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
Authors: N. L. Millar, I. Mcinnes, L. Mindeholm, A. Seroutou, J. Praestgaard, U. Schramm, R. Levitch, E. Weber, D. Laurent, J. Rosen, G. Schett, R. Roubenoff, M. Schieker
Journal: Annals of the Rheumatic Diseases (2021)

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 &lt;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&lt;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 &lt;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. References: [1]Millar NL, et al. Sci Rep . 2016;6:27149. [2]Millar NL, et al. Nat Rev Rheumatol .2017;13:110-122. Table 1. Change from baseline in the SEC versus PBO groups in WORC index and pain (VAS) Visit SEC 300 mg PBO p-value Total treated population N=96 WORC Index percentage score (0 worst -100 best ) a Day 29 22.35 19.49 0.45 Day 99 37.00 37.77 0.87 Day 169 43.41 40.97 0.64 Pain (VAS, 0 best - 100 worst ) b Day 29 −26.04 −23.13 0.57 Day 99 −46.11 −40.56 0.28 Day 169 −52.23 −50.74 0.78 Post-hoc population* N=37 WORC Index percentage score (0 worst - 100 best ) c Day 29 30.09 10.84 0.002 Day 99 48.26 31.83 0.048 Day 169 55.98 35.24 0.028 Pain (VAS, 0 best - 100 worst ) d Day 29 −29.20 −14.85 0.125 Day 99 −51.48 −35.37 0.045 Day 169 −57.01 −46.64 0.217 a Day 1: SEC 42.47, PBO 40.47; b SEC 67.04, PBO 64.85; c SEC 35.93, PBO 32.90, d SEC 71.72, PBO 67.58. Day 1 values are given as absolute values to describe baseline WORC/Pain status *Post-hoc subpopulation: Baseline: (Disease duration 2-6 months) AND (WORC ≤40 OR Tear Thickness (Bauer) ≥1 OR Sein ≥2) PBO, placebo; SEC, secukinumab; SoC, standard of care; WORC, Western Ontario Rotator Cuff Index; VAS, visual analogue scale Figure 1. Post-hoc analysis of function (WORC) in the treatment groups in non-acute, moderate to severe subpopulation SEC SE, standard error; SEC, secukinumab; WORC, Western Ontario Rotator Cuff Index Disclosure of Interests: Neal L Millar Grant/research support from: Honoraria or research funding from Novartis and Stryker, Iain McInnes Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB, Linda Mindeholm Employee of: Employee of Novartis, Abdelkader Seroutou Employee of: Employee of Novartis, Jens Praestgaard Employee of: Employee of Novartis, Ursula Schramm Employee of: Employee of Novartis, Rafael Levitch Employee of: Employee of Novartis, Eckhard Weber Employee of: Employee of Novartis, Didier Laurent Employee of: Employee of Novartis, Jeffrey Rosen Consultant of: Research advisor for Novartis, Georg Schett Speakers bureau: Received speakers honoraria from Abbvie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, UCB, Ronenn Roubenoff Employee of: Employee of Novartis, Matthias Schieker Employee of: Employee of Novartis.