.4 3.8 1.9 Baseline Week 2 Week 4 Week 8 Dupilumab 300 mg q2w + TCS Week 16 Week 52 55.7 10.4 17.9 15.1 40.6 14.2 17.0 23.6 4.7 39.6 7.5 11.3 34.0 7.5 36.8 7.5 15.1 27.4 13.2 34.0 1.9 17.0 30.2 17.0 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 31.1 14.9 17.1 20.3 16.5 Baseline Week 2 Week 4 Week 8 Placebo qw + TCS Week 16 Week 52 19.4 7.6 15.6 26.3 31.1 21.6 5.1 12.1 24.8 36.5 30.2 5.1 9.8 20.3 34.6 44.8 4.4 7.3 14.3 29.2 63.8 1.3 3.5 9.2 22.2 Dupilumab 300 mg q2w + TCS P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 30.2 20.8 17.9 19.8 11.3 Baseline Week 2 Week 4 Week 8 Week 16 Week 52 9.4 8.5 14.2 34.0 34.0 7.5 6.6 8.5 24.5 52.8 12.3 4.7 1.9 17.9 63.2 15.1 2.8 4.7 13.2 64.2 20.8 1.9 1.9 9.4 66.0 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Placebo qw + TCS Week 16 Week 52 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Week 16 Week 52 30.8 12.7 21.3 21.6 13.7 19.0 18.1 9.2 25.1 28.6 25.4 7.0 16.2 22.5 28.9 32.7 8.3 10.5 23.5 25.1 47.6 5.7 10.5 15.9 20.3 64.4 4.1 2.9 10.5 18.1 23.6 22.6 15.1 28.3 10.4 8.5 13.2 5.7 23.6 49.1 7.5 8.5 19.8 63.2 11.3 2.8 3.8 17.0 65.1 13.2 3.8 1.9 20.8 60.4 21.7 1.9 13.2 63.2 Dupilumab 300 mg q2w + TCS P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Week 16 Week 52 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Week 16 Week 52 22.5 10.2 19.7 23.5 24.1 14.6 14.3 7.6 24.1 39.4 23.2 6.0 11.1 19.7 40.0 31.4 5.4 6.7 19.0 37.5 45.1 3.5 9.8 13.7 27.9 63.8 1.64.1 8.3 22.2 26.4 11.3 11.3 29.2 21.7 7.5 12.3 2.8 18.9 58.5 8.5 6.6 1.9 16.0 67.0 12.3 2.8 1.9 13.2 69.8 15.1 1.9 17.0 65.1 21.7 2.8 12.3 62.3 Placebo qw + TCS Dupilumab 300 mg q2w + TCS 21.7 20.8 17.9 6.6 33.0 51.9 16.0 15.1 11.3 5.7 11.3 9.4 12.3 35.8 31.1 18.9 15.1 6.6 12.3 47.2 19.8 1.9 45.3 25.5 7.5 8.5 23.6 4.7 47.2 16.0 35.2 11.1 15.2 22.2 16.2 53.7 13.0 14.0 11.4 7.9 36.2 11.1 18.4 21.9 12.4 43.5 9.2 14.6 21.0 11.7 55.6 7.6 15.9 11.4 9.5 70.5 4.4 4.4 12.7 7.9 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Placebo qw + TCS Week 16 Week 52 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Dupilumab 300 mg q2w + TCS Week 16 Week 52 32.1 12.3 16.0 26.4 13.2 63.2 13.2 8.5 6.6 8.5 22.6 9.4 28.3 23.6 16.0 10.4 22.6 12.3 35.8 18.9 30.2 1.9 35.8 20.8 11.3 5.7 25.5 23.6 36.8 8.5 46.7 10.5 9.5 17.1 16.2 64.4 11.7 6.3 12.7 46.0 9.5 11.7 17.5 15.2 50.5 9.2 11.4 18.4 10.5 58.4 8.3 8.6 14.6 10.2 73.7 6.3 8.3 8.6 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Placebo qw + TCS Week 16 Week 52 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Dupilumab 300 mg q2w + TCS Week 16 Week 52 3.2 4.8 50.0 13.2 3.8 18.9 14.2 85.8 6.6 34.0 10.4 15.1 18.9 21.7 9.4 31.1 17.0 16.0 26.4 32.1 6.6 26.4 18.9 16.0 7.5 31.1 20.8 27.4 13.2 61.3 13.7 4.4 8.3 12.4 85.1 5.7 6.3 59.4 12.4 4.1 9.8 14.3 60.0 12.4 3.8 12.4 11.4 67.3 9.5 4.1 10.8 8.3 80.0 4.4 6.0 6.7P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Placebo qw + TCS Week 16 Week 52 P ro p o rt io n o f p a ti e n ts ( % ) 100 80 60 40 20 0 Baseline Week 2 Week 4 Week 8 Dupilumab 300 mg q2w + TCS Week 16 Week 52 2.9 2.2 2.8 3.8 Figure 4. Categorical change in each response on the individual questions of the POEM questionnaire (A) itchy skin, (B) disturbed sleep, (C) bleeding skin, (D) weeping/oozing skin, (E) cracked skin, (F) fl aking skin, and (G) dry/rough skin. Missing POEM scores were imputed into “Every day” category. Table 1. Baseline demographics and disease characteristics (full analysis set). Scoring Placebo qw + TCS (n = 315) Dupilumab 300 mg q2w + TCS (n = 106) Age, mean (SD), years – 36.6 (13.01) 39.6 (13.98) Male, n (%) – 193 (61.30) 62 (58.50) Total POEM, mean (SD) 0–28 20.0 (5.99) 20.3 (5.68) Itchy skin 0–4 3.8 (0.54) 3.9 (0.43) Sleep disturbance 0–4 2.2 (1.48) 2.4 (1.39) Bleeding