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BackgroundEnthesitis-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.2ObjectivesTo evaluate the rate of flare risk reduction and efficacy of SEC on axial and peripheral manifestations in patients (pts) with active ERA.MethodsERA pts (2 to 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.ResultsA 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 2Clinical response, mean (SD) change from BL (unless otherwise stated)TP1-Wk 12End 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, %58.3100.0100.0Inflammatory back pain, %77.8100.050.0FABER test, %52.6100.083.3Clinical sacroiliitis, %53.3100.050.0Enthesitis−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, %84.690.968.2JIA ACR50, %78.881.868.2JIA ACR70, %65.468.254.5JIA ACR90, %32.745.550.0JIA ACR100, %26.936.445.5Inactive disease, %38.550.050.0CHAQ−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#, %72.378.683.3Resolution of dactylitis#, %5066.70*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 proteinConclusionIn 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 InterestsNicolino 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

BackgroundChildren with chronic non-infectious uveitis (NIU) are at risk for sight-threatening complications. Methotrexate (MTX) is the preferred first-line systemic treatment. Initial therapeutic response takes 3-6 months to achieve NIU control, leading to prolonged glucocorticoid use. Moreover, at least 50-70% of children fail to fully respond and may accrue ocular damage while awaiting MTX response.ObjectivesTo identify features of children with NIU that are associated with MTX failure.MethodsWe included children who started MTX monotherapy for NIU. We collected demographics, NIU features (type, location, & complications), ANA status, and clinical examination. We characterized children as MTX responders or non-responders. MTX responders are those whose NIU was controlled, defined by: 1) inactive graded by SUN criteria, 2) absence of new or worsening complications, and 3) requirement for ≤2 drops of prednisolone acetate and no oral glucocorticoids.ResultsOf 47 NIU children, 68% were MTX non-responders (Table 1), having a longer duration of NIU (Odds Ratio [OR]=1.28, [CI=1.03-1.8], p =0.023) and developing more ocular complications (OR=1.95 [CI=1.23-3.38], p=0.017), (ROC Area Under the Curve = 0.85). MTX non-responders were more likely to have anterior and/or posterior synechiae (p = 0.001), cataracts (p=0.015), and ocular hypertension (p=0.039). Treatment included adalimumab: 27, infliximab: 14, tocilizumab: 5, golimumab: 4, etanercept: 3, and abatacept: 2.Table 1.Comparison of children with NIU based on MTX response.Responders n=15Non-responders n=32Caucasian14 (93)27 (84)Hispanic or Latino0 (0)3 (9)Female12 (80)23 (72)Age of NIU onset, yrs, median (IQR)4.3 (2.9 – 12.3)4.6 (2.8 - 7.0)Duration of NIU, yrs, median, (IQR)4.1 (2.6 – 5.3)8.2 (4.7 - 11.3)JIA-NIU10 (67)25 (78)Idiopathic CAU2 (13)3 (9)Other3 (20)4 (12)Bilateral disease12 (80)23 (72)Anterior12 (86)29 (91)Presenting BCVA (LogMAR) worst eye, median (IQR)0.2 (0.1 – 0.3)0.1 (0.0 - 0.2)Average # of total complications/person, median (IQR)1 (0 – 2)2.5 (1.0 – 5.5)ANA positive10 (67)26 (81)Earliest ESR8 (6– 18)12 (8 - 18)Earliest Vitamin D32 (26 – 35)31 (23 - 35)Time on MTX, months, median (IQR)35 (19 - 64)19 (7 - 74)Time from systemic or NIU onset to MTX, yrs, median (IQR)0.3 (0.1 – 0.5)0.2 (0.0 - 0.8)MTX PO6 (40)19 (59)MTX SC13 (87)31 (97)We performed a sub analysis of children with idiopathic chronic anterior NIU (CAU) and JIA-associated NIU that included children who failed MTX due to intolerance/toxicity (Figure 1). Using Cox proportional hazard regression, 8 idiopathic CAU failed MTX earlier than 38 JIA-associated NIU (HR 2.77, [CI-=1.06-7.27], p=0.039). Results were similar with the inclusion of other types of NIU (p=0.088) (e.g., HLA-B27, non-anterior idiopathic or with systemic disease).Figure 1.Kaplan-Meier curve showing freedom from TNFi (mos) stratified by diagnosisConclusionTwo out of three children with NIU fail initial MTX monotherapy, exposing them to increased accrual of ocular complications prior to biologic starts. The risk for delay in starting tumor necrosis factor α inhibitors (TNFi) seems higher with CAU. Future studies will examine risk factors that predict MTX response in NIU.References[1]McCracken C, Angeles-Han ST, et.al. Timing of infliximab and adalimumab initiation despite methotrexate in children with chronic non-infectious anterior uveitis. Eye (Lond). 