Clinical Responses in Patients with Moderate-to-Severe Plaque Psoriasis Following Withdrawal and Re-treatment with Risankizumab or Switching from Ustekinumab to Risankizumab Kim A Papp,1 Andrew Blauvelt,2 Mary Flack,3 Yihua Gu,4 Elizabeth H Z Thompson5 1K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada; 2Oregon Medical Research Center, Portland, OR, USA; 3Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 4AbbVie Inc., North Chicago, IL, USA; 5AbbVie Inc., Redwood City, CA, USA 1. Papp KA, et al. N Engl J Med 2017; 376: 1551-60. • To assess the efficacy following drug withdrawal and re-treatment with risankizumab or switching from ustekinumab to risankizumab at week 24 of the open label extension (OLE). • Switching treatment to risankizumab in patients initially treated with ustekinumab resulted in higher clinical responses, as measured by increases in PASI and sPGA responses at 24 weeks. • Re-treatment with two doses (OLE baseline and week 12) of 90 mg of risankizumab following risankizumab withdrawal also resulted in return of substantial clinical benefit. • The rates of adverse events through 24 weeks of OLE were as expected for the population and similar to those observed in the parent study. • Risankizumab is a humanized IgG1 monoclonal antibody that inhibits IL-23 by binding its p19 subunit. • In a phase 2 trial, risankizumab demonstrated superiority over ustekinumab in patients with moderate-to-severe plaque psoriasis. STUDY DESIGN AND PATIENTS • In the phase 2 (“parent”) study,1 166 patients with moderate-to- severe plaque psoriasis were randomized to receive subcutaneous injections of risankizumab (18 mg single dose at week 0, or 90 or 180 mg at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, based on body weight at weeks 0, 4, and 16). • Patients were followed up through week 48 during the double-blind period. • Patients (N=110) who completed 48 weeks in the parent study or who failed to achieve 50% improvement in psoriasis area and severity index (PASI 50) response between weeks 24 and 48 were eligible to enter the OLE (Figure 1). • In this ongoing OLE, all patients received 90 mg risankizumab at baseline and every 12 weeks thereafter, regardless of their response level at the end of the parent study. • Patients who failed to achieve PASI 90 responses in the OLE could increase their dose to 180 mg risankizumab starting at week 12; however, all patients received 90 mg risankizumab for the study period reported here. EFFICACY AND SAFETY ANALYSES • In this preliminary analysis, data through week 24 of the OLE from all entering patients were included. • The following efficacy endpoints were assessed at week 24 of OLE: – PASI 90, 90% improvement in Psoriasis Area and Severity Index – PASI 100, 100% improvement in Psoriasis Area and Severity Index – sPGA 0/1, static Physician Global Assessment score of clear or almost clear – sPGA 0, static Physician Global Assessment score of clear • Non-responder imputation (NRI) was used for missing efficacy data. • Treatment-emergent adverse events (TEAE) were defined as any adverse events occurring after the first dose of the study drug in the OLE through 24 weeks of OLE and within 105 days after the last dose of study drug (if the patient discontinued treatment during OLE). Figure 1. Study Design of Phase 2 Trial of Risankizumab in Psoriasis Patients 16Week 0 4 12 4824 = dose R a n d o m is e d 1 :1 :1 :1 Risankizumab 18 mg s.c. a N=40 Ustekinumab 45/90 mg s.c. b N=43 Risankizumab 180 mg s.c. N=41 Risankizumab 90 mg s.c. N=42 1 o Endpoint: PASI 90 at Week 12 16Week 0 12 24 OLE Week 24: E cacy and safety N=22 N=28 N=33 N=27 // // // // Risankizumab 90 mg s.c. d Double-Blind Period (N=166) Open-Label Extension (N=110) Follow-up c a. Placebo only at weeks 4 and 16. b. Used as per label (45 mg or 90 mg in patients with body weight ≤100 kg or >100 kg at randomization, respectively). c. Patients completing week 48 of the “parent” study (NCT02054481) were eligible to enroll in the OLE (NCT02203851). Patients who failed to achieve at least 50% improvement from baseline in PASI (5% of patients overall) was nasopharyngitis. Table 2. Summary of Adverse Events Through Week 24 of OLEa 0 20 40 60 80 100 Pa tie nt s Ac hi ev in g PA SI 1 00 ( ) Week 12 Week 24Week 0Week 16 Risankizumab 90 mg s.c. Double-Blind Period Open-Label E tension Ustekinumab 45/90 mg Risankizumab 1 0 mg Risankizumab 90 mg Risankizumab 1 mg Treatment groups from parent study 4 .1 27.3 46.4 39.4 a 0 20 40 60 80 100 Pa tie nt s Ac hi ev in g sP G A 0 /1 ( ) Week 12 Week 24Week 0Week 16 Risankizumab 90 mg s.c. Double-Blind Period Open-Label E tension Ustekinumab 45/90 mg Risankizumab 1 0 mg Risankizumab 90 mg Risankizumab 1 mg Treatment groups from parent study 77. 72.7 67.9 69.7 a 0 20 40 60 80 100 Pa tie nt s Ac hi ev in g sP G A 0 ( ) Week 12 Week 24Week 0Week 16 Risankizumab 90 mg s.c. Double-Blind Period Open-Label E tension Ustekinumab 45/90 mg Risankizumab 1 0 mg Risankizumab 90 mg Risankizumab 1 mg Treatment groups from parent study 4 .1 31. 46.4 45.5 a Adverse Events, n (%) Risankizumab 18 mg N=22 Risankizumab 90 mg N=28 Risankizumab 180 mg N=33 Ustekinumab 45/90 mg N=27 Overall N=110 Any AEs 11 (50.0) 11 (39.3) 10 (30.3) 10 (37.0) 42 (38.2) Drug-related AEsb 0 1 (3.6) 0 1 (3.7) 2 (1.8) Any AE with toxicity of grade 3 or 4 1 (4.5) 1 (3.6) 0 2 (7.4) 4 (3.6) AE leading to study drug discontinuation 0 0 0 0 0 AEs of special interest 0 0 0 0 0 Infections 5 (22.7) 7 (25.0) 6 (18.2) 4 (14.8) 22 (20.0) Serious AEsc 1 (4.5)e 1 (3.6)f 1 (3.0)g 0 3 (2.7) Death 0 0 0 0 0 Life-threatening 0 0 0 0 0 Persistent or significant disability or incapacity 0 0 0 0 0 Requires or prolongs hospitalization 1 (4.5) 1 (3.6) 1 (3.0) 0 3 (2.7) Congenital anomaly or birth defect 0 0 0 0 0 Other medically im- portant serious event 1 (4.5) 0 0 0 1 (0.9) Most Common AEsd Nasopharyngitis 0 3 (10.7) 1 (3.0) 2 (7.4) 6 (5.5) Upper respiratory tract infection 0 0 2 (6.1) 0 2 (1.8) a. AEs through week 24 in all patients who entered OLE based on their initial treatment groups. b. Investigator assessed AE as possibly or probably related to study drug. c. A serious adverse event was defined as any adverse event that results in death, is immediately life-threatening, results in persistent or significant disability or incapacity, requires or prolongs hospitalization, is a congenital anomaly or birth defect, or is characterized on the basis of appropriate medical judgment as an important medical event that may jeopardize the patient and may require medical or surgical intervention. d. Most common AEs occurring in >5% of patients. e. One patient with basal cell carcinoma, carpal tunnel syndrome, and ulnar neuropathy. f. One patient with arthri- tis. g. One patient with thyroid goiter. Abbreviations: OLE=open-label extension; AEs=adverse events. REFERENCES DISCLOSURES KA Papp has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant, grants as an investigator from AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant. A Blauvelt has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant, grants as an investigator from AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Janssen, Leo, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, UCB, Valeant, and Vidac. M Flack is a full-time employee of Boehringer Ingelheim. Y Gu and EHZ Thompson are full-time employees of AbbVie and may own stock/options. Boehringer Ingelheim funded the studies (NCT02054481 and NCT02203851), contributed to its design, and participated in data collection. AbbVie participated in data analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Deepa Venkitaramani, PhD, of AbbVie. Presented at the Fall Clinical Dermatology Conference - 36th Anniversary • Las Vega, Nevada • October 12 – 15, 2017 INTRODUCTION OBJECTIVE MATERIALS & METHODS RESULTS CONCLUSIONS FC17PosterAbbViePappClinicalResponses.pdf