skin 0–4 2.2 (1.44) 2.2 (1.36) Weeping/oozing skin 0–4 1.8 (1.47) 1.9 (1.53) Cracked skin 0–4 2.9 (1.36) 3.0 (1.28) Flaking skin 0–4 3.2 (1.18) 3.2 (1.32) Dry/rough skin 0–4 3.7 (0.73) 3.7 (0.75) AD severity according to POEM, n (%) Mild 0–7 8 (2.5) 2 (1.9) Moderate 8–19 128 (40.6) 39 (36.8) Severe 20–28 178 (56.8) 65 (61.3) SD, standard deviation. Table 2. Overall safety summary of patients during the 52-week treatment period (safety analysis set). Patients with, n (%) Placebo qw + TCS (n = 315) Dupilumab 300 mg q2w + TCS (n = 110) Dupilumab 300 mg qw + TCS (n = 315) Any TEAE 268 (85.1) 97 (88.2) 263 (83.5) TEAEs leading to discontinuation 25 (7.9) 2 (1.8) 9 (2.9) Death 0 0 1 (0.3) Any TE SAE 16 (5.1) 4 (3.6) 10 (3.2) Nasopharyngitisa,b 62 (19.7) 25 (22.7) 62 (19.7) Dermatitis atopica,b 147 (46.7) 22 (20.0) 55 (17.5) Injection-site reactiona,b 25 (7.9) 16 (14.5) 61 (19.4) Conjunctivitisb,c 25 (7.9) 15 (13.6) 61 (19.4) aPatients with ≥ 1 such event. bMedDRA PT. cNarrow conjunctivitis including MedDRA PTs of conjunctivitis, conjunctivitis allergic, conjunctivitis bacterial, conjunctivitis viral, and atopic keratoconjunctivitis. MedDRA, Medical Dictionary for Regulatory Activities; PT, Preferred Term; TEAE, Treatment-emergent adverse event; TE SAE, Treatment-emergent serious adverse event References: 1. C harman CR, et al. Arch Dermatol. 2004;140:1513-9. 2. S chmitt J, et al. J Allergy Clin Immunol. 2007;120:1389-98. 3. G erbens LA, et al. Allergy. 2017;72:146-63. 4. C halmers JR, et al. Br J Dermatol. 2016;175:69-79. 5. Macdonald LE, et al. Proc Natl Acad Sci U S A. 2014;111:5147-52. 6. Murphy AJ, et al. Proc Natl Acad Sci U S A. 2014;111:5153-8. 7. Gandhi NA, et al. Expert Rev Clin Immunol. 2017;13:425-37. 8. Blauvelt A, et al. Lancet. 2017;389:2287-303. Acknowledgments: Data fi rst presented at the 78th Annual Meeting of the American Academy of Dermatology (AAD 2020); Denver, CO, USA; March 20–24, 2020. Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifi er: LIBERTY AD CHRONOS (NCT02260986). Medical writing/editorial assistance provided by Toby Leigh Bartholomew, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Disclosures: Silverberg JI: AbbVie, Celgene, Eli Lilly, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Realm Therapeutics, Regeneron Pharmaceuticals, Inc. – investigator; AbbVie, Eli Lilly, Galderma, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, MedImmune (AstraZeneca), Menlo Therapeutics, Pfi zer, Realm Therapeutics, Regeneron Pharmaceuticals, Inc. – consultant; Regeneron Pharmaceuticals, Inc. – speaker. Lockshin B: Eli Lilly, Regeneron Pharmaceuticals, Inc. – investigator, speaker; Anacor, Dermira, Franklin Bioscience, LEO Pharma – investigator; AbbVie – investigator, speaker, consultant. Gooderham M: AbbVie, Akros, Amgen, Arcutis Antiobix, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus BioSciences, Dermira, Eli Lilly, Galderma, GSK, Janssen, Kyowa Kirin, LEO Pharma, Merck, MedImmune, Novartis, Pfi zer, Regeneron Pharmaceuticals, Inc., Roche, Sanofi Genzyme, Sun Pharma, UCB, Valeant/Bausch – investigator, advisor, and/or speaker. Chen Z, Gadkari A: Regeneron Pharmaceuticals, Inc. − employees and shareholders. Rossi AB: Sanofi Genzyme − employee, may hold stock and/or stock options in the company. METHODS (CONT.) RESULTS (CONT.) Effi cacy RESULTS Safety CONCLUSIONS • Dupilumab + TCS signifi cantly improved the total POEM score over the 52-week study period, and signifi cant improvements were observed in all individual domains, with most patients reporting “mild” symptoms by the end of the study • More patients receiving dupilumab + TCS vs control reported “0 days” of signs and symptoms on the 7 POEM items at Week 52