ACKNOWLEDGEMENTS: Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics; Ortho Dermatologics is a division of Bausch Health US, LLC • Presented at the 2022 Fall Clinical Dermatology Conference • October 20-23, 2022 • Las Vegas, NV NUMBER NEEDED TO TREAT (NNT) WHAT IS NNT? � NNT is a metric for quantifying effect sizes of clinically relevant study endpoints1 � NNT represents the number of patients needed to treat to achieve an additional cure in a given timeframe1-3 • For example, NNT=3 means that 3 patients would need to be treated with active drug rather than vehicle before expecting an additional responder2 HOW IS NNT USED? � In the absence of head-to-head studies, NNT may be used to indirectly assess comparative efficacy of treatments • Evaluation of NNT has been conducted in a variety of therapeutic areas, including psychiatry/neurology, cardiology, oncology, and dermatology � While a clinically relevant NNT threshold has not been established for acne, lower values indicate more favorable treatment (larger effect size) versus vehicle HOW IS NNT CALCULATED? � NNT is the reciprocal of the absolute risk reduction (ARR), rounded up to the nearest whole number1-3 WHAT ARE SOME LIMITATIONS OF NNT? Evaluates one binary outcome (eg, week 12 treatment success)2,4 No consideration of drug tolerability or study design/ population differences1-4 Clinical meaning subject to interpretation5 Bene�ts of a well- designed vehicle subtracted from active treatment,a leading to higher NNT values aDue to the potential of a well-designed vehicle to result in higher efficacy rates in the control group. Benefit of Topical Combination Therapy for Acne Treatment: Analysis of Effect Size Using Number Needed to Treat Steven R Feldman, MD, PhD1; George Han, MD, PhD2; Valerie Callender, MD3,4; Leon H Kircik, MD2,5,6; Linda Stein Gold, MD7; Neal Bhatia, MD8; Stephen K Tyring, MD, PhD9; Joshua A Zeichner, MD2 1Wake Forest School of Medicine, Winston-Salem, NC; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Howard University College of Medicine, Washington, DC; 4Callender Dermatology and Cosmetic Center, Glenn Dale, MD; 5Indiana University Medical Center, Indianapolis, IN; 6Physicians Skin Care, PLLC, DermResearch, PLLC, and Skin Sciences, PLLC, Louisville, KY; 7Henry Ford Hospital, Detroit, MI; 8Therapeutics Clinical Research, San Diego, CA; 9University of Texas Health Science Center, Houston, TX NNTs FOR COMBINATION TOPICAL ACNE TREATMENTS CONCLUSIONS � Given the paucity of head-to-head studies in acne, NNT may be used as a simple way to compare drug effects across clinical trials � IDP-126 gel (clindamycin phosphate 1.2%, BPO 3.1%, adapalene 0.15%) had the most favorable NNT values (lowest), with treatment success rates of ~50% � Due to the multifactorial pathogenesis of acne, a triple-combination topical treatment may result in clinical success more often than seen with two-ingredient combination products • These NNT values are supported by phase 2 study results, in which IDP-126 led to significantly greater treatment success rates at week 12 compared with its three component dyads in the same vehicle formulation7,8 ABBREVIATIONS ADAP, adapalene; BPO, benzoyl peroxide; CLIN, clindamycin phosphate; EGSS, Evaluator’s Global Severity Scale; IGA, Investigator’s Global Assessment; IL, inflammatory lesions; NIL, noninflammatory lesions; NNT, number needed to treat; TRET, tretinoin. REFERENCES 1. Citrome L, Ketter TA. Int J Clin Pract. 2013;67(5):407-11. 2. Citrome L. J Clin Psychiatry. 2011;72(3):412-3. 3. Manriquez JJ, et al. J Am Acad Dermatol. 2007;56(4):664-71. 4. McAlister FA. CMAJ. 2008;179(6):549-53. 5. Nguyen C, et al. Explor Res Clin Soc Pharm. 2021;2:100039. 6. Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/ 7. Stein Gold L, et al. Presented at the annual American Academy of Dermatology Meeting. March 25-29, 2022. 