OBJECTIVE:To investigate the validity of the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) in children with enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (jPsA) in a prospective clinical trial setting. METHODS:JUNIPERA (ClinicalTrials.gov: NCT03031782) is a phase III, placebo-controlled withdrawal study investigating the safety and efficacy of secukinumab in children with ERA and jPsA. After 12 weeks of open-label treatment with secukinumab, patients were randomized 1:1 to secukinumab or placebo until disease flare or week 52. JSpADA validity was assessed using 3 criteria: convergent validity (Spearman correlation) at week 12 with the Juvenile Arthritis Disease Activity Score in 10 joints (JADAS10), clinical JADAS10 (cJADAS10), and physician global assessment of disease activity (PGA); discriminatory validity at week 12 among patients with active or inactive disease and juvenile idiopathic arthritis American College of Rheumatology response criteria; and responsiveness to change in clinical disease activity from weeks 12 to 52. RESULTS:At week 12, mean (SD) JSpADA scores showed moderate to good correlation with JADAS10, cJADAS10, and PGA scores (all Spearman ρ > 0.4) and were higher among patients with active vs inactive disease (1.8 [1.3] vs 0.5 [0.8], P < 0.001). Patients with improved disease activity from weeks 12 to 52 had greater improvements in JSpADA than patients with worsening disease (-0.8 [1.1] vs 0.4 [1.0], P < 0.001); patients with stable disease had minimal change in JSpADA (-0.1 [0.5]). Validity results were similar for ERA and jPsA. CONCLUSION:These results validate JSpADA as a disease activity measure for children with ERA and jPsA in a prospective clinical trial setting.

The objective of this modeling and simulation analysis was to determine an intravenous (IV) secukinumab dosing regimen with steady‐state exposure within the ranges of the approved subcutaneous (SC) regimens (300 and 150 mg every 4 weeks [q4w]) and to predict the efficacy and safety of this IV regimen for patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA). This approach was suggested by the US Food and Drug Administration (FDA) following review of the primary endpoint analysis results of secukinumab 3 mg/kg q4w IV in patients with PsA (INVIGORATE‐2 study). Noting the higher exposure of the investigated IV regimen compared to the approved SC regimens, the FDA considered that the INVIGORATE‐2 data available through Week 16 only may not convey sufficient safety information to support the benefit–risk assessment of this IV regimen. A population pharmacokinetic (popPK) analysis was conducted on a pool of 15 PsA or axSpA clinical trials to identify 1.75 mg/kg IV secukinumab q4w (with or without a 6 mg/kg IV loading dose at Week 0) as a regimen with steady‐state exposure within the ranges of the approved SC regimens. This entitled its efficacy and safety to be assessed by full extrapolation from those of the approved SC regimens. This extrapolation was substantiated by the use of exposure‐response analyses to predict the efficacy and safety of the IV regimen. Based on those analyses, this IV secukinumab regimen, not tested in clinical trials, was approved by the FDA for the treatment of patients with PsA and axSpA.

ObjectiveThe aim of this study was to evaluate the efficacy and safety of intravenous (IV) secukinumab in patients with active psoriatic arthritis (PsA). MethodsINVIGORATE-2 (NCT04209205) was a randomized, placebo-controlled, phase 3 trial. Patients with active PsA were randomized 1:1 to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks [q4w]) or placebo. At week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg q4w), and patients who received IV secukinumab continued treatment through week 52. The primary efficacy endpoint was achievement of 50% improvement in American College of Rheumatology response criteria (ACR50) at week 16. Efficacy and safety were evaluated through weeks 52 and 60, respectively. ResultsAmong 191 patients randomized to IV secukinumab and 190 to placebo/IV secukinumab, 177 (92.7%) and 170 (89.5%) completed the entire study period, respectively. A significantly higher proportion of patients who received IV secukinumab versus placebo achieved ACR50 at week 16 (31.4% vs 6.3%; adjusted P < 0.0001). All secondary efficacy endpoints were met at week 16 (all adjusted P < 0.05 using the predefined hypothesis-testing hierarchy). Patients who switched from placebo to secukinumab at week 16 showed rapid improvements in ACR50 rates; by week 52, both treatment arms experienced similar improvements in efficacy outcomes. No new or unexpected safety signals were observed with receiving IV secukinumab. One death was reported in the placebo group before week 16. ConclusionIV secukinumab led to rapid and sustained improvements in clinical measures of PsA, and the safety profile was consistent with that of secukinumab administered subcutaneously.