2019;33(4):629-39.[2]Henderson LA, Angeles-Han ST, et.al., Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. Pediatr Rheumatol Online J. 2016;14(1):9.[3]Cooper A, et.al., Failure of methotrexate monotherapy and subsequent response to tumor necrosis factor inhibitors in pediatric non-infectious uveitis (abstract). Arthritis Rheumatol. 2020:72 (suppl 4).Disclosure of InterestsSheila Angeles-Han: None declared, Amy Cassedy: None declared, Theresa Hennard: None declared, Mekibib Altaye: None declared, Hermine Brunner Consultant of: Dr. Brunner’s affiliation Cincinnati Children’s Hospital Medical Center has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer Inc, Takeda, and UBC for the work of Dr. Brunner. Dr. Brunner is a DSMB member for Janssen Pharmaceutical’s trial of ustekinumab pediatric Crohn and Ulcerative colitis., Grant/research support from: Dr. Brunner’s affiliation Cincinnati Children’s Hospital Medical Center has received research grants from BMS, Janssen, Novartis, Pfizer Inc, Roche, and UBC., Eniolami Dosunmu: None declared, Alexei Grom: None declared, Michael Henrickson: None declared, Jennifer Huggins: None declared, Sarah Lopper: None declared, Daniel J Lovell Consultant of: AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer Inc, Takeda, and UBC, Grant/research support from: BMS, Janssen, Novartis, Pfizer Inc, Roche, and UBC, Robert Sisk Consultant of: AGTC, Gyroscope, and Leica, Tracy Ting: None declared, Adam Kaufman Consultant of: Consultant for Alcon, Bausch & Lomb, and 1800contacts, not related or relevant to study content., Virginia Utz: None declared

BackgroundFor children with polyarticular juvenile idiopathic arthritis (pJIA) and inadequate response or intolerance to initial treatment with MTX, treatment options include abatacept.1 Abatacept, a selective T-cell co-stimulation modulator, has a distinct mechanism of action from other current treatments for rheumatic diseases,2 and factors predicting clinical response can help determine optimal treatment strategy. Two phase 3 studies demonstrated the efficacy and safety of IV and SC abatacept in patients with pJIA and an inadequate response to other DMARDs.2,3ObjectivesTo determine baseline and post-baseline factors that may predict a clinical response in children and adolescents with pJIA treated with abatacept for 2 years.MethodsBaseline demographic and disease characteristics and post-baseline factors (50% and 70% improvement in ACR criteria [ACR50, ACR70] at days 57 and 85) were analyzed using data from 2 phase 3 studies of abatacept in patients with JIA aged 2–17 years (SC administration) and 6–17 years (IV administration). Efficacy endpoints were Juvenile Arthritis Disease Activity Score in 10 joints based on CRP (JADAS10-CRP) inactive disease (ID; score of ≤ 2.7),4 and remission, defined as 6 consecutive months of post-baseline JADAS10-CRP ID. Data were analyzed over the entire 2-year study period. The earliest time point at which patients achieved these outcomes was reported. The aforementioned study factors were subjected to a time-to-event analysis, including Cox proportional hazards univariate regression analysis and Cox proportional hazards multivariate regression analysis using stepwise regression; results of the multivariate analysis are reported. Kaplan–Meier analysis was used to estimate time to achieve clinical response. Receiver operating characteristic curves were used to determine threshold values for continuous variables.ResultsOverall, 347 patients were included in the analysis (SC, n = 219; IV, n = 128; 73.8% female; mean [SD] age, 11.3 [4.0] years). Following abatacept treatment, both time to JADAS10-CRP ID and time to JADAS10-CRP remission were predicted (nominal P ≤ 0.05) by age (≤ 11 years: hazard ratio [HR], 1.52 [95% CI, 1.14–2.02] and ≤ 10 years: HR, 1.73 [95% CI, 1.20–2.48], respectively), high-sensitivity CRP (hsCRP; ≤ 0.6 mg/dL: HR, 1.67 [95% CI, 1.22–2.28] and ≤ 0.21 mg/dL: HR, 1.67 [95% CI, 1.15–2.42], respectively), Parent/Patient