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OBJECTIVE To document the need for additional Food and Drug Administration (FDA)-approved medications for the treatment of juvenile idiopathic arthritis (JIA). METHODS The electronic medical records of JIA patients treated at Cincinnati Children's Hospital Medical Center (CCHMC) and data from JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry were included in this study. Unmet medication need was defined in 2 ways: (a) the presence of chronically uncontrolled JIA, defined as a physician global assessment of JIA activity ≥3 (on a 0-10 scale, where 0 = inactive) OR ≥3 joints with active arthritis OR a patient global assessment of well-being ≥3 (on a 0-10 scale, where 0 = very well), despite sequential use of ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs); and (b) the use of ≥1 bDMARD not approved for any JIA category. RESULTS At CCHMC, 829 of 1,599 JIA patients (52%) were treated with ≥1 bDMARD, and 304 (19%) had been exposed to ≥1 unapproved bDMARD. In the CARRA Registry, 4,766 of 7,379 children (65%) had received ≥1 bDMARD, and 1,122 (15%) had been prescribed ≥1 unapproved bDMARD. Of those children treated with ≥2 bDMARDs for whom complete data were available, 52% (255 of 487) at CCHMC and 45% (527 of 1,159) in the CARRA Registry had chronically uncontrolled JIA despite the use of ≥2 bDMARDs. CONCLUSION Despite the availability of bDMARDs currently approved for JIA, there is persistent need for additional therapies to control JIA signs and symptoms. Since FDA approval is critical to ensure access to bDMARDs, the study and licensing of new medications is critical to address the unmet medication need and to further improve JIA outcomes.

Objective To evaluate safety and effectiveness of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (JIA) in the STRIVE registry. Methods STRIVE enrolled patients with polyarticular-course JIA into 2 arms based on treatment with methotrexate (MTX) alone or ADA with/without MTX (ADA +/- MTX). Adverse events (AEs) per 100 patient-years of observation time were analyzed by registry arm. Patients who entered the registry within 4 weeks of starting MTX or ADA +/- MTX, defined as new users, were evaluated for change in disease activity assessed by the 27-joint Juvenile Arthritis Disease Activity Score with the C-reactive protein level (JADAS-27(CRP)). Results At the 7-year cutoff date (June 1, 2016), data from 838 patients were available (MTX arm n = 301, ADA +/- MTX arm n = 537). The most common AEs were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%) in the MTX arm and arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (3.0% each) in the ADA +/- MTX arm. Rates of serious infection were 1.5 events/100 patient-years in the MTX arm and 2.0 events/100 patient-years in the ADA +/- MTX arm. AE and serious AE rates were similar in patients receiving ADA with versus without MTX. No deaths or malignancies were reported. New users in the ADA +/- MTX arm showed a trend toward lower mean JADAS-27(CRP)compared with new users in the MTX arm in the first year of STRIVE. Conclusion The STRIVE registry 7-year interim results support the idea that ADA +/- MTX is well tolerated by most children. Registry median ADA exposure was 2.47 (interquartile range 1.0-3.6) years, with 42% of patients continuing ADA at the 7-year cutoff date.

BACKGROUND. Undifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments. METHODS. Sixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing. RESULTS. Thirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS. CONCLUSIONS. In patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression. Fil: de Jesus, Adriana A.. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Hou, Yangfeng. Shandong University; China Fil: Brooks, Stephen. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos Fil: Malle, Louise. cahn School of Medicine at Mount Sinai; Estados Unidos Fil: Biancotto, Angelique. No especifíca; Fil: Huang, Yan. National Institute Of Allergy And Infectious Diseases; Estados Unidos Fil: Calvo, Katherine R.. National Institutes of Health; Estados Unidos Fil: Marrero, Bernadette. No especifíca; Fil: Moir, Susan. No especifíca; Fil: Oler, Andrew J.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos Fil: Deng, Zuoming. National Institute Of Arthritis And Musculoskeletal And Skin Diseases; Estados Unidos Fil: Montealegre Sanchez, Gina A.. National Institute Of Allergy And Infectious Diseases ; Estados Unidos Fil: Ahmed, Amina. No especifíca; Fil: Allenspach, Eric. Washington State University; Estados Unidos Fil: Arabshahi, Bita. Virginia Commonwealth University; Estados Unidos Fil: Behrens, Edward. University of Pennsylvania; Estados Unidos Fil: Benseler, Susanne. University of Calgary; Canadá Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bout Tabaku, Sharon. No especifíca; Fil: Brescia, AnneMarie C.. No especifíca; Fil: Brown, Diane. No especifíca; Fil: Burnham, Jon M.. University of Pennsylvania; Estados Unidos Fil: Caldirola, Maria Soledad. