OP0226\u2005TOWARDS DEVELOPMENT OF AN ULTRASOUND ENTHESITIS SCORE IN PSORIATIC ARTHRITIS: 24-WEEK RESULTS FROM THE PHASE III RANDOMISED ULTIMATE STUDY

Abstract

Background: Enthesitis is a key clinical domain and imaging hallmark of psoriatic arthritis (PsA). Ultrasound (US) is a highly sensitive tool for detecting synovitis and enthesitis in PsA. The Outcome Measures in Rheumatology Initiative (OMERACT) has developed an US definition and scoring system of enthesitis for clinical studies.1 The ULTIMATE study (NCT02662985) is the first large double-blind (DB), placebo-controlled phase IIIb study designed to demonstrate a rapid and significant benefit of subcutaneous secukinumab vs. placebo on US detected synovitis in patients with PsA.2 Objectives: To report the enthesitis response to secukinumab over 24 weeks using two novel US composite enthesitis scores. Methods: This was a 52-week study consisting of a 12-week DB, a 12-week open-label (OL) and a 6-month extension period.2 Inclusion criteria required ≥1 clinical enthesitis as per SPARCC enthesitis index, but not US-assessed enthesitis.2 Patients were randomised (1:1) to either weekly secukinumab (300 or 150 mg according to severity of skin psoriasis) or placebo followed by 4-weekly dosing thereafter. All placebo patients switched to OL secukinumab (placebo-secukinumab) at Week 12. Throughout the study, enthesitis was assessed with SPARCC and US. Six anatomical sites were assessed bilaterally with US: insertions of lateral epicondyle tendons, quadriceps, patellar ligaments (distal and proximal insertions), Achilles tendons and plantar fascia. Two exploratory global OMERACT-US enthesitis scores were tested: Definition 1 combining power Doppler (PD; 0–3) and Grey Scale (0–1) inflammation and Definition 2 rating PD only (0–3) across the six anatomical sites. Data were analysed with mixed-effect model repeated measures (MMRM) up to Week 12 and as observed from Week 12 to 24. The comparison of OMERACT-US enthesitis score within treatment groups was tested with paired and between treatment groups with unpaired t-tests. Results: Of 166 patients enrolled, 93% completed 24 weeks of treatment (secukinumab, 95%; placebo-secukinumab, 92%). The average clinical enthesitis count at baseline was 4. Since the presence of PD was not a mandatory inclusion criterion, a higher proportion of patients met Global OMERACT-US enthesitis score with Definition 1 vs. Definition 2 (81% vs. 33%) at baseline (Table). Mean reduction from baseline to Week 24 in SPARCC enthesitis index was 3 each for initial secukinumab and placebo-secukinumab groups. Resolution of enthesitis (SPARCC) was 46% for initial secukinumab and 54% for placebo-secukinumab groups at Week 24. A comparable decrease in OMERACT-US enthesitis (Definition 1 and 2) score was observed from baseline to Week 24 for initial secukinumab and placebo-secukinumab groups (Figure). Conclusion: A consistent clinical and US response on enthesitis was shown through 24 weeks across initial secukinumab and placebo switcher groups. While ULTIMATE has demonstrated the responsiveness of these global OMERACT-US enthesitis scores, further work is required to test these scores in PsA cohorts with inclusion criteria for both clinical and US enthesitis. References: [1]Balint PV, et al. Ann Rheum Dis. 2018;77:1730-5. [2]D’Agostino MA, et al. Arthritis Rheumatol. 2020;72(suppl 10). Disclosure of Interests: Maria-Antonietta D’Agostino Speakers bureau: Sanofi, Novartis, BMS, Janssen, Celgene, AbbVie, UCB pharma and Eli Lilly, Consultant of: Sanofi, Novartis, BMS, Janssen, Celgene, AbbVie, UCB pharma and Eli Lilly, Philip G Conaghan Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis and Pfizer, Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis and Pfizer, Corine Gaillez Shareholder of: Novartis and BMS, Employee of: Novartis, Maarten Boers Consultant of: BMS, Novartis, Pfizer, and GSK, Esperanza Naredo Speakers bureau: AbbVie, Roche, BMS, Pfizer, UCB, Eli Lilly, Novartis, Janssen and Celgene, Consultant of: AbbVie, Novartis and BMS, Grant/research support from: Eli Lilly, Philippe Carron Speakers bureau: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Consultant of: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Grant/research support from: UCB, MSD and Pfizer, Petra Hanova: None declared, Tomas Cazenave: None declared, Catherine Bakewell Speakers bureau: AbbVie, Novartis, Sanofi Genzyme, and consulting honoraria from Pfizer, UCB, and Janssen, Consultant of: AbbVie, Novartis, Sanofi Genzyme, and consulting honoraria from Pfizer, UCB, and Janssen, Anne-Marie Duggan Employee of: Novartis, Punit Goyanka Employee of: Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Roche and UCB pharma