Poster presented at the Winter Clinical Dermatology Conference, January 12–17, 2018, Lahaina, HI, USA INTRODUCTION • The OPTIMA (efficacy of optimized retreatment and step-up therapy with omalizumab in patients with chronic idiopathic/spontaneous urticaria [CIU/CSU]; NCT02161562) study was designed to address some of the key gaps in the knowledge of optimal CIU/CSU treatment with omalizumab1 • Omalizumab is approved for the treatment of adults and adolescents (12 years and above) with CIU/CSU who remain symptomatic despite H1-antihistamine treatment; in Canada the approved dosage is omalizumab 150 mg or 300 mg every 4 weeks2 • The treatment algorithm proposed by international guidelines states that the disease should be treated to complete resolution of symptoms3 • To date, no data evaluating the efficacy of step-up therapy in patients inadequately controlled with omalizumab 150 mg are available OMALIZUMAB DOSE STEP-UP AND TREATMENT RESPONSE IN PATIENTS WITH CHRONIC IDIOPATHIC/SPONTANEOUS URTICARIA (CIU/CSU): RESULTS FROM THE OPTIMA STUDY Wayne Gulliver,1 Gordon Sussman,2 Jacques Hébert,3 Charles W. Lynde,4 Kim A. Papp,5 William H. Yang,6 Olivier Chambenoit,7 Antonio Vieira,8 Frederica DeTakacsy,8 Lenka Rihakova8 1Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada; 2Department of Medicine, University of Toronto, Toronto, ON, Canada; 3Department of Medicine, Centre Hospitalier de l’Université Laval, Québec, QC, Canada; 4Lynde Institute for Dermatology, Markham, ON, Canada; 5Probity Medical Research Inc., Waterloo, ON, Canada; 6Ottawa Allergy Research Corporation, University of Ottawa Medical School, ON, Canada; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 8Novartis Pharmaceuticals Canada Inc., Dorval, QC, Canada Inclusion criteria • Men or women at least 18 years of age • Diagnosis of CIU/CSU and the presence of symptoms for ≥6 months prior to the screening visit • Patient must have been on an approved dose of nonsedating H1-antihistamine for CIU/CSU, and no other concomitant CIU/CSU treatment, for at least the 7 consecutive days immediately prior to the randomization visit and must have documented current use on the day of the randomization visit • UAS7 score ≥16 (scale 0−42) and itch component of UAS7 ≥8 (scale 0−21) during 7 days prior to randomization Exclusion criteria • Patients having a clearly defined underlying etiology for chronic urticaria other than CIU/CSU • Patients with urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma or leukemia, active atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch that could interfere with study outcomes • Patients with a history of malignancy of any organ system • Patients should stay on same approved dose of nonsedating H1-antihistamine during entire trial duration. No rescue medication was allowed METHODS Study design • OPTIMA is a Phase 3b, international, multicenter, randomized, open-label, noncomparator study • Patients with CIU/CSU who were symptomatic despite H1-antagonists at approved dose were randomized 4:3 to omalizumab 150 mg or 300 mg for 24 weeks (1st dosing period) • Based on weekly Urticaria Activity Score (UAS7), patients entered one of the following phases: treatment withdrawal (if UAS7 ≤6), step-up to 300 mg (if 150 mg initially and UAS7 >6 at Weeks ≥8 to 24), or continued treatment for 12 more weeks (if 300 mg initially and UAS7 >6 at Week 24) • Patients who relapsed (UAS7 ≥16) during the treatment withdrawal period were retreated with the same dose (omalizumab 150 mg or 300 mg every 4 weeks) during the 12-week second dosing period Table 1. Demographics and baseline characteristics Characteristic Omalizumab 150 mg (n=178) Omalizumab 300 mg (n=136) Overall (N=314) Age, mean (range), years 46.7 (18–79) 45.8 (20–78) 46.3 (18–79) Gender, % Male