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Carrasco, Ruy. No especifíca; Fil: Chan, Alice Y.. University of California; Estados Unidos Fil: Cimaz, Rolando. Università degli Studi di Milano; Italia Fil: Dancey, Paul. Janeway Children's Hospital And Rehabilitation Centre; Canadá Fil: Dare, Jason. University of Arkansas for Medical Sciences; Estados Unidos Fil: DeGuzman, Marietta. Baylor College Of Medicine; Estados Unidos Fil: Dimitriades, Victoria. No especifíca; Fil: Ferguson, Ian. University of Yale. School of Medicine; Estados Unidos Fil: Ferguson, Polly. University of Iowa; Estados Unidos Fil: Finn, Laura. University of Washington; Estados Unidos Fil: Gattorno, Marco. No especifíca; Fil: Grom, Alexei A.. No especifíca; Fil: Hanson, Eric P.. No especifíca; Fil: Hashkes, Philip J.. No especifíca; Fil: Hedrich, Christian M.. University of Liverpool; Reino Unido Fil: Herzog, Ronit. University of New York; Estados Unidos Fil: Horneff, Gerd. Universitat zu Köln; Alemania Fil: Jerath, Rita. Augusta University; Estados Unidos Fil: Kessler, Elizabeth. University of Missouri; Estados Unidos Fil: Kim, Hanna. No especifíca; Fil: Kingsbury, Daniel J.. No especifíca; Fil: Laxer, Ronald M.. University Of Toronto. Hospital For Sick Children; Canadá Fil: Lee, Pui Y.. Children's Hospital Boston; Estados Unidos Fil: Lee Kirsch, Min Ae. Technische Universität Dresden; Alemania Fil: Lewandowski, Laura. No especifíca; Fil: Li, Suzanne. Hackensack University Medical Center; Estados Unidos Fil: Lilleby, Vibke. Oslo University Hospital; Noruega Fil: Mammadova, Vafa. Azerbaijan Medical University; Azerbaiyán Fil: Moorthy, Lakshmi N.. Robert Wood Johnson Medical School; Estados Unidos Fil: Nasrullayeva, Gulnara. Azerbaijan Medical University; Azerbaiyán Fil: O'Neil, Kathleen M.. Riley Hospital for Children; Estados Unidos Fil: Onel, Karen. Hospital for Special Surgery; Estados Unidos Fil: Ozen, Seza. Hacettepe University; Turquía Fil: Pan, Nancy. Hospital for Special Surgery; Estados Unidos Fil: Pillet, Pascal. Children Hospital Pellegrin-Enfants; Francia Fil: Piotto, Daniela G.P.. Universidade Federal de Sao Paulo; Brasil Fil: Punaro, Marilynn G.. University of Texas; Estados Unidos Fil: Reiff, Andreas. University of Nebraska; Estados Unidos Fil: Reinhardt, Adam. University of Nebraska; Estados Unidos Fil: Rider, Lisa G.. No especifíca; Fil: Rivas Chacon, Rafael. Nicklaus Children’s Hospital; Estados Unidos Fil: Ronis, Tova. Children’s National Health System; Estados Unidos Fil: Rösen Wolff, Angela. Technische Universität Dresden; Alemania Fil: Roth, Johannes. Children’s Hospital of Eastern Ontario; Canadá Fil: Mckerran Ruth, Natasha. Medical University of South Carolina; Estados Unidos Fil: Rygg, Marite. Norwegian University of Science and Technology; Noruega Fil: Schmeling, Heinrike. University of Calgary; Canadá Fil: Schulert, Grant. Children’s Hospital Medical Center; Estados Unidos Fil: Scott, Christiaan. University of Cape Town; Sudáfrica Fil: Seminario, Gisella. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Shulman, Andrew. University of California at Irvine; Estados Unidos Fil: Sivaraman, Vidya. Nationwide Children’s Hospital; Estados Unidos Fil: Son, Mary Beth. Boston Children’s Hospital; Estados Unidos Fil: Stepanovskiy, Yuriy. Shupyk National Medical Academy for Postgraduate Education; Ucrania Fil: Stringer, Elizabeth. Dalhousie University Halifax; Canadá Fil: Taber, Sara. Hospital for Special Surgery; Estados Unidos Fil: Terreri, Maria Teresa. Universidade Federal de Sao Paulo; Brasil Fil: Tifft, Cynthia. No especifíca; Fil: Torgerson, Troy. University of Washington; Estados Unidos Fil: Tosi, Laura. Children’s National Health System; Estados Unidos Fil: van Royen Kerkhof, Annet. Wilhelmina Children’s Hospital Utrech; Países Bajos Fil: Wampler Muskardin, Theresa. New York University School of Medicine; Estados Unidos Fil: Canna, Scott W.. University of Pittsburgh; Estados Unidos Fil: Goldbach Mansky, Raphaela. National Institute Of Allergy And Infectious Diseases ; Estados Unidos