Introduction: The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2-5 studies in patients with psoriatic arthritis (PsA). Methods: Data were pooled from US patients enrolled in the phase 3 FUTURE 2-5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350). Patients received secukinumab 300 or 150 mg with subcutaneous loading dose, secukinumab 150 mg without subcutaneous loading dose, or placebo. Categorical efficacy and health-related quality-of-life (QoL) outcomes and safety were evaluated at week 16. Subgroup analyses were performed based on tumor necrosis factor inhibitor (TNFi) status and body mass index (BMI). For hypothesis generation, odds ratios (ORs) for American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment were estimated using logistic regression without adjustment for multiple comparisons. Results: Of 2148 international patients originally randomized, 279 US patients were included in this pooled analysis. Mean BMI was > 30 kg/m(2) and 55.2% had prior TNFi treatment. ORs for ACR20/50/70 significantly favored patients receiving secukinumab 300 mg and 150 mg with loading dose vs. placebo (P < 0.05), but not those receiving secukinumab 150 mg without loading dose vs. placebo. For PASI75, ORs favored all secukinumab groups over placebo (P < 0.05); for PASI90 and PASI100, only the secukinumab 300-mg group was significantly favored over placebo (P < 0.05). Conclusions: In this challenging sub-population of US patients with PsA, secukinumab provided rapid improvements in disease activity and QoL. Patients with PsA and active psoriasis might benefit more from secukinumab 300 mg than 150 mg.

Background: Pooled safety data have been reported for secukinumab (SEC) administration in patients with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).[1,2] Objectives: Here, we report safety profile of SEC after extensive patient exposure in clinical trials from a larger pool of patients and including more studies than previously published.[3] Methods: The pooled safety analysis included 47 Phase II/III/IV clinical trials (PsO: 30; PsA: 9; axSpA [including ankylosing spondylitis {AS} and non-radiographic axial spondyloarthritis {nr-axSpA}]: 8 trials) with patients who had received ≥1 dose of subcutaneous SEC 150 mg and/or 300 mg for ≥16 weeks (cut-off: June 2022). Adverse events (AEs) were reported as exposure-adjusted incidence rates (EAIRs)/100 patient-years (PYs). Results: A total of 15,644 patients (PsO [N=9561], PsA [N=3880] and axSpA [N=2203]) were included in the analysis. The most frequent AEs reported across all indications were nasopharyngitis (EAIR [95% confidence interval {CI}]: PsO, 19.44 [18.66, 20.24]; PsA, 11.36 [10.54, 12.23]; axSpA, 12.91 [11.76, 14.14]) and upper respiratory tract infection (EAIR [95% CI]: PsO, 6.14 [5.75, 6.56]; PsA, 8.10 [7.42, 8.82]; axSpA, 8.28 [7.41, 9.22]). EAIRs/100 PYs for inflammatory bowel disease, malignancies and major adverse cardiovascular events remained low across all indications. The EAIRs/100 PYs for AEs of special interest are reported in Table 1. Conclusion: This pooled safety data analysis of 47 Phase II/III/IV clinical trials demonstrates that secukinumab is well tolerated in patients with PsO, PsA and axSpA, and shows no new signals with longer-term follow-up compared to published studies.1,2 REFERENCES: [1] Deodhar A, et al. Arthritis Res Ther. 2019;21:111.[2] Deodhar A, et al. Ann Rheum Dis. 2020;79:722.[3] Gottlieb AB, et al. Acta Derm Venereol. 2022;102:adv00698. Acknowledgements: Medical writing assistance was provided by Ishita Guha Thakurta and Divya Chandrashekhar (Novartis Healthcare Pvt Ltd, Hyderabad) which was funded by Novartis Pharma AG, Basel, Switzerland in accordance with the Good Publication Practice (GPP4) guidelines (http://www.ismpp.org/gpp-2022). Disclosure of Interests: Atul Deodhar Received speaker honoraria from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Received honoraria for consulting from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Received research grants from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Iain B. Mc‎ Innes Received speaker honoraria from AbbVie, Amgen, Bristol Myers Squibb, Cabaletta, Celgene, Compugen, Janssen, Lilly, Moonlake, Novartis, Pfizer, and UCB, Received consultation fees from AbbVie, Amgen, Bristol Myers Squibb, Cabaletta, Celgene, Compugen, Janssen, Lilly, Moonlake, Novartis, Pfizer, and UCB. Board member: Evelo, Received research grant from AbbVie, Amgen, Bristol Myers Squibb, Cabaletta, Celgene, Compugen, Janssen, Lilly, Moonlake, Novartis, Pfizer, and UCB, Xenofon Baraliakos Speaker’s bureau: AbbVie, Bristol Myers Squibb, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant for AbbVie, Bristol Myers Squibb, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Received research grant from AbbVie, Bristol Myers Squibb, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Alice B Gottlieb Honoraria as an advisory board member and consultant for Amgen, Anaptyps Bio, Avotres Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Dice Therapeutics, Eli Lilly, Highlights Therapeutics, Janssen, Novartis, Sanofi, UCB, and Xbiotech, Received research or educational grants from Anaptyps Bio, Highlights Therapeutics, Moonlake Immunotherapeutics AG, Novartis, Bristol Myers Squibb, and UCB Pharma, (all paid to Mount Sinai School of Medicine), Uta Kiltz Received speaker honoraria from AbbVie, Biocad, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Received consultancy honoraria from AbbVie, Biocad, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Received unrestricted grant for research from Abbvie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, and Pfizer, Stefan Schreiber Received consultation fees from AbbVie, Arena, Bristol Myers Squibb, Biogen, Celltrion, Celgene, Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Takeda, and Theravance, Braja Gopal Sahoo Employee of Novartis, Weibin Bao Owns stocks of Novartis, Employee of Novartis, Luminita Pricop Owns stocks of Novartis, Employee of Novartis, Corine Gaillez Owns shares of Novartis and Bristol Myers Squibb, Employee of Novartis, Victor Dong Owns stocks of Novartis, Employee of Novartis, Philip J. Mease Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Consultant for: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Received Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo Bioscience, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB.