8. Stein Gold L, et al. Am J Clin Dermatol. 2022;23(1):93-104. AUTHOR DISCLOSURES SRF has received research, speaking and/or consulting support from Eli Lilly, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, LEO Pharma, Mylan, Celgene, Ortho Dermatologics Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. He is founder and part owner of Causa Research and holds stock in Sensal Health; GH is or has been an investigator, consultant/advisor, or speaker for AbbVie, Athenex, Boehringer Ingelheim, Bond Avillion, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, Janssen, LEO Pharma, MC2, Ortho Dermatologics, PellePharm, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB; VC has served as an investigator, consultant, or speaker for AbbVie, Galderma, L’Oréal, Ortho Dermatologics, and Vyne; LHK has acted as an investigator, advisor, speaker, and consultant for Ortho Dermatologics; LSG has served as investigator/consultant or speaker for Ortho Dermatologics, LEO Pharma, Dermavant, Incyte, Novartis, AbbVie, Pfizer, Sun Pharma, UCB, Arcutis and Lilly; NB has served as advisor, consultant, and investigator for AbbVie, Almirall, Biofrontera, BI, Brickell, BMS, EPI Health, Ferndale, Galderma, InCyte, ISDIN, J&J, LaRoche-Posay, LEO Pharma, Ortho Dermatologics, Regeneron, Sanofi, SunPharma, Verrica, and Vyne; SKT has acted as an investigator for Ortho Dermatologics; JAZ has served as advisor, consultant, or speaker for AbbVie, Allergan, Dermavant, Dermira, EPI Health, Galderma, Incyte, Johnson and Johnson, L’Oreal, Ortho Dermatologics, Pfizer, Procter and Gamble, Regeneron, Sun Pharma, UCB, Unilever, and Vyne. Objectives and Methods � The objective was to evaluate NNT values for combination topical acne treatments � NNT to achieve treatment success was calculated for 8 combination treatments: 7 dual-combinations (FDA approved) and 1 triple-combination (in development) � Treatment success was defined as ≥2-grade EGSS/IGA improvement and clear/almost clear skin at week 12 Results � Treatment success rates and calculated NNT values from 13 studies are shown in the Figure • Eleven studies enrolled patients with moderate-to-severe acne and 2 studies included those with mild and/or very severe acne; additional inclusion/exclusion criteria are shown � The lowest NNT values (most favorable) were achieved with IDP-126 gel—fixed-dose, triple combination clindamycin phosphate 1.2%, BPO 3.1%, adapalene 0.15%—which is in development for the treatment of acne IDP-126 Gel CLIN 1.2%, BPO 3.1%, ADAP 0.15% Treatment Success (%)a NNT (Calculated) Favors Treatment Severityc Age, y IL NIL 3, 4 ≥9 30-100 35-150 3, 4 ≥12 20-100 30-150 3 2, 3, 4 ≥12 20-50 30-100 3, 4 12-70 17-40 20-100 2, 3, 4, 5 ≥12 17-40 20-150 3, 4 12-70 20-40 20-100 3, 4 ≥9 20-100 30-150 3, 4 ≥12 20-100 20-100 Epiduo Forte Gel ADAP 0.3%, BPO 2.5% Epiduo Gel ADAP 0.1%, BPO 2.5% Acanya Gel CLIN 1.2%, BPO 2.5% Veltin Gel CLIN 1.2%, TRET 0.025% Onexton Gel CLIN 1.2%, BPO 3.75% Twyneo Cream TRET 0.1%, BPO 3% Ziana Gel CLIN 1.2%, TRET 0.025% 20.5 50.5 24.9 49.6 11.0 33.7 11.3 30.1 5.6 21.5 14.4 28.8 10.8 28.4 17.8 33.2 14.5 28.5 14.3 39.9 15.1 26.8 7.9 22.8 8.7 21.0 Vehicle Active treatment 5 4 5 7 6 7 6 7 8 9 4 9 7 Inclusion/Exclusion Criteriab aDefined as percentage of patients achieving ≥2-grade reduc tion from baseline in EGSS/IGA and clear/almost clear skin at week 12. Data for approved treatments were from prescribing information and/or FDA medical reviews.6 Data for IDP-126 were from t wo phase 3 studies.7 bInclusion/exclusion criteria were for facial acne or were not specified. cStudies evaluated severit y via 5- or 6 -point EGSS or IGA. Though there were slight dif ferences in definition, generally: 0=clear, 1=almost clear/minimal, 2=mild, 3=moderate, 4=severe, 5=ver y severe. 1 (% Success With Active Treatment − % Success With Vehicle) * 100