POS0020 EFFICACY AND SAFETY OF SECUKINUMAB IN PATIENTS WITH ROTATOR CUFF TENDINOPATHY: A 24-WEEK, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II PROOF-OF-CONCEPT TRIAL

Abstract

Background:Rotator cuff tendinopathy (RC TP) is a multifactorial condition and one of the most common causes of musculoskeletal burden. Current standard of care (SoC) is limited to pain relief with NSAIDs and physiotherapy. Recent evidence indicates that IL-17A-expressing tendon-resident immune cells are present in human overuse tendinopathy, and IL-17A levels are increased in early human tendinopathic tissue samples [1, 2]. Secukinumab (SEC) is a fully human, monoclonal antibody that binds to and neutralises IL-17A.Objectives:To evaluate the efficacy and safety of SEC in patients with active overuse RC TP refractory to oral NSAIDs/acetaminophen, physiotherapy or corticosteroid injections.Methods:96 patients with symptomatic RC TP with no or <50% rupture were randomly assigned to receive seven subcutaneous injections of SEC 300 mg or placebo (PBO) at baseline and Weeks 1, 2 and 3, followed by every 4 weeks starting at Week 4. The primary endpoint was change from baseline in the Western Ontario Rotator Cuff (WORC) index score at Week 14 for SEC vs PBO (two-sided p<0.1). Secondary endpoints included, visual analogue scale (VAS) pain score, Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) score, American Shoulder and Elbow Surgeons Shoulder Evaluation Form (ASES), EQ-5D-5L score and patient global assessment (PGA) score. All endpoints were assessed through 24 weeks.Results:Clinically relevant improvement in both SEC and PBO groups on top of SoC treatment was observed, with no statistically significant difference demonstrated in the full study population on physical symptoms and function (Table 1). Similar results were observed in the secondary endpoints with marked improvement in both groups over time. Exploratory post-hoc analyses in a subpopulation of 39% of the study subjects with non-acute, moderate to severe disease, SEC provided significant and clinically relevant improvements vs PBO through Week 24 in total WORC score (overall treatment difference: 19.2, p <0.01) and pain (VAS, overall treatment difference: 15, p = 0.02) with early effect observed after two weeks (Figure 1). A favourable treatment effect in the more severe subgroup was demonstrated in other patient-reported outcomes. No serious adverse events were reported.Conclusion:Although SEC did not demonstrate a significant benefit vs PBO in the overall patient population with active overuse RC TP, SEC did provide benefit in the subpopulation with non-acute, moderate to severe disease. Larger clinical trials of SEC in this area are warranted.