Secukinumab Treatment in Children and Adolescents with Enthesitis-related Arthritis and Juvenile Psoriatic Arthritis: Efficacy and Safety Results from a Phase 3 Study

Hermine Brunner¹, Ivan Foeldvari², Ekaterina Alexeeva³, Nuray Ayaz⁴, Inmaculada Calvo Penads⁵, Ozgur Kasapcopur⁶, Vyacheslav Chasnyk⁷, Markus Hufnagel⁸, Zbigniew Zuber⁹, Grant Schulert¹, Seza Ozen¹⁰, Artem Popov¹¹, Athimalaipet Ramanan¹², Christiaan Scott¹³, Betul Sozeri¹⁴, Elena Zholobova¹⁵, Xuan Zhu¹⁶, Sarah Whelan¹⁷, Luminita Pricop¹⁸, Angelo Ravelli¹⁹, Alberto Martini²⁰, Daniel Lovell²¹ and Nicolino Ruperto²², ¹Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ²Hamburger Zentrum fuer Kinder- und Jugendrheumatologie, Hamburg, Germany, ³Scientific Center of Children Health of RAMS, Moscow, Russia, ⁴Istanbul University, İstanbul, Turkey, ⁵Hospital Universitario y Politécnico La Fe, Valencia, Spain, ⁶Istanbul University-Cerrahpasa, İstanbul, Turkey, ⁷Saint-Petersburg State Pediatric Medical Academy, Saint Petersburg, Russia, ⁸Division of Pediatric Infectious Diseases and Rheumatology, Department of Pediatrics and Adolescent Medicine, University Hospital Medical Center Freiburg, Medical Faculty, University of Freiburg, Freiburg, Germany, ⁹Paediatric Rheumatology International Trials Organisation (PRINTO), Lodz, Poland, ¹⁰Hacettepe University Medical Faculty, Ankara, Turkey, ¹¹Ural State Medical University, Yekaterinburg, Russia, ¹²University of Bristol, Bristol, United Kingdom, ¹³Paediatric Rheumatology, University of Cape Town, Cape Town, South Africa, ¹⁴University of Health Sciences, Umraniye Tranining and Research Hospital Division of Pediatric Rheumatology, Istanbul, Turkey, ¹⁵First Moscow State Medical University n.a. I.M.Sechenov, Moscow, Russia, ¹⁶Novartis Pharmaceuticals Corporation, East Hanover, NJ, ¹⁷Novartis, Dublin, Ireland, ¹⁸Novartis Pharmaceutical Corporation, East Hanover, NJ, ¹⁹Istituto Giannina Gaslini, Genoa, Italy, ²⁰IRCCS Istituto G. Gaslini, Università di Genova Pediatria II, Genova, Italy, ²¹Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH, ²²IRCCS Istituto Giannina Gaslini; PRINTO, Clinica Pediatrica e Reumatologia, Genova, Italy

Meeting: ACR Convergence 2021

Keywords: Biologicals, Juvenile idiopathic arthritis, Pediatric rheumatology, Psoriatic arthritis, spondyloarthritis

Session Information

Date: Monday, November 8, 2021

Title: Plenary III (1424–1429)

Session Type: Plenary Session

Session Time: 10:30AM-10:45AM

Background/Purpose: Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two conditions that represent pediatric correlates of axial spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively.^1,2 Secukinumab (SEC) has demonstrated efficacy and safety in adult patients (pts) with PsA, ankylosing spondylitis and non-radiographic axSpA.^3-5 This study evaluated efficacy and safety of SEC using a randomized double-blind placebo controlled flare prevention design in pts with active ERA and JPsA.

Methods: Pts (aged 2 to < 18 years) classified as ERA or JPsA according to ILAR criteria of ≥ 6 months duration with active disease were included. The 2-year study consisted of open-label (OL) s.c. SEC (75/150 mg in pts < 50/ ≥ 50 kg) treatment at baseline (BL), and at Weeks (Wk) 1, 2, 3, 4, 8 and 12 in treatment-period (TP) 1. Responders who achieved at least JIA ACR 30 response at Wk 12 were randomized into the double-blinded TP2 to continue SEC or placebo (PBO) every four wks until a disease flare, or up to Wk 100. The primary endpoint was the time to flare in TP2; key secondary endpoints included JIA ACR 30/50/70/90/100, inactive disease, juvenile arthritis disease activity score (JADAS), enthesitis and active joint counts, and safety. Analysis of time to flare in TP2 included the proportion of pts with disease flare, Kaplan-Meier estimate of median days for time to flare, hazard ratio estimate, and stratified log-rank test P-value. Intent-to-treat (ITT) analysis using non-responder imputation (NRI) and as observed analysis were performed for JIA ACR 30/50/70/90/100 responses and inactive disease.

Results: 86/97 (88.7%) screened pts were enrolled in TP1 (mean age, 13.1 years; female, 33.7%; ERA, n=52; JPsA, n=34) with a mean JADAS-27 score of 15.1 and enthesitis count of 2.6 at BL. At Wk 12, 75/83 (90.4%) pts achieved JIA ACR 30 and entered TP2. There were 21 flares in PBO treated and 10 flares in SEC treated pts during TP2. The primary endpoint was met as, compared to PBO, SEC treated pts had a significantly longer time to flare, resulting in a 72% reduced flare risk (HR: 0.28; 95% CI: 0.13–0.63; P< 0.001). JIA ACR responses, disease activity, enthesitis count and joints with active arthritis are reported in the Table. There were minor differences between the ITT and as observed analysis in JIA ACR responses and inactive disease in TP1. Improvement in the JADAS-27 score was observed in pts in both the ERA and JPsA categories (Figure). Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in the SEC and PBO groups were comparable in the entire TP. No new safety signals were observed in pts receiving SEC (injection site reaction, n=1; overall pt-years =141.5).