Female 27.0 73.0 27.2 72.8 27.1 72.9 Race, % White Asian Black American Indian/Alaska Native Other 76.4 8.4 5.6 1.1 8.4 83.1 7.4 4.4 2.2 2.9 79.3 8.0 5.1 1.6 6.1 Time to CIU/CSU symptoms, n (%) ≤1 year >1–≤2 years >2–10 years >10 years 28 (15.7) 25 (14.0) 84 (47.2) 41 (23.0) 22 (16.2) 25 (18.4) 54 (39.7) 35 (25.7) 50 (15.9) 50 (15.9) 138 (43.9) 76 (24.2) Baseline UAS7, mean (range) 29.7 (16.0–42.0) 30.0 (16.0–42.0) 29.8 (16.0–42.0) # Prior medications used for CIU/CSU, mean (range) 1.8 (0.0–12.0) 2.1 (0.0–8.0) 1.9 (0.0–12.0) CIU/CSU, chronic idiopathic/spontaneous urticaria; UAS7, weekly Urticaria Activity Score. • Of those patients with CIU/CSU treated with omalizumab 150 mg, 79.2% (141/178) had to be up-dosed to 300 mg • Step-up treatment to omalizumab 300 mg led to a mean improvement of 9.7 points in UAS7 when compared with the 150 mg dosing period • Of those patients who had not been well controlled by omalizumab 150 mg, 45.4% were well controlled by omalizumab 300 mg during the step-up phase, and 25.4% of these were even symptom free RESULTS Baseline characteristics Scan this QR code Visit the web at: http://novartis.medicalcongressposters.com/Default.aspx?doc=f1660 Mobile Friendly e-Prints 3 ways to instantly download an electronic copy of this poster to your mobile device or e-mail a copy to your computer or tablet Text Message (SMS) Text: Qf1660 to: 8NOVA (86682) US Only +18324604729 North, Central and South Americas; Caribbean; China +447860024038 UK, Europe & Russia +46737494608 Sweden, Europe Standard data or message rates may apply. • Step-up treatment improved the disease severity scenario4 REFERENCES 1. ClinicalTrials.gov – NCT02161562. 2. Xolair [product monograph]. Dorval, Quebec: Novartis Pharmaceuticals Canada Inc.; April 2017. 3. Zuberbier T, et al. Allergy. 2014;69:868–87. 4. Stull D, et al. EAACI 2014. FUNDING This study was funded by Novartis Pharmaceuticals Canada Inc. DISCLOSURES Authors declare the following, real or perceived conflicts of interest: WG, GS, JH, CWL, KAP, and WHY received honoraria as investigators and consultants. OC, AV, FdT, and LR are employees of Novartis Pharmaceuticals. ACKNOWLEDGMENTS The complete OPTIMA study team comprised: 35 active sites in the following countries: Argentina, Brazil, Canada, Chile, Dominican Republic, Guatemala, Mexico, and Panama; Syreon Clinical Research for project management and data management; Sumeet Sood, PhD, Novartis Healthcare Pvt Ltd, Hyderabad, India for medical writing and editorial support, which was funded by Novartis Pharma AG, Switzerland in accordance with Good Publication Practice (GPP3) guidelines; Novartis Pharmaceuticals Canada and Novartis in participating countries. All authors participated in the development of the poster and approved the final poster for presentation. Editorial assistance in the development of this poster was provided by Jessica Donaldson-Jones of Fishawack Communications, Abingdon, UK. This poster was previously presented at the 26th European Academy of Dermatology and Venereology Congress, September 13–17, 2017, Geneva, Switzerland. CONTACT INFORMATION Lenka Rihakova – Lenka.Rihakova@novartis.com; Antonio Vieira – Antonio.Vieira@novartis.com; Novartis Pharmaceuticals Canada: +1(514) 631 6775 314 randomized patients Omalizumab 150 mg, 178 patients Omalizumab 300 mg, 136 patients Figure 2. Patient randomization ratio Screen & Washout Omalizumab 150 mg Omalizumab 300 mg G ro u p A G ro u p B Follow- up UAS7 ≤6 UAS7 <16 Stop therapy Omalizumab 300 mg Omalizumab 150 mg R a n d o m iz a ti o n 4 :3 −5 to −1Week 0 4 8 12 16 2420 0 4 8 12 0 4 UAS7 ≤6 UAS7 <16 Stop therapy Omalizumab 300 mg Omalizumab 300 mg UAS7 ≥16 UAS7 ≥16 Screen 1st dosing Study treatment withdrawal 2nd dosing Follow- up 0 4 8 UAS7 >6 UAS7 >6 UAS7, weekly