Boni Elewski1, Alan Menter2, Jeffrey Crowley3, Stephen Tyring4, Yang Zhao5, Simon Lowry5, Stephen Rozzo5, Alan Mendelsohn5, Jeffrey Parno5, Kenneth Gordon6 Sustained and Improved Efficacy of Tildrakizumab from Week 28 to Week 52 in Treating Moderate-to-Severe Plaque Psoriasis 1. Department of Dermatology, The University of Alabama at Birmingham, Birmingham, Alabama USA; 2. Division of Dermatology, Baylor University Medical Center, Dallas, TX, USA; 3. Bakersfield Dermatology, Bakersfield, CA, USA; 4. Department of Dermatology, University of Texas Health Science Center, Houston, TX, USA; 5. Sun Pharmaceutical Industries, Princeton, NJ, USA; 6. Medical College of Wisconsin, Milwaukee, WI, USA • Psoriasis is a common, chronic, and immune- mediated skin disease, affecting 3.2% of the US population. Approximately 7.4 million people in the US have psoriasis1. • Psoriasis is characterized by painful, pruritic, well-demarcated, erythematous plaques with silver scale1,2, and often negatively impacts patients’ overall health, quality of life, productivity, and interpersonal relationship2-4. • Tildrakizumab is a high-affinity, humanized, IgG1 κ, anti-interleukin–23 monoclonal antibody designed to block interleukin-23 p195. It is administered subcutaneously once every 12 weeks, after two initial doses administered 4 weeks apart5. • Two phase-3, double-blind, randomized controlled trials (reSURFACE 1: NCT01722331; reSURFACE 2: NCT01729754) demonstrated efficacy and safety of tildrakizumab in the treatment of adult patients with moderate-to-severe plaque psoriasis over the first 28 weeks5. • This analysis evaluated longer-term data from these two trials to examine whether the efficacy is sustained or improved from week 28 through week 52. Study design of reSURFACE 1 • Overall, 352 patients on tildrakizumab 100 mg (male: 69.9%; mean baseline age: 44.9 years) and 313 on tildrakizumab 200 mg (male: 67.1%; mean baseline age: 46.4 years) were included. • The proportions of patients achieving PASI 100, PASI 90-99, PASI 75-89 and PASI 50-74 at week 28 were 25.9%, 38.4%, 25.3%, and 10.5% respectively for those on the 100 mg dose, and 24.6%, 24.3%, 19.5%, and 31.6% respectively for those on the 200 mg dose. • Week-52 PASI responses for patients treated with tildrakizumab 100 mg: − Among patients achieving week-28 PASI 100 (n=91), 75.8% maintained PASI 100, 18.7% had PASI 90-99, 94.5% had PASI≥90, and all had PASI≥75 at week 52 − Among patients achieving week-28 PASI 90-99 (n=135), 25.2% improved to PASI 100, 60.7% maintained PASI 90-99, and 10.4% had PASI 75- 89 at week 52 − Among patients achieving week-28 PASI 75-89 (n=89), 6.7% improved to PASI 100, 27.0% improved to PASI 90-99, and 40.4% maintained PASI 75-89 at week 52 − Among patients achieving week-28 PASI 50-74 (n=37), 18.9% improved to PASI 100, 10.8% improved to PASI 90-99, 35.1% improved to PASI 75-89, and 24.3% maintained PASI 50-74 at week 52 Study design of reSURFACE 2 • Week-52 PASI responses for patients treated with tildrakizumab 200 mg: − Among patients achieving week-28 PASI 100 (n=77), 84.4% maintained PASI 100, 11.7% had PASI 90-99, 96.1% had PASI≥90, and all had PASI≥75 at week 52 − Among patients achieving week-28 PASI 90-99 (n=76), 32.9% improved to PASI 100, 48.7% maintained PASI 90-99, and 17.1% had PASI 75- 89 at week 52 − Among patients achieving week-28 PASI 75-89 (n=61), 8.2% improved to PASI 100, 32.8% improved to PASI 90-99, and 