Conclusion: In children and adolescents with ERA and JPsA, efficacy of SEC was demonstrated with a significantly longer time to flare vs PBO with sustained improvement of signs and symptoms up to Wk 104. Efficacy was observed in both ERA and JPsA pts along with a favorable safety profile.

References:

1. Colbert RA. Nat Rev Rheumatol. 2010;6:477–85.

2. Martini A, et al. J Rheumatol. 2019;46:190–7.

3. McInnes IB, et al. Lancet. 2015;386:1137–46.

4. Baeten D, et al. N Engl J Med. 2015;373:2534–48.

5. Deodhar A, et al. Arthritis Rheumatol. 2021;73:110–20.

Efficacy of secukinumab at the end of Treatment Periods 1 and 2 (Key secondary endpoints) as per ITT and NRI imputation for JIA ACR evaluation/inactive disease and as observed for continuous variables

Improvement in JADAS_27 in the overall population, and ERA and JPsA categories in treatment period 1

Disclosures: H. Brunner, Novartis, 6, Pfizer, 6, Roche, 6, GlaxoSmithKline, 6, Abbvie, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Biogen, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, AstraZeneca-Mediimmune, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Boehringer, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, BMS, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Celgene, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Eli Lilly, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, EMD Serono, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Idorsia, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Cerocor, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, F.Hoffman-La Roche, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Merck, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Novartis, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Sanofi, 12, Contributions to employer (Cincinatti Children's Hospital) *NOTE: This funding has been reinvested for the research activities of the hospital in a fully independent manner without any commitment to third parties, Aurina, 2; I. Foeldvari, Novartis, 4; E. Alexeeva, Novartis, 6, Pfizer, 6, Sanofi, 6, MSD, 6, Amgen, 6, Eli Lilly, 6, Roche, 6; N. Ayaz, None; I. Calvo Penads, Sobi, 2, 6, Novartis, 2, 6, Abbvie, 2, 6, GlaxoSmithKline, 2, 6, Pfizer, 2, 6, Amgen, 2, 6, Clementia, 2, 6; O. Kasapcopur, None; V. Chasnyk, Pfizer, 5, Novartis, 5, Amgen, 5, Elli Lilly, 5, Bristol Myers Squibb, 5, GlaxoSmithKline, 5, Roche, 5; M. Hufnagel, None; Z. Zuber, None; G. Schulert, Novartis, 6; S. Ozen, None; A. Popov, None; A. Ramanan, Roche, 6, Sobi, 6, Eli Lilly, 6, UCB, 6, Novartis, 6; C. Scott, None; B. Sozeri, Novartis, 6; E. Zholobova, Abbvie, 6, Pfizer, 6, Roche, 6; X. Zhu, Novartis, 3, 11; S. Whelan, Novartis, 3, 11; L. Pricop, Novartis, 3, 11; A. Ravelli, Abbvie, 2, 6, BMS, 2, 6, Pfizer, 2, 6, Hoffmann-La Roche, 2, 6, Novartis, 2, 6, Centocor, 2, 6, Anjelini Holding, 2, 6, Reckitt Benckiser, 2, 6; A. Martini, Eli Lilly, 2, 6, Janssen, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, Abbvie, 2, 6, EMD Serono, 2, 6; D. Lovell, Bristol Myers Squibb, 12, PI, Abatacept, Juvenile Idiopathic Arthritis, AstraZeneca Pharm, 2, Boehringer Ingleheim, 2, GSK, 2, Hoffman LaRoche, 2, Janssen, 12, Co-PI of overall studies of IV and sub-Q Golimumab in JIA, NIH / NIAMS, 12, R01 AR074098-01A1, NIH / NICHD, 12, NIH / R01 HD 089928-01A1, Novartis, 2, Pfizer, 3, Roche, 12, PI, Tociluzumab, Juvenile Idiopathic Arthritis, UBC, 2; N. Ruperto, Ablynx, 2, 6, Amgen, 2, 6, Astrazeneca-Medimmune, 2, 6, Aurinia, 2, 6, Bayer, 2, 6, Bristol Myers and Squibb, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, Cambridge Healthcare Research (CHR, 2, 6, Celgene, 2, 6, Domain therapeutic, 2, 6, Eli-Lilly, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, EMD Serono, 2, 6, Glaxo Smith and Kline, 2, 6, Idorsia, 2, 6, Janssen, 2, 6, Novartis, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, Pfizer, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, Sobi, 2, 6, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties, UCB, 2, 6, F Hoffmann-La Roche, 12, The IRCCS IGG, where NR works as full-time public employee has received contributions, this has been reinvested for research activities of the hospital in a fully independent manner, without any commitment with third parties.

To cite this abstract in AMA style:

Brunner H, Foeldvari I, Alexeeva E, Ayaz N, Calvo Penads I, Kasapcopur O, Chasnyk V, Hufnagel M, Zuber Z, Schulert G, Ozen S, Popov A, Ramanan A, Scott C, Sozeri B, Zholobova E, Zhu X, Whelan S, Pricop L, Ravelli A, Martini A, Lovell D, Ruperto N. Secukinumab Treatment in Children and Adolescents with Enthesitis-related Arthritis and Juvenile Psoriatic Arthritis: Efficacy and Safety Results from a Phase 3 Study [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/secukinumab-treatment-in-children-and-adolescents-with-enthesitis-related-arthritis-and-juvenile-psoriatic-arthritis-efficacy-and-safety-results-from-a-phase-3-study/. Accessed .

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