Background Secukinumab has demonstrated efficacy and safety in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) categories of juvenile idiopathic arthritis (JIA) for up to 2 years.[1] After completion of a 2-year core study (JUNIPERA), a long-term extension (LTE) study was conducted to evaluate the continued efficacy and safety of secukinumab. Objectives To report interim efficacy and safety results of the LTE study of secukinumab in patients with ERA and JPsA. Methods In the core study, a total of 86 patients (2 to <18 years of age) received secukinumab up to week 12 in the open-label (OL) period.[1] JIA ACR30 responders at week 12 (n=75) were subsequently randomised to secukinumab (n=37) or placebo (n=38) up to week 100 in study period 2. Those who flared after randomisation (secukinumab, n=10; placebo, n=21) received OL secukinumab up to week 100.[1] A total of 54 out of 61 patients who had completed the core study consented to enter the LTE study and received secukinumab (s.c.) (75/150 mg in patients <50/ ≥50 kg) every 4 weeks up to 4 years. Patients whose signs and symptoms were not fully controlled, as judged by the investigator in the LTE, could have dose escalation of their secukinumab dose from 75 mg to 150 mg or 150 mg to 300 mg. Median Juvenile Arthritis Disease Activity Scores (JADAS)-27 were presented up to week 156 for efficacy, and adverse events (AEs) and serious AEs were presented for the entire treatment period up to the cut-off date (maximum up to week 232). Results JADAS-27 in the core study and in the LTE are presented in the Figure 1. A total of 19 patients had dose escalation in the LTE: 8 patients from 75 mg to 150 mg and 11 patients from 150 mg to 300 mg. The overall exposure-adjusted incidence rate per 100 patient-years (PY) of treatment-emergent AEs was 98.4 PY in the entire JIA population. The most commonly reported AEs (preferred term, safety set 5% cut off) were nasopharyngitis (n=9, 16.7%) and arthralgia (n=8, 14.8%). One major adverse cardiovascular event, not related to the study drug, and 2 cases of uveitis were reported. No cases of Crohn’s disease or deaths were reported, and no patient discontinued treatment due to an AE. Conclusion With secukinumab treatment, the JADAS-27 inactive disease status was sustained from week 104 to week 156 in patients with JIA who had completed the 2-year core study and enrolled in the LTE study. Safety data were consistent with adult and paediatric indications, with no new or unexpected safety signals. Reference [1]Brunner HI, et al. Ann Rheum Dis. 2023;82(1):154-160. Acknowledgements The trial was designed jointly by the PRINTO and PRCSG study groups, and Novartis Pharma AG. Disclosure of Interests Nicolino Ruperto Speakers bureau: Ablynx, AstraZeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Consultant of: Ablynx, AstraZeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi, Ivan Foeldvari Consultant of: Novartis, BMF, Bayer, Genentech, Sanofi, Abbvie, Chugai, Medac, BMS, Pfizer, Ekaterina Alexeeva Speakers bureau: Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche, Grant/research support from: Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche, NURAY AKTAY AYAZ: None declared, Grant Schulert Consultant of: Novartis, Grant/research support from: Novartis, Seza Özen: None declared, Artem Popov: None declared, Athimalaipet Ramanan Speakers bureau: Roche, Sobi, Eli Lilly, UCB, Novartis, Christiaan Scott: None declared, Betul Sozeri: None declared, Elena Zholobova Speakers bureau: Abbvie, Pfizer, Roche, Novartis, Grant/research support from: Pfizer, Novartis, Sudhanshu Chakraborty Shareholder of: IQVIA, Employee of: IQVIA, Xuan Zhu Shareholder of: Novartis, Employee of: Novartis, Ruvie Martin Shareholder of: Novartis, Employee of: Novartis, sarah whelan Shareholder of: Novartis, Employee of: Novartis, Sharonjeet Kaur Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Daniel J Lovell Speakers bureau: Abbott, Novartis, Consultant of: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Alberto Martini Speakers bureau: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Consultant of: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Hermine Brunner Speakers bureau: Pfizer, Roche and GlaxoSmithKline, Consultant of: Aurinia, Abbvie, AstraZeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer, Grant/research support from: Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer.