39.3% maintained PASI 75-89 at week 52 − Among patients achieving week-28 PASI 50-74 (n=99), 6.1% improved to PASI 100, 14.1% improved to PASI 90-99, 32.3% improved to PASI 75-89, and 41.4% maintained PASI 50-74 at week 52 • Among patients who achieved week-28 PASI≥90 with either dose of tildrakizumab, 88.9-89.4% maintained PASI≥90 at week 52. • Overall, 91.1% patients on the 100 mg dose and 93.9% on the 200 mg dose with week-28 PASI≥75 maintained PASI≥75 at week 52. • In addition, 33.7%-41.0% of patients with week-28 PASI 75-89 improved to PASI≥90. • Among patients with week-28 PASI 50-74, 20.2-29.7% achieved PASI≥90 and 52.5- 64.9% achieved PASI≥75 at week 52. • Overall, 2.6% of patients on the 100 mg (9 out of 352) or 200 mg (8 out of 313) dose had week-52 PASI<50. Baseline Characteristics • Among patients with moderate-to-severe psoriasis treated with tildrakizumab 100 or 200 mg at weeks 0, 4, then every 12 weeks, those who achieved week-28 PASI≥50 and continued on the same dose had sustained or improved efficacy from week 28 through week 52. • The majority patients who achieved week-28 PASI≥75 or PASI≥90 maintained PASI≥75 or PASI≥90 at week 52. • More than half of partial responders (PASI 50- 74) at week 28 eventually achieved PASI≥75 and at least 1 in 5 achieved PASI≥90 at week 52. INTRODUCTION METHODS • Both phase-3 trials randomized adult patients with moderate-to-severe plaque psoriasis to receive tildrakizumab 100 mg or tildrakizumab 200 mg at weeks 0, 4, then every 12 weeks, and used three-part study design − Part 1 (week 0-12) randomized patients to: tildrakizumab 100 mg, tildrakizumab 200 mg, placebo, or etanercept 50mg (in reSURFACE 2) − Part 2 (week 12-28) re-randomized placebo patients to tildrakizumab; − Part 3 (week 28-64, reSURFACE 1; week 28-52, reSURFACE 2) re-randomized patients with Psoriasis Area and Severity Index (PASI) response ≥50% to the same, a higher or a lower dose of tildrakizumab, or placebo based on their week-28 PASI responses • This analysis included only patients treated with the same dose of tildrakizumab (100 mg or 200 mg) throughout the first 52 weeks. • Four mutually exclusive groups were created based on patients’ week-28 PASI response: PASI 100, PASI 90-99, PASI 75-89 and PASI 50-74. • Baseline characteristics and PASI responses at week 52 (observed data) were analyzed for each week-28 PASI-response group. RESULTS CONCLUSIONS REFERENCES 1. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516. 2. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-850. 3. Pariser D, Schenkel B, Carter C, et al. A multicenter, non-interventional study to evaluate patient-reported experiences of living with psoriasis. J Dermatolog Treat. 2016;27(1):19- 26. 4. Vanderpuye-Orgle J, Zhao Y, Lu J, et al. Evaluating the economic burden of psoriasis in the United States. J Am Acad Dermatol. 2015;72(6):961-967 e965. 5. Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390(10091):276-288. ACKNOWLEDGMENTS Dr. Peter Sun from Kailo Research Group provided writing support on this poster, with funding from SUN Pharmaceutical Industries. DISCLOSURES Drs. Elewski, Menter, Crowley, Tyring and Gordon were investigators of the two phase-3 clinical trials for tildrakizumab (reSURFACE 1 and reSURFACE 2). Drs. Zhao, Lowry, Rozzo and Mendelsohn and Mr. Parno are employees of Sun Pharmaceutical Industries. Week-28 PASI Categories 100 90-99 75-89 50-74 ≥50 Tildrakizumab 100 mg Cohort