A RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING SECUKINUMAB 300 MG AND 150 MG AT WEEK 52 IN PATIENTS WITH ANKYLOSING SPONDYLITIS WHO DID NOT ACHIEVE INACTIVE DISEASE DURING AN INITIAL 16 WEEKS OF OPEN-LABEL TREATMENT WITH SECUKINUMAB 150 MG

Background: Ankylosing spondylitis (AS) is a chronic, systemic inflammatory condition characterized by inflammatory back pain and is associated with extra-musculoskeletal manifestations and systemic comorbidities. Secukinumab (SEC) doses of 150 mg and 300 mg are approved to treat AS, although no dose escalation studies are available in patients who have inadequate response to SEC 150 mg. Objectives: The ASLeap study (NCT03350815) estimated the difference in clinical response to SEC 300 mg vs 150 mg at Week (Wk) 52 in patients with AS who failed to achieve Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease status on SEC 150 mg at Wk 16. Methods: In this randomized, double-blind, parallel-group, multicenter, phase 4 study, 322 patients with AS were assigned to receive open-label SEC 150 mg administered per the label for 16 Wks (period 1). At Wk 16, patients who did not achieve inactive disease (ASDAS < 1.3) at Wks 12 and 16 were randomized 1:1 in a double-blind manner to SEC 150 mg or escalated to SEC 300 mg q4w to Wk 52 (period 2). The primary efficacy variable was achievement of ASDAS < 1.3 and the primary analysis time point was Wk 52. Secondary efficacy variables were achievement of ASDAS clinically important improvement ≥ 1.1, 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), Assessment of SpondyloArthritis international Society responses (ASAS20, ASAS40, and ASAS partial remission), and change from baseline in BASDAI, ASAS Health Index (ASAS-HI), and the Functional Assessment of Chronic Illness Therapy – Fatigue Scale (FACIT-F). Safety was evaluated by incidence of treatment-emergent adverse events (TEAEs) through Wk 52. No statistical hypothesis tests for superiority or equivalence were planned in the protocol and none were performed. Results: Of 279 patients receiving SEC 150 mg who completed the 16-wk open-label period 1, 22 (7.9%) achieved ASDAS < 1.3 at Wks 12 or 16 and continued receiving SEC 150 mg; 207 patients did not attain ASDAS < 1.3 at Wk 12 and Wk 16 and initiated period 2. Demographics and baseline disease characteristics were balanced between patients randomized to SEC 150 mg and SEC 300 mg, including the proportion of patients who were TNFi naive (SEC 150 mg: 73 [72.3%]; SEC 300 mg: 73 [69.5%]) ( Table 1 ). Approximately 60% of patients in either SEC group were HLA-B27 positive. After having an inadequate response to SEC 150 mg through Wk 16, patients receiving either dose of SEC experienced similar improvements at Wk 52 in disease activity as measured by achievement of ASDAS < 1.3, ASDAS clinically important improvement ≥ 1.1, BASDAI50, ASAS20, ASAS40, and ASAS partial remission; and mean changes in BASDAI, quality of life as measured by ASAS HI, and fatigue as measured by FACIT-F ( Figure 1 ). The incidence of TEAEs through Wk 52 was similar between patients receiving SEC 300 mg (63.4%) and 150 mg (68.6%). Table 1. Demographics and Baseline Disease Characteristics of Patients in Period 2 (safety set) Characteristic Secukinumab 150 mg → 300 mg N = 101 Secukinumab 150 mg → 150 mg N = 105 Age, mean (SD), years 48.5 (14.1) 47.0 (13.7) Female, n (%) 43 (42.6) 52 (49.5) BMI, mean (SD), kg/m 32.0 (8.0) 32.1 (7.7) HLA-B27 positive, n (%) 60 (59.4) 65 (61.9) Time since axial symptom onset, mean (SD), years 13.9 (11.7) 14.0 (12.5) Time since diagnosis of AS, mean (SD), years 4.7 (8.6) 5.1 (9.7) TNFi naive, n (%) 73 (72.3) 73 (69.5) History of extra-axial involvement, n (%) Peripheral arthritis 34 (33.7) 30 (28.6) Enthesitis 29 (28.7) 31 (29.5) Uveitis 13 (12.9) 17 (16.2) Psoriasis 14 (13.9) 14 (13.3) Dactylitis 7 (6.9) 4 (3.8) Inflammatory bowel disease 2 (2.0) 1 (1.0) AS, ankylosing spondylitis; BMI, body mass index; TNFi, tumor necrosis factor inhibitor. Conclusion: Patients with AS who did not achieve inactive disease by Wk 16 after receiving SEC 150 mg experienced similar clinical response and safety through Wk 52 regardless of dose escalation to SEC 300 mg or continuation on SEC 150 mg. Acknowledgements: This study was funded by Novartis Pharmaceuticals Corporation. Medical writing support was provided by Richard Karpowicz, PhD, CMPP, of Health Interactions, Inc, and was funded by Novartis Pharmaceuticals Corporation. This abstract was developed in accordance with Good Publication Practice (GPP3) guidelines. Authors had full control of the content and made the final decision on all aspects of this publication. Disclosure of Interests: Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB, Alan Kivitz Shareholder of: Amgen, Gilead, GSK, Novartis, Pfizer, and Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, GSK, Eli Lilly, Horizon, Merck, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Gilead, Janssen, Pfizer, Regeneron, Sanofi, and Sun Pharma, Marina Magrey Consultant of: Eli Lilly and Novartis, Grant/research support from: AbbVie, Amgen, and UCB, Jessica A. Walsh Consultant of: Amgen, Lilly, Novartis, and UCB, Grant/research support from: AbbVie and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, and UCB, Maria Greenwald Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, Galapagos, and Janssen, Renato Calheiros Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Farid Kianifard Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Chelsea Elam Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Kriti Nagar Employee of: Novartis Healthcare Pvt Ltd, Hyderabad, India, Adam Winseck Employee of: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, Lianne S. Gensler Consultant of: Galapagos, Eli Lilly, Janssen, and Pfizer, Grant/research support from: UCB Pharma, AbbVie, Amgen, and Novartis. Citation: , volume 81, supplement 1, year 2022, page 16Session: AxSpA drug treatment: new and old drugs (Oral Presentations)