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.

Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was < 0.2/100 patient-years, the incidence of malignancy was ≤ 1/100 patient-years, and the incidence of major adverse cardiovascular events was < 0.7/100 patient-years, with no apparent increases over time. Secukinumab demonstrated a favourable safety profile for up to 5 years of treatment across the 3 indications, and no new safety signals were identified.

Background Psoriatic arthritis (PsA) patient data from two phase 3 secukinumab trials (FUTURE 1, 5) were analysed to quantify the prevalence and extent of pre-existing radiographic damage (RD) at baseline; investigate the association of RD with swollen/tender joint counts (SJC/TJC) at baseline; and investigate the extent to which RD at baseline correlated with response to secukinumab. Methods Pooled data ( N = 1554) provided baseline radiographic bone erosion and joint space narrowing (JSN) scores at pre-specified locations per the van der Heijde-modified total Sharp score (vdH-mTSS) for PsA and swollen and tender joint scores in the same joints at multiple visits. Overall patient RD and individual joints RD bone erosion and JSN scores were assessed. The association between joint activity (tenderness, swelling) and vdH-mTSS was assessed at the overall patient-level and individual joint tender, swollen scores (yes/no) and RD joint JSN and bone erosion scores at the individual joint-level. Treatment response was assessed using SJC/TJC at weeks 16 and 52 and the proportion of patients achieving minimal disease activity (MDA) over all assessments within 1 year from FUTURE 5 alone. Results A substantial prevalence of pre-existing RD with higher prevalence of erosion than JSN was observed (86% and 60% of patients had positive erosion and JSN scores, respectively); higher RD prevalence was associated with longer time since PsA diagnosis. Joint activity was weakly associated with RD at baseline at the patient-level (Pearson’s coefficients: range 0.12–0.18), but strongly associated at the individual joint-level, with a higher probability of tender/swollen joints to associate with higher JSN/erosion scores: all 42 analysed joints showed statistical significance at the 0.05 level (unadjusted) for the relationship between joint tenderness (yes/no) and its JSN score, all but one for tenderness and bone erosion scores, and all but 2 for swollen and JSN scores and for swollen and bone erosion score. Secukinumab (150/300 mg), reduced TJC and SJC across all values of baseline erosion and JSN scores at weeks 16 and 52. Patients with higher levels of RD were less likely to achieve zero tender/zero swollen joint status and had lower chance of achieving MDA. Conclusions PsA patients showed substantial prevalence of RD at baseline that correlated with time since diagnosis, but patient’s individual joint activity was strongly associated with pre-existing RD at those joints. Patients with the highest RD at baseline had a reduced likelihood of achieving zero joint count status.

