INTRODUCTION • Papulopustular rosacea is a phenotype of rosacea characterized by papules and pustules located centrally on the face1 • Oral antibiotics such as tetracyclines are first-line treatments for patients whose disease does not respond to topical therapies or for patients with multiple papules and pustules2 • Sarecycline is a narrow-spectrum antibiotic approved by the US Food and Drug Administration in 2018 for treatment of moderate to severe acne vulgaris3 • Because of the well-established role for oral tetracyclines in rosacea and to limit emergence of antibiotic-resistant bacteria, a pilot study was conducted to assess oral sarecycline in adults with papulopustular rosacea (Clinicaltrials.gov identifier: NCT04555525) METHODS • This was a prospective, parallel-group, 12-week, randomized, investigator-blinded, pilot study of oral sarecycline treatment for adults with moderate to severe papulopustular rosacea (Figure 1) • Eligible participants were adults (aged ≥18 years) with moderate or severe rosacea based on Investigator Global Assessment (IGA) rating with ≥15 and ≤50 facial papules/ pustules and ≤2 facial nodules • Statistical analyses were conducted on an intention-to- treat basis; all tests were 2-sided and interpreted at a 5% significance level Figure 1. Study Design AE, adverse event; IGA, Investigator Global Assessment; QD, once daily; R, randomization; SGA, Subject Global Assessment. RESULTS Disposition and Baseline Characteristics • 102 adults with moderate-to-severe papulopustular rosacea were enrolled; 97 completed the study (sarecycline [n=72]; multivitamin [n=25]) • Most participants were female (n=80 [82%]) and white (n=95 [98%]), with mean (standard deviation) age of 52.4 (14.5) years Efficacy • Sarecycline was associated with significantly greater percentage of participants achieving IGA endpoint at week 12 vs multivitamin (coprimary endpoint; P<0.0001; Figure 2) – Significant differences in IGA score in favor of sarecycline vs multivitamin were observed as early as week 4 (21% vs 8%; P<0.0001) Figure 2. Participants Achieving IGA Scores of Clear/Almost Clear at Week 12 (Coprimary Endpoint) IGA, Investigator Global Assessment. • Sarecycline treatment was associated with statistically significantly greater reduction in inflammatory lesion count at week 12 vs multivitamin (coprimary endpoint; P<0.0001; Figure 3) – Rapid reduction in inflammatory lesion count was observed with sarecycline vs multivitamin as early as week 4 (Figure 3) Figure 3. Percent Change From Baseline in Inflammatory Lesion Counts Grey shading indicates coprimary endpoint at week 12. Secondary Endpoints and Skin Symptoms • At week 12, absent or trace ratings were significantly better in the sarecycline vs multivitamin group for facial symptoms of burning (P=0.038), erythema (P<0.0001), and pruritus (P=0.023; Figure 4); significant differences were also observed for absent or trace dryness (P=0.02) and oiliness (P=0.039) Figure 4. Participants With Absent/Trace in Facial Symptoms at Week 12 Safety • 26 adverse events (AEs) occurred in 16 participants in the sarecycline group – 7 rated as mild, 17 as moderate, 2 as severe – No serious AEs reported • Sarecycline was discontinued in 3 participants, with 2 AEs (headache and gastroenteritis) considered probably related to sarecycline • AEs of interest with a tetracycline derivative that occurred in the sarecycline group were nausea (n=2), headache (n=2), and facial sunburn (n=2) Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study Evaluating Efficacy and Safety James Q. Del Rosso, DO,1 Leon H. Kircik, MD,2-6 Cheryl Effron, MD,7 Zoe D. Draelos, MD8 1JDR Dermatology Research and Thomas Dermatology, Las Vegas, NV; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Indiana University Medical Center, Indianapolis, IN; 4Physicians Skin Care, PLLC, Louisville, KY; 5DermResearch, PLLC, Louisville, KY; 6Skin Sciences, PLLC, Louisville, KY; 7Cosmetic Dermatology of Orange County, Huntington Beach, CA; 8Dermatology Consulting Services, PLLC, High Point, NC Acknowledgments: This study was supported by Almirall, LLC. Medical writing, editorial assistance, and graphical support were provided under the direction of the authors by MedThink SciCom. References: 1. Dahl. Rosacea: pathogenesis, clinical features, and diagnosis. In: Post TW, ed. UpTo- Date. Waltham, MA: Wolters Kluwer; 2020. 2. Maier. Management of rosacea. In: Post TW, ed. UpToDate. Waltham, MA: Wolters Kluwer; 2020. 3. Sarecycline [package insert]. Exton, PA: Almirall; 2020. CONCLUSIONS • In this pilot study, oral sarecycline demonstrated effectiveness for treatment of papulopustular rosacea in adults as early as 4 weeks based on IGA scores and reductions in inflammatory lesion counts • Sarecycline improved facial symptoms, including burning, erythema, and pruritis • Sarecycline was associated with a favorable safety and tolerability profile, with AEs consistent with prior studies • Additional studies are warranted to further evaluate oral sarecycline as treatment for papulopustular rosacea 1 Enrolled participants (N=102) Participants completing study (N=97) Oral sarecycline, weight-based dose, QD (n=72) Oral multivitamin, 1 tablet, QD (n=25) R 3:1 Baseline Week 12Week 8Week 4 Coprimary outcome measures at Week 12 • Percentage of participants with IGA score of clear or almost clear • Percent reduction of inflammatory lesions Secondary Endpoints and Safety and Tolerability Assessments Assessments: • Participants with IGA score of clear/almost clear at 4 and 8 wk • Reduction of inflammatory lesions at weeks 4 and week 8 • SGA (rated at each study visit) • AEs • Local signs and symptoms (facial skin) Figure 1 2 75 16 0 20 40 60 80 100 Clear/Almost clear P ar tic ip an ts , % Sarecycline (n=72) Multivitamin (n=25) P<0.0001 Figure 2 3 -56 -71 -80 -31 -44 -60 -100 -80 -60 -40 -20 0 0 4 8 12 Sarecycline (n=72) Multivitamin (n=25) P<0.0001 P=0.0002 P<0.0001 Figure 3 Time, wk R ed uc tio n fr om b as el in e, % 4 96 63 94 76 12 76 0 20 40 60 80 100 Burning Erythema Pruritis P ar tic ip an ts , % Sarecycline (n=72) Multivitamin (n=25) P=0.023P=0.038 P<0.0001