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Clinical Trial
. 2023 Jan;82(1):154-160.
doi: 10.1136/ard-2022-222849. Epub 2022 Aug 12.

Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial

Hermine I Brunner  1 , Ivan Foeldvari  2 , Ekaterina Alexeeva  3 , Nuray Aktay Ayaz  4 , Inmaculada Calvo Penades  5 , Ozgur Kasapcopur  6 , Vyacheslav G Chasnyk  7 , Markus Hufnagel  8 , Zbigniew Żuber  9 , Grant Schulert  10 , Seza Ozen  11 , Adelina Rakhimyanova  12 , Athimalaipet Ramanan  13   14 , Christiaan Scott  15 , Betul Sozeri  16 , Elena Zholobova  17 , Ruvie Martin  18 , Xuan Zhu  18 , Sarah Whelan  19 , Luminita Pricop  18 , Alberto Martini  20 , Daniel Lovell  21 , Nicolino Ruperto  22 ; Paediatric Rheumatology INternational Trials Organization (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG)
Affiliations
Clinical Trial

Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial

Hermine I Brunner et al. Ann Rheum Dis. 2023 Jan.

Abstract

Background: Treatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy.

Methods: In this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks. Patients who flared in TP2 immediately entered open-label secukinumab TP3 that lasted up to week 104. Primary endpoint was time to disease flare in TP2.

Results: A total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001). Exposure-adjusted incidence rates (per 100 patient-years (PY), 95% CI) for total patients were 290.7/100 PY (230.2 to 362.3) for adverse events and 8.2/100 PY (4.1 to 14.6) for serious adverse events in the overall JIA population.

Conclusions: Secukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis.

Trial registration number: NCT03031782.

Keywords: arthritis, juvenile; arthritis, psoriatic; biological therapy.

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Conflict of interest statement

Competing interests: HIB has received grants and consulting fees from Novartis; ICP has received payment honoria for lectures, presentations, speakers bureaus from Novartis; MH has received payment for participation on data safety monitoring board or advisory board from Novartis;GSS has received grants and consulting fees from Novartis; AVR has received consulting fees from Abbvie, Astra Zeneca, Eli Lilly, Novartis, Roche, UCB; payment/honoria for lectures, presentations, speakers bureaus from Abbvie, Eli Lilly, Novartis, Roche, SOBI; payment for participation on data safety monitoring board or advisory board from Eli Lilly; EZ has received grants or contracts from Novartis and Pfizer; payment/honoria for lectures, presentations, speakers bureaus from Abbvie, MSD, Novartis, Pfizer and Roche; has received support for attending meetings and/or travel from Abbvie, MSD, Novartis, Pfizer and Roche; Ruvie Martin, Xuan Zhu, Sarah Whelan and Luminita Pricop are employees and shareholders of Novartis; AM has received consulting fees from Aurinia, Bristol Myers and Squibb, Eli Lilly, EMD, Serono, Janssen, Pfizer and Roche; payment/ honoria for lectures, presentations, speakers bureaus from Aurinia, Bristol Myers and Squibb, Eli Lilly, EMD, Janssen, Pfizer, Roche and Serono; DJL has received grants and consulting fees from Astra Zeneca, Boehringer Ingelheim, GSK, Hoffman LaRoche, Novartis, and UBC; Nicolino Ruperto has received consulting fees from 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; payment/ honoria for lectures, presentations, speakers bureaus from Eli Lilly, GlaxoSmith and Kline, Pfizer, SOBI and UCB; has received payment for participation on data safety monitoring board or advisory board from Eli Lilly and Pfizer; has received funding from Bristol Myers and Squibb, Eli Lilly, F Hoffmann-La Roche, Novartis, Pfizer and SOBI.

Figures

Figure 1
Figure 1
Time to disease flare in (A) overall JIA population and JIA subcategories of (B) ERA and (C) JPsA in TP2 A) JIA: 72% flare risk reduction; HR, 0.28; 95% CI, 0.13 to 0.63; p<0.001 B) ERA: 55% flare risk reduction; HR, 0.45; 95% CI, 0.16 to 1.28; p=0.075 C) JPsA: 85% flare risk reduction; HR, 0.15; 95% CI, 0.04 to 0.57; p<0.001. HR and associated 95% CIs were based on a Cox proportional hazards model with treatment and analysis factors JIA category (ERA or JPsA) and MTX use at baseline as explanatory variables. Log-rank test was adjusted for analysis factors JIA category (ERA or JPsA) and methotrexate use at baseline. SEC: all patients who did not take any placebo. Placebo in TP2: all patients who took placebo in TP2 and SEC in other period/s. Day 1: date of randomisation. Disease flare was derived relative to the end of TP1 (week 12 visit). Patients who did not experience a disease flare in TP2, were censored at the date of their last non-missing flare evaluation in TP2. Patients at risk: patients in TP2 who did not have flare and were not censored before or at the start of the specified day. ERA, enthesitis-related arthritis; JIA, juvenile idiopathic arthritis; JPsA, juvenile psoriatic arthritis; m/n, proportion of patients with disease flare in TP2; NC, not calculable; SEC, secukinumab; TP, treatment period.
Figure 2
Figure 2
Improvement in ACR responses from baseline with open-label secukinumab in TP1 (A), and improvement from baseline at the end of TP2 (B). *Inactive disease status. 95% CI are from NRI analysis of ACR response derived relative to baseline. N=86 N, number of patients in the full analysis set; n, number of patients with response (B). *Inactive disease status. NRI analysis. ACR, American College of Rheumatology; JIA, juvenile idiopathic arthritis; m, total number of patients with an assessment at the end of TP2; N, total number of patients in the treatment group; n, number of patients who satisfy the criteria; NRI, non-responder imputation; TP, treatment period.
Figure 3
Figure 3
Mean JADAS-27 in TP1 and TP2 in the overall JIA population Full analysis set. MMRM analysis. *Least square mean values. JADAS-27 ranges from 0 to 57 (higher scores indicate more disease activity). HDA, high disease activity; ID, inactive disease; JADAS-27, Juvenile Arthritis Disease Activity Score in 27 joints; JIA, juvenile idiopathic arthritis; MDA, minimal disease activity; MMRM, mixed-effect model repeated measure; MoDA, moderate disease activity; N, total number of patients in the treatment group; TP, treatment period
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References

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