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

OBJECTIVES:To evaluate the impact of secukinumab on nail psoriasis and other psoriatic disease manifestations in patients with psoriatic arthritis (PsA) with concomitant nail psoriasis from the FUTURE 5 study.METHODS:Eligible patients were randomly allocated to receive subcutaneous secukinumab (300 mg load [300 mg], 150 mg load [150 mg], and 150 mg [no load]) or placebo weekly and then every 4 weeks starting Week 4. Key assessments through Week 104 in this post hoc analysis included modified Nail Psoriasis Severity (mNAPSI), Psoriasis Area and Severity Index (PASI 90), resolution of dactylitis and enthesitis, Dermatology Life Quality Index (DLQI) and radiographic progression (assessed by vdH-mTSS).RESULTS:At baseline, 66.6% patients (663/996) had concomitant nail psoriasis. Baseline characteristics were balanced in the nail subset and comparable with the overall population. Secukinumab reduced mNAPSI score at Week 16 versus placebo: -8.71 (300 mg), -8.95 (150 mg), -7.55 (150 mg no load) versus -2.34 (placebo); all p<0.0001. Mean change from baseline in DLQI at Week 16 was -8.5 (300 mg), -7.4 (150 mg), -7.3 (150 mg no load) versus -2.4 (placebo); all p<0.0001. Overall, the improvements reported at Week 16 sustained through Week 104. The proportion of patients with no radiographic progression (change from baseline in vdH-mTSS≤0.5) at Week 104 was 91.9% (300 mg) 78.9% (150 mg), and 82.4% (150 mg no load).CONCLUSIONS:Secukinumab provided sustained improvements in nail disease, signs and symptoms of PsA, and a low rate of radiographic progression through 2 years in patients with concomitant nail psoriasis.

Secukinumab [an interleukin (IL)‐17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL‐12/23 inhibitor) in patients with moderate‐to‐severe plaque psoriasis.

OBJECTIVES:Peripheral and axial manifestations of psoriatic arthritis (PsA) can lead to irreversible structural damage and chronic disability. Our objective was to explore predictors of radiographic progression and to increase our understanding of treatment effects in subgroups of patients with different rates of structural damage progression.METHODS:We analysed data from two large Phase-3 trials of secukinumab in PsA patients, FUTURE-1 (NCT01392326, n=606) and FUTURE-5 (NCT02404350, n=996), where different posologies ranging from 75 mg to 300 mg were used. We applied a longitudinal Bayesian mixture model with random effects to account for the variability in the repeated radiographic assessments. "Fast progressors" were defined post hoc as patients with a 50% model-estimated probability to progress at least 0.5 mTSS/year faster than an average patient.RESULTS:Higher baseline inflammation and higher body weight were identified as significant predictors of radiographic progression (multivariate model). Model-estimated structural damage progression in an average patient treated with secukinumab 150 mg subcutaneous (s.c.) was slower (0.04 mTSS/year; 95% CI -0.28, 0.34) compared to a patient treated with placebo (0.94 mTSS/year; 95% CI 0.45, 1.45). According to the model, the subgroup of "fast progressors" (hsCRP ≥26 mg/L, body weigth ≥94 kg, inadequate response to prior anti-TNF-alpha, structural damage ≥42 mTSS) treated with secukinumab 150 mg s.c. progressed at 0.56 mTSS/year (95% CI 0.02, 1.09) and 1.46 mTSS/year (95% CI 0.81, 2.11) when treated with placebo.CONCLUSIONS:Greater systemic inflammation and higher body weight at baseline were identified as significant predictors of progression. Even patients with fast radiographic progression could experience a beneficial effect with secukinumab that holds promise to prevent further mobility loss.