Global Assessment of well-being (≤ 35.86: HR, 1.88 [95% CI, 1.41–2.51] and ≤ 43.16: HR, 2.05 [95% CI, 1.35–3.10], respectively), and Childhood HAQ-DI (CHAQ-DI; ≤ 1.63: HR, 2.23 [95% CI, 1.47–3.39] and ≤ 0.75: HR, 1.84 [95% CI, 1.24–2.73], respectively) (remission data shown in Figure 1). Disease duration ≤ 2 years from baseline (HR, 1.66 [95% CI, 1.25–2.21]) and SC route of administration (HR, 2.05 [95% CI, 1.45–2.91]) also predicted ID. Among the post-baseline factors, ACR50 at days 57 and 85 predicted both ID (HR, 1.57 [95% CI, 1.04–2.36] and HR, 1.88 [95% CI, 1.41–2.51], respectively) and remission (HR, 1.96 [95% CI, 1.11–3.45] and HR, 3.05 [95% CI, 1.47–6.34], respectively); ACR70 at day 57 also predicted ID (data not shown). Patients with predictive factors for age, hsCRP, Parent/Patient Global Assessment of well-being, and CHAQ-DI, and with lower disease activity achieved ID and/or remission earlier than patients with high disease activity.ConclusionWe identified baseline and post-baseline factors that predicted JADAS10-CRP ID and remission in patients with pJIA treated with abatacept for 2 years. Screening of abatacept-treated patients with pJIA for such factors may help predict earlier achievement of ID and/or remission.References[1]Ringold S, et al. Arthritis Rheumatol 2019;71:846–63.[2]Brunner HI, et al. Arthritis Rheumatol 2018;70:1144–54.[3]Ruperto N, et al. Lancet 2008;372:383–91.[4]Trincianti C, et al. Arthritis Rheumatol 2021;73:1966–75.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Writing and editorial assistance were provided by Candice Judith Dcosta, MSc, of Caudex, funded by Bristol Myers Squibb. We would like to acknowledge Mara Becker, Duke Clinical Research Institute, Durham, NC, USA, for her contribution to the study analysis.Disclosure of InterestsNicolino Ruperto Speakers bureau: Honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers Squibb, Cambridge Healthcare Research, Celgene, Domain Therapeutic, Eli Lilly, EMD Serono, GlaxoSmithKline, Idorsia, inMed, Janssen, Novartis, Pfizer, Sobi, UCB, Consultant of: Honoraria for consultancies or speaker bureaus from the following pharmaceutical companies in the past 3 years: 2 Bridge, Amgen, AstraZeneca, Aurinia, Bayer, Brystol Myers Squibb, Cambridge Healthcare Research, Celgene, Domain Therapeutic, Eli Lilly, EMD Serono, GlaxoSmithKline, Idorsia, inMed, Janssen, Novartis, Pfizer, Sobi, UCB, Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, Pfizer, Consultant of: AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Cerocor, Eli Lilly, EMD Serono, F. Hoffmann-La Roche, GlaxoSmithKline, Idorsia, Janssen, Merck, Novartis, R-Pharm, Sanofi, Grant/research support from: The Cincinnati Children’s Hospital, where HIB works as a full-time public employee, has received contributions from the following industries in the past 3 years: Bristol Myers Squibb, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment to third parties, Alberto Berman Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche, Francisco Avila Zapata: None declared, Gerd Horneff Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, Grant/research support from: AbbVie, Chugai, MSD, Novartis, Pfizer, Roche, Linda Wagner-Weiner Grant/research support from: Abbott, Bristol Myers Squibb, Merck, Pfizer, UCB, Alexander Belot Speakers bureau: Chugai, GlaxoSmithKline, Novartis, Roche (punctual scientific intervention), Grant/research support from: Boehringer Ingelheim, Merck (joint research project), Ruben Burgos-Vargas: None declared, Maria Luz Gámir Gámir: None declared, Claudia Goldenstein-Schainberg Speakers bureau: AbbVie, Janssen, Novartis, Consultant of: AbbVie, Janssen, Novartis, Maria T. Terreri: None declared, Margarita Askelson Consultant of: Acerta Pharma, Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Robert Wong Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Alberto Martini Consultant of: AbbVie, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, Pfizer, Daniel J Lovell Consultant of: AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffman LaRoche, Novartis, UBC (all contracts with employer, CCHMC), Grant/research support from: Bristol Myers Squibb, Janssen, Pfizer, Roche (all contracts with employer, CCHMC); NIH grants: NIAMS, NICHD