Urticaria Activity Score. Figure 1. OPTIMA study design. The study includes five phases: screening; initial dosing period; withdrawal; a second dosing period for retreatment, dose step-up, or dose extension based on UAS7 response; and follow-up. Well controlled 27 patients (15.2%) 314 randomized patients Omalizumab 150 mg 178 patients Discontinued 10 patients (5.6%) Discontinued 5 patients (3.7%) Omalizumab 300 mg 136 patients Well controlled 88 patients (64.7%) Extended treatment 43 patients (31.6%) Step-up 141 patients (79.2%) Figure 3. Patient disposition after first dosing period Week 24 n=141 Week 20 n=141 Week 16 n=141 Week 12 n=141 81.6% 5.7% 6.4% 4.2% 2.1% 100 80 60 40 20 0 Week 8 n=141 P ro p o rt io n o f p a ti e n ts s te p p in g u p ( % ) a) Proportion of patients stepping up at scheduled visits c) Mean UAS7 during the second dosing period with omalizumab 300 mg Baseline n=141 Week 4 n=136 Week 8 n=133 Week 12b n=130 Mean UAS7 Change from baseline 22.4 14.6 12.4 12.7 −7.8 −10.0 −9.7 −20 −10 0 10 20 30 40 M e a n (+ 9 5 % C I) U A S 7 M e a n c h a n g e fr o m b a s e li n e in U A S 7 M e a n (+ 9 5 % C I) U A S 7 M e a n c h a n g e (− 9 5 % C I) f ro m b a s e li n e in U A S 7 30.4 21.9 20.3 5.2 7.7 7.9 −8.5 −10.1 −22.3 −19.1 −16.8 −40 −30 −20 −10 0 10 20 30 40 Baseline n=141 Week 4 n=141 Week 8a n=141 Week 12 n=26 Week 16 n=18 Week 20 n=9 b) Mean UAS7 during the first dosing period with omalizumab 150 mg Mean UAS7 Change from baseline Figure 4. Proportion of patients stepping up and patient response to omalizumab 150 mg (first dosing) and 300 mg (step-up) 100 80 60 40 20 0 Well controlled (UAS7 ≤6) (N=130) Urticaria free (UAS7 =0) (N=130) P ro p o rt io n o f p a ti e n ts ( % ) n=59 25.4% 45.4% n=33 UAS7, weekly Urticaria Activity Score. Error bars represent 95% confidence level. Figure 5. Proportion of patients who were clinically well controlled (UAS7 ≤6) or urticaria free (UAS7 =0) at the end of step-up phase OBJECTIVES • Four objectives were to be answered in OPTIMA: − If a patient’s signs and symptoms of CIU/CSU are well controlled with omalizumab and the treatment is stopped, will the patient relapse? How long will it take until relapse? − If omalizumab treatment is restarted, will the patient respond to retreatment? − If the patient does not sufficiently respond to omalizumab 150 mg, will step-up therapy to 300 mg improve the signs and symptoms of CIU/CSU? − If the patient does not respond to 300 mg, will treatment extension improve the signs and symptoms of CIU/CSU? • This poster will cover the third question Baseline After step-up Well controlled (UAS7 ≤6) Mild (>6 UAS7 ≤16) Moderate (>16 UAS7 ≤28) Severe (UAS7 >28) P ro p o rt io n o f p a ti e n ts ( % ) 45.4% 23.8% 16.1% 14.6%UAS7 =0 25.4% 0% 1.4% 40.4% 58.1% 100 80 60 40 20 0 Figure 6. Disease severity distribution at baseline and after step-up UAS7, weekly Urticaria Activity Score. a81.56% (n=15) patients were stepped up to omalizumab 300 mg by Week 8. The data for Weeks 12 to 20 are only for patients responding to omalizumab 150 mg. b11 patients out of 141 did not complete the step-up period or did not submit the participant diary as per protocol. CI, confidence interval; UAS7, weekly Urticaria Activity Score. CONCLUSIONS • Of the patients with CIU/CSU treated with omalizumab 150 mg, 79.2% had to be up-dosed to 300 mg owing to insufficient symptom control • The mean UAS7 improvement after the first dosing period and step-up therapy was 8.0 points and 9.7 points, respectively • From the step-up patient group, 45.4% of patients achieved symptom control during the 3-month treatment with omalizumab 300 mg • Disease severity distribution was improved after dose step-up, with the majority of patients having well-controlled (45.4%) or mild (23.8%) disease