Number of Patients 91 135 89 37 352 Mean Age (year, SD) 42.6 (14.1) 45.0 (13.1) 46.1 (13.1) 47.2 (13.8) 44.9 (13.5) Proportion of males (%) 69.2% 70.4% 66.3% 78.4% 69.9% Race (%) White 80.2% 86.7% 85.4% 70.3% 83.0% Black 3.3% 1.5% 3.4% 0.0% 2.3% Asian 6.6% 9.6% 9.0% 27.0% 10.5% Others 9.9% 2.2% 2.2% 2.7% 4.2% Weight (Kg): mean (SD) 83.0 (18.8) 87.4 (21.6) 94.5 (23.6) 83.4 (22.4) 87.6 (21.9) BMI3 (kg/m2): mean (SD) 28.1 ( 5.7) 29.2 ( 6.7) 31.9 ( 7.7) 28.4 ( 7.1) 29.5 ( 6.9) Body Surface Area: % (SD) 28.9 (16.1) 33.5 (18.6) 32.0 (16.6) 35.7 (19.9) 32.2 (17.7) Disease Duration: years (SD) 14.3 (10.9) 16.8 (11.1) 17.8 (12.8) 14.3 (10.4) 16.2 (11.5) PASI: mean (SD) 18.5 ( 5.8) 20.9 ( 7.9) 19.6 ( 6.6) 20.6 ( 8.5) 19.9 ( 7.2) Previous medical conditions (%) Psoriatic arthritis 17.6% 16.3% 15.7% 18.9% 16.8% Cardiovascular diseases 25.3% 18.5% 29.2% 29.7% 24.1% Diabetes 8.8% 6.7% 7.9% 10.8% 8.0% Hypercholesterolemia 7.7% 5.2% 4.5% 8.1% 6.0% Hyperlipidemia 12.1% 4.4% 3.4% 8.1% 6.5% Hypertension 24.2% 18.5% 29.2% 27.0% 23.6% Obesity 1.1% 6.7% 7.9% 10.8% 6.0% Previously treated with biologics 12.1% 19.3% 13.5% 10.8% 15.1% Tildrakizumab 200 mg Cohort Number of Patients 77 76 61 99 313 Mean Age (year, SD) 45.8 (13.5) 45.4 (14.1) 47.8 (12.7) 46.9 (13.0) 46.4 (13.3) Proportion of males (%) 74.0% 69.7% 54.1% 67.7% 67.1% Race (%) White 81.8% 85.5% 68.9% 76.8% 78.6% Black 0.0% 2.6% 4.9% 2.0% 2.2% Asian 14.3% 10.5% 19.7% 21.2% 16.6% Others 3.9% 1.4% 6.5% 0.0% 2.6% Weight (Kg): mean (SD) 86.1 (24.5) 89.5 (22.5) 87.3 (19.0) 90.2 (24.4) 88.4 (23.0) BMI3 (kg/m2): mean (SD) 28.7 ( 7.5) 30.7 ( 8.9) 31.1 ( 7.5) 30.1 ( 6.7) 30.1 ( 7.6) Body Surface Area: % (SD) 30.8 (17.5) 29.6 (15.3) 31.7 (17.5) 33.2 (19.6) 31.4 (17.6) Disease Duration: years (SD) 16.8 (13.1) 17.9 (13.5) 18.7 (13.3) 17.6 (11.6) 17.7 (12.8) PASI: mean (SD) 20.7 ( 9.3) 19.7 ( 6.5) 20.1 ( 7.2) 20.1 ( 8.8) 20.1 ( 8.1) Previous medical conditions (%) Psoriatic arthritis 14.3% 17.1% 9.8% 22.2% 16.6% Cardiovascular diseases 24.7% 30.3% 32.8% 30.3% 29.4% Diabetes 9.1% 13.2% 11.5% 14.1% 12.1% Hypercholesterolemia 5.2% 5.3% 6.6% 5.1% 5.4% Hyperlipidemia 3.9% 6.6% 4.9% 8.1% 6.1% Hypertension 24.7% 29.0% 32.8% 30.3% 29.1% Obesity 2.6% 7.9% 9.8% 8.1% 7.0% Previously treated with biologics 18.2% 17.1% 19.7% 17.2% 17.9% 75.8% 25.2% 6.7% 18.9% 45.6% 34.6% 33.0% 18.7% 60.7% 27.0% 10.8% 43.8% 39.0% 36.1% 5.5% 10.4% 40.4% 35.1% 8.4% 17.5% 19.3% 3.7% 20.2% 24.3% 2.2% 7.3% 9.1% 5.6% 10.8% 1.6% 2.6% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% PASI 100 (n=91) PASI 90-99 (n=135) PASI 75-89 (n=89) PASI 50-74 (n=37) PASI ≥90 (n=226) PASI ≥75 (n=315) PASI ≥50 (n=352) PASI 100 PASI 90-99 PASI 75-89 PASI 50-74 PASI <50 W e e k -5 2 P A S I R e sp o n se ( % ) Week-28 PASI Groups 84.4% 32.9% 8.2% 6.1% 58.8% 44.4% 32.3% 11.7% 48.7% 32.8% 14.1% 30.1% 30.8% 25.6% 3.9% 17.1% 39.3% 32.3% 10.5% 18.7% 23.0% 1.3% 16.4% 41.4% 0.7% 5.1% 16.6% 3.3% 6.1% 0.9% 2.6% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% PASI 100 (n=77) PASI 90-99 (n=76) PASI 75-89 (n=61) PASI 50-74 (n=99) PASI ≥90 (n=153) PASI ≥75 (n=214) PASI ≥50 (n=313) PASI 100 PASI 90-99 PASI 75-89 PASI 50-74 PASI <50 W e e k -5 2 P A S I R e sp o n se ( % ) Week-28 PASI Groups Week-52 PASI Responses by Week-28 PASI Categories: Tildrakizumab 100 mg Week-52 PASI Responses by Week-28 PASI Categories: Tildrakizumab 200 mg Notes: PASI= Psoriasis Area and Severity Index; SD=standard deviation; BMI=body mass index