EFFICACY OF SECUKINUMAB IN ENTHESITIS-RELATED ARTHRITIS: RESULTS FROM A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, TREATMENT WITHDRAWAL, PHASE 3 STUDY (JUNIPERA)

Background Enthesitis-related Arthritis (ERA) is a category of juvenile idiopathic arthritis (JIA) characterised by heterogeneous and insidious manifestations comprising axial and/or peripheral arthritis, and enthesitis. 1 Secukinumab (SEC) demonstrated efficacy and safety in both ERA and juvenile psoriatic arthritis (JPsA) in the JUNIPERA trial. 2 Objectives To evaluate the rate of flare risk reduction and efficacy of SEC on axial and peripheral manifestations in patients (pts) with active ERA. Methods ERA pts (2 to <18 years of age) with active disease (both ≥3 active joints and ≥1 active enthesitis site) were included. In the open-label (OL) treatment-period (TP)1, s.c. SEC (75/150 mg in pts <50/ ≥50 kg) was administered at baseline (BL), and at Week (Wk) 1–4, 8 and 12. Pts who achieved at least JIA-ACR30 response at Wk 12 were randomised into the double-blinded TP2 to continue SEC or placebo (PBO) every 4 wk until a disease flare, or up to Wk 100. The primary endpoint was time to flare in ERA and JPsA pts. The juvenile spondyloarthritis disease activity Index (JSpADA) is a disease activity assessment tool that contains 8 items to measure axial and peripheral disease activity. 3 Evaluation of axial and peripheral manifestations at the end of TP1 and TP2 in pts who experienced these symptoms at BL included modified Schober test (lumbar flexion), inflammatory back pain, FABER (Flexion, ABduction, External Rotation) test, JIA-ACR responses, Juvenile Arthritis Disease Activity Score (JADAS)-27, and resolution of enthesitis and dactylitis for peripheral disease. These outcomes were also used to assess JIA disease course at the end of TP2. Results A total of 52/86 (60.5%) pts with ERA were enrolled in the OL period TP1 (mean age, 13.7 years; male, 78.8%). In total, 51/52 (98.1%) pts completed TP1 and 41/44 (93.2%) completed TP2. At BL, mean JADAS-27 was 14.8, mean JSpADA index was 3.9, mean enthesitis and dactylitis counts were 2.7 and 0.4, respectively, mean number of active joints was 6.2 and of mean joints with limited range of motion 4.9. The relative risk reduction of experiencing a disease flare in TP2 was 55% (HR 0.45, 95% CI: 0.16–1.28, p=0.075) in ERA pts (Figure 1). The overall axial and peripheral disease symptoms improved over time and are presented in the Table 1. At the end of TP1, 84.6% (44/52) of pts achieved JIA-ACR 30 and 65.4% (34/52) achieved JIA-ACR 70. Clinically relevant reduction of functional ability as assessed by Childhood Health Assessment Questionnaire (CHAQ) also occurred (see Table 1). Table 1. Resolution of axial and peripheral disease symptoms and JIA ACR responses at the end of TP1 and 2 Clinical response, mean (SD) change from BL (unless otherwise stated ) TP1-Wk 12 End of TP2* SEC (N=52 ) SEC (N=22 ) PBO (N=22 ) JSpADA index −2.4 (1.7) −2.7 (1.7) −2.3 (2.1) JSpADA Schöber, % 58.3 100.0 100.0 Inflammatory back pain, % 77.8 100.0 50.0 FABER test, % 52.6 100.0 83.3 Clinical sacroiliitis, % 53.3 100.0 50.0 Enthesitis −2.2 (1.9) −2.5 (2.1) −1.3 (1.8) Dactylitis −0.2 (0.8) −0.2 (1) −0.1 (0.4) JIA ACR30, % 84.6 90.9 68.2 JIA ACR50, % 78.8 81.8 68.2 JIA ACR70, % 65.4 68.2 54.5 JIA ACR90, % 32.7 45.5 50.0 JIA ACR100, % 26.9 36.4 45.5 Inactive disease, % 38.5 50.0 50.0 CHAQ −0.5 (0.5) −0.6 (0.7) −0.4 (0.5) CRP, median (SD) change from BL −1.8 (38.7) −5.8 (38.3) 0 (35.9) JADAS-27 −9.6 (7.5) −11.0 (8.9) −7.6 (8.9) Resolution of enthesitis # , % 72.3 78.6 83.3 Resolution of dactylitis # , % 50 66.7 0 *End of TP2 is based on individual pts’ last visit at TP2. # At BL, in TP1, enthesitis (n= 46); dactylitis (n=5). In TP2, no. of pts who had presence at BL and showed complete resolution at the end of TP2: enthesitis, SEC 14, PBO 18; dactylitis, SEC 3, PBO, 0. CRP, C-reactive protein Conclusion In pts with ERA, SEC demonstrated longer time to disease flare vs PBO and exhibited rapid and sustained improvement of axial and peripheral manifestations up to Wk 104. References [1]Pagnini I, et al. Front Med 2021;8:6673052. [2]Brunner H, et al. Arthritis Rheumatol 2021;73 (suppl 10). [3]Weiss PF, et al. Arthritis Care Res 2014;66:1775-82. Disclosure of Interests Nicolino Ruperto Speakers bureau: Eli Lilly, GlaxoSmith and Kline, Pfizer, SOBI and UCB, Paid instructor for: Eli Lilly and Pfizer, Consultant of: Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celegene, Domain therapeutic, Eli Lilly, EMD Serono, GlaxoSmith and Kline, Idorsia, Janssen, Novartis, Pfizer, SOBI and UCB, Grant/research support from: Bristol Myers and Squibb, Eli Lilly, F Hoffmann-La Roche, Novartis, Pfizer and SOBI, Elena Chertok: None declared, Joke Dehoorne Speakers bureau: Abbvie, Roche, Consultant of: Abbvie, Roche, Pfizer, Grant/research support from: Abbvie, Roche, Gerd Horneff Speakers bureau: Novartis, Pfizer, Janssen, Grant/research support from: Pfizer, Novartis, Roche, MSD, Tilmann Kallinich Speakers bureau: Roche, Ingrid Louw Speakers bureau: Pfizer, Abbvie, BMS, Consultant of: Pfizer, Abbvie, Janssen, Amgen and Cipla, Sandrine Compeyrot-Lacassagne: None declared, Bernard Lauwerys Employee of: UCB Pharma, Neil Martin: None declared, Katherine Marzan Grant/research support from: Novartis, Sanofi, William Knibbe Speakers bureau: Novartis, Amgen, UCB, Abbvie, Ruvie Martin Shareholder of: Novartis, Employee of: Novartis, Xuan Zhu Shareholder of: Novartis, Employee of: Novartis, sarah whelan Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Alberto Martini Speakers bureau: Aurinia, Bristol Myers and Squibb, Eli Lilly, EMD, Janssen, Pfizer, Roche and Serono, Consultant of: Aurinia, Bristol Myers and Squibb, Eli Lilly and EMD, Daniel J Lovell Consultant of: Astra Zeneca, Boehringer Ingelheim, GSK, Hoffman LaRoche, Novartis, UBC, Grant/research support from: Astra Zeneca, Boehringer Ingelheim, GSK, Hoffman LaRoche, Novartis, UBC, Hermine Brunner Consultant of: Novartis, Grant/research support from: Novartis