2209: Efficacy of Secukinumab in Enthesitis-related Arthritis and Juvenile Psoriatic Arthritis Subtypes of Juvenile Idiopathic Arthritis: Results from a Randomized, Phase 3 Study

Hermine Brunner¹, Elena Chertok², Joke Dehoorne³, Gerd Horneff⁴, Tilmann Kallinich⁵, Ingrid Louw⁶, Maria Alessio⁷, Sandrine Compeyrot-Lacassagne⁸, Bernard Lauwerys⁹, Neil Martin¹⁰, Katherine Marzan¹¹, W Patrick Knibbe¹², Ruvie Martin¹³, Xuan Zhu¹⁴, sarah whelan¹⁵, Luminita Pricop¹⁶, Daniel Lovell¹⁷, Alberto Martini¹⁸ and Nicola Ruperto¹⁹, ¹Division of Rheumatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Department of Pediatrics, Cincinnati, OH, ²Voronezh State Medical University, Voronezh, Russia, ³University Hospital Gent, Gent, Belgium, ⁴Pediatrics, Asklepios Klinik Sankt Augustin GmbH, Sankt Augustin, Germany, ⁵Charité - Universitätsmedizin Berlin, Nuremberg, Germany, ⁶Panaroma Medical Centre, Cape Town, South Africa, ⁷Policlinico Federico II di Napoli, Napoli, Italy, ⁸Great Ormond Street Hospital for Children, London, United Kingdom, ⁹Cliniques Universitaires Saint-Luc, Brussels, Belgium, ¹⁰Royal Hospital for Children, Glasgow, Scotland, United Kingdom, ¹¹Children's Hospital Los Angeles, Los Angeles, CA, ¹²St. Luke's Hospital System, Meridian, ID, ¹³Novartis Pharmaceutical Corporation, East Hanover, NJ, ¹⁴Novartis Pharmaceuticals Corporation, Basking Ridge, NJ, ¹⁵Novartis Ireland Ltd, Crumlin, Dublin, Ireland, ¹⁶Novartis Pharmaceuticals Corporation, East Hanover, NJ, ¹⁷Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ¹⁸Istituto Giannina Gaslini, Genova, Italy, ¹⁹IRCCS Istituto Giannina Gaslini; PRINTO, Clinica Pediatrica e Reumatologia, Genova, Italy

Background/Purpose: Juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) represent pediatric counterparts of adult non-radiographic axial spondyloarthritis and psoriatic arthritis, respectively.^1,2 JUNIPERA, a 2-year, randomized, double-blind, placebo (PBO)-controlled trial demonstrated significantly longer time to flare with secukinumab (SEC) vs PBO with sustained improvement of signs and symptoms up to week (wk) 104.³ The effect of SEC on axial and peripheral manifestations in active ERA and JPsA patients (pts) is presented here.

Methods: Pts (2–18 years of age) with active disease (both ≥3 active joints and ≥1 active enthesitis site) were treated with open-label (OL) subcutaneous SEC (75/150 mg in pts < 50/ ≥50 kg) in treatment period (TP) 1. SEC was administered at baseline (BL) and wks 1–4, 8, and 12. Responders at wk 12 (pts who achieved at least JIA-ACR30 response) were randomized into the double-blinded, withdrawal TP2 to continue SEC or PBO every 4 wks until a disease flare or up to wk 100. The time to flare in ERA and JPsA pts in TP2 is reported here. JIA-ACR responses, resolution of enthesitis and dactylitis, Juvenile Arthritis Disease Activity Score (JADAS)-27, and axial, peripheral, and skin manifestations were also assessed.

Results: A total of 52/86 (60.5%) pts with ERA (mean age, 13.7 years; male, 78.8%) and 34/86 (39.5%) pts with JPsA (mean age, 12.2 years; male, 47.1%) were enrolled in the OL TP1. The relative risk reduction of experiencing a disease flare in TP2 in ERA and JPsA pts is provided in Figures 1 and 2, respectively. Improvements in JIA-ACR responses, inactive disease and resolution of enthesitis and dactylitis were observed in ERA and JPsA pts with SEC treatment at wk 12 and at the end of TP2 (Table). Axial symptoms in ERA with SEC and PBO treatment at the end of TP2 were: modified Schober's test, 100% and 100%; inflammatory back pain, 100% and 50%; Flexion, ABduction, External Rotation (FABER) test, 100% and 83.3%; and clinical sacroiliitis, 100% and 50%. Pts who had Childhood Health Assessment Questionnaire score=0 at the end of TP2 with SEC and PBO treatment were 9 each in ERA and 8 each in JPsA. JPsA pts with mild-to-moderate skin psoriasis (7/15; investigator's global assessment [2011 modified version; IGA mod 2011]) at BL showed improvements in overall psoriatic skin manifestations at wk 12 (13/15): clear (n=8, 53.3%) and almost clear (n=5, 33.3%).

Conclusion: In pts with active ERA and JPsA, SEC demonstrated a longer time to disease flare and a reduction of flare risk compared with PBO up to wk 104 and exhibited rapid and sustained improvement of axial, peripheral and skin manifestations.

References
1. Pagnini I, et al. Front Med. 2021;8:6673052.
2. Zisman D, et al. J Rheumatol. 2018;94:11–16.
3. Brunner H, et al. Arthritis Rheumatol. 2021;73 (suppl 10).
Figure 1. Time to disease flare in active ERA patients in Treatment Period 2

Figure 2. Time to disease flare in active JPsA patients in Treatment Period 2

Table. JIA ACR responses and resolution of axial and peripheral disease symptoms at week 12 and at the end of TP2
Disclosures: H. Brunner, Cincinnati Children's Hospital, Pfizer, GlaxoSmithKlein(GSK), AbbVie/Abbott, AstraZeneca, Medimmune, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb(BMS), Celgene, Eli Lilly, EMD Serono, Idorsia, Cerecor, Janssen, Roche, Merck/MSD, Novartis, R-Harm, Sanofi; E. Chertok, None; J. Dehoorne, Abbvie, Roche, Pfizer; G. Horneff, Roche, Pfizer, Novartis, Merck/MSD, Eli Lilly, AbbVie/Abbott; T. Kallinich, Roche; I. Louw, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Pfizer, Janssen, Amgen, Cipla; M. Alessio, None; S. Compeyrot-Lacassagne, None; B. Lauwerys, UCB; N. Martin, None; K. Marzan, Novartis, Sanofi; W. Knibbe, Novartis, Amgen, UCB, AbbVie/Abbott; R. Martin, Novartis; X. Zhu, Novartis; s. whelan, Novartis; L. Pricop, Novartis; D. Lovell, AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKlein(GSK), Novartis, UCB, Bristol-Myers Squibb(BMS), Pfizer, Janssen, NIH/NIAMS, NIH/NICHD, Roche; A. Martini, Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, AbbVie/Abbott, Idorsia; N. Ruperto, 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers and Squibb, Celgene, inMed, Cambridge Healthcare Research, Domain Therapeutic,, EMD Serono, Glaxo Smith Kline, Idorsia, Janssen, Eli Lilly, Novartis, Pfizer, Sobi, UCB.