Abstract Background/Aims Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two conditions that represent paediatric correlates of axial spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively. Secukinumab has demonstrated efficacy and safety in adult patients with PsA, ankylosing spondylitis, and non-radiographic axSpA. This study evaluated efficacy and safety of secukinumab using a randomized, double-blind, placebo-controlled flare prevention design in patients with active ERA and JPsA. Methods Patients (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 open-label subcutaneous secukinumab (75/150 mg in patients <50/ ≥50 kg) treatment at baseline, and at Weeks 1, 2, 3, 4, 8, and 12 in treatment period (TP) 1. Responders who achieved at least JIA ACR 30 response at Week 12 were randomized into the double-blind TP2 to continue secukinumab or placebo every 4 weeks until disease flare, or up to Week 100. Primary endpoint was 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 proportion of patients with disease flare, Kaplan-Meier estimate of median days for time to flare, hazard ratio (HR) 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 patients 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 baseline. At Week 12, 75/83 (90.4%) patients achieved JIA ACR 30 and entered TP2. There were 21 flares in placebo-treated and 10 flares in secukinumab-treated patients during TP2. Primary endpoint was met: secukinumab-treated patients had significantly longer time to flare versus placebo, resulting in a 72% reduced flare risk (HR: 0.28; 95% CI: 0.13-0.63; P<0.001). There were minor differences between the ITT and as-observed analysis in JIA ACR responses and inactive disease in TP1. Improvement in JADAS-27 score was observed in patients in both ERA and JPsA categories (mean JADAS-27 score of 4.6). Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in secukinumab and placebo groups were comparable in entire TP. No new safety signals were observed in patients receiving secukinumab (injection-site reaction, n = 1; overall patient-years=141.5). Conclusion In children and adolescents with ERA and JPsA, efficacy of secukinumab was demonstrated with significantly longer time to flare versus placebo, with sustained improvement of signs and symptoms up to Week 104. Efficacy was observed in ERA and JPsA patients along with a favorable safety profile. Disclosure A.V. Ramanan: Consultancies; Novartis, Eli Lilly, UCB, Abbvie, Sobi, Roche. Honoraria; Novartis, Eli Lilly, UCB, Abbvie, Sobi, Roche. H.I. Brunner: Consultancies; Aurina, AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer. Member of speakers’ bureau; Pfizer, Roche, GlaxoSmithKline. Grants/research support; Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, Pfizer. I. Foeldvari: Consultancies; Novartis, Eli Lilly, Pfizer. E. Alexeeva: Member of speakers’ bureau; Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche. Grants/research support; Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche. N.A. Ayaz: None. I. Calvo: Consultancies; Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia. Member of speakers’ bureau; Sobi, Novartis, Novartis, GlaxoSmithKline, Pfizer, Amgen, Clementia. O. Kasapcopur: None. V.G. Chasnyk: None. M. Hufnagel: Grants/research support; Astellas, F. Hoffmann-La Roche, Novartis. Z. Zuber: None. G. Schulert: Consultancies; Sobi, Novartis. S. Ozen: None. A. Popov: None. C. Scott: None. B. Sözeri: None. E. Zholobova: Member of speakers’ bureau; Abbvie, Pfizer, Roche, Novartis. Grants/research support; Pfizer, Novartis. X. Zhu: Other; Employee of Novartis. S. Whelan: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. L. Pricop: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Ravelli: Consultancies; AbbVie, Pfizer. Honoraria; AbbVie, Pfizer, Novartis, Reckitt-Benkiser, Angelini. Member of speakers’ bureau; Novartis. Grants/research support; Novartis, Pfizer. A. Martini: Consultancies; Aurinia, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche. Honoraria; Aurinia, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche. D.J. Lovell: Consultancies; AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie. Member of speakers’ bureau; Abbott, Novartis, DSMB member: Forest Research, NIH-NIAMS, Canadian Arthritis Society. N. Ruperto: Honoraria; Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.

Knockoffs provide a general framework for controlling the false discovery rate when performing variable selection. Much of the Knockoffs literature focuses on theoretical challenges and we recognize a need for bringing some of the current ideas into practice. In this paper we propose a sequential algorithm for generating knockoffs when underlying data consists of both continuous and categorical (factor) variables. Further, we present a heuristic multiple knockoffs approach that offers a practical assessment of how robust the knockoff selection process is for a given dataset. We conduct extensive simulations to validate performance of the proposed methodology. Finally, we demonstrate the utility of the methods on a large clinical data pool of more than 2000 patients with psoriatic arthritis evaluated in four clinical trials with an IL-17A inhibitor, secukinumab (Cosentyx), where we determine prognostic factors of a well established clinical outcome. The analyses presented in this paper could provide a wide range of applications to commonly encountered datasets in medical practice and other fields where variable selection is of particular interest.