Background:The calcium-binding proteins S100A8/A9 (calprotectin) and S100A12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) are involved in multiple signalling pathways to mediate inflammation, can be secreted by activated monocytes/macrophages and exhibit cytokine-like extracellular functions. Circulating levels of these proteins have been associated with disease and clinical responses in systemic juvenile idiopathic arthritis (sJIA), including treatment response.1 Studies suggest that serum S100A8/A9 and S100A12, which are released at inflammation sites, are more specific biomarkers of local inflammation (e.g. in the synovium) than systemic biomarkers such as CRP and ESR.2,3Objectives:To investigate if baseline S100A8/A9 and S100A12 predict clinical response to abatacept treatment in polyarticular JIA (pJIA), and to assess whether changes from baseline in S100A8/A9 or S100A12 can be better prognostic markers for response to abatacept treatment than CRP in pJIA.Methods:Data are from a phase III trial of SC abatacept for the treatment of pJIA (NCT01844518).4 This 24-month, single-arm, open-label, international, multicentre, two-part study included male and female patients with pJIA aged 2–17 years. This analysis examined the correlation between biomarkers (S100A8/A9, S100A12 and high-sensitivity CRP [hsCRP]) and disease activity (measured using Juvenile Arthritis Disease Activity Score [JADAS]) at baseline, baseline biomarker values as predictors of future treatment response (ACR and JADAS endpoints), and the correlation between change from baseline in biomarker values and treatment response at Day 113.Results:Of 219 total patients, 158 (72%) had S100A8/A9 values and 155 (71%) had S100A12 values at baseline. Median S100A8/A9 and S100A12 values were 3295 ng/mL (normal range, 716–3004 ng/mL) and 176 ng/mL (normal range, 32–385 ng/mL), respectively. S100A8/A9, S100A12 and hsCRP (median 0.20 mg/dL; normal ≤0.6 mg/dL) had a low-to-moderate but significant association with disease activity at baseline; coefficients for associations between JADAS71-CRP low disease activity (LDA) and the biomarkers S100A8/A9, S100A12 and hsCRP were 0.23 (p=0.0038), 0.16 (p=0.0448) and 0.26 (p=0.0001), respectively. Baseline S100A8/A9 level above the median was associated with lower odds of ACR100 at Day 113 (p=0.0052). Figure 1 shows the associations of baseline biomarker values with Day 113 ACR and JADAS scores in the overall population. Baseline S100A8/A9 or S100A12 did not significantly influence ACR50 or ACR70 responses at Day 113, but high baseline values were associated with reduced odds of ACR90 (p=0.01), ACR100 (p=0.005), ACR-inactive disease (ID) (p=0.0001), and JADAS71-CRP (LDA) (p=0.02). By Day 477, elevated baseline S100A12 was still significantly associated with lower odds of ACR100 overall (0.467; p=0.0248) but baseline S100A8/A9 was not; at Day 645, neither was significantly associated with ACR100 response. At Day 113, changes from baseline in S100A8/A9 and S100A12 were correlated with ACR100 (coefficients of 0.22 [p=0.0082] and 0.26 [p=0.0015], respectively) and with ACR-ID (0.22 [p=0.0067] and 0.26 [p=0.0014], respectively); change in hsCRP was not significantly correlated with disease response.Conclusion:S100A8/A9 and S100A12 may serve as prognostic biomarkers to predict response to abatacept treatment at Day 113. Changes from baseline S100A8/A9 and S100A12 levels were more highly correlated with efficacy outcomes including ACR100 and ACR-ID at Day 113 compared with hsCRP.References:[1]Aljaberi N, et al. Pediatr Rheumatol Online J 2020;18:7.[2]Hammer H, et al. Arthritis Res Ther 2011;13:R178.[3]Nordal HH, et al. BMC Musculoskelet Disord 2014;15:335.[4]Brunner H, et al. Arthritis Rheumatol 2018;70:1144–1154.Acknowledgements:Professional medical writing and editorial assistance was provided by Rob Coover, MPH, at Caudex and was funded by Bristol Myers Squibb.Disclosure of Interests:Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Consultant of: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions (>10.000 USD each) from the following industries in the last 3 years: Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Grant Schulert Speakers bureau: Novartis, Consultant of: SOBI, Alyssa Sproles: None declared, Sherry Thornton: None declared, Gabriel Vega Cornejo Speakers bureau: AbbVie, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Janssen, Parexel, Sanofi, Jordi Anton Speakers bureau: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Consultant of: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Grant/research support from: AbbVie, Amgen, Gebro, GlaxoSmithKline, Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, Ruben Cuttica Speakers bureau: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Paid instructor for: AbbVie, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Michael Henrickson: None declared, Ivan Foeldvari Consultant of: Bristol Myers Squibb, Gilead, Hexal, MEDAC, Novartis, Pfizer, Sanofi, Daniel Kingsbury Consultant of: Pfizer, Margarita Askelson Consultant of: Currently working for Syneos Health providing services to Bristol Myers Squibb, Jinqi Liu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sumanta Mukherjee Shareholder of: Bristol Myers Squibb, GlaxoSmithKline, Employee of: Bristol Myers Squibb, GlaxoSmithKline, Robert Wong Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Daniel J Lovell Speakers bureau: Genentech, Wyeth Pharm, Consultant of: Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Regeneron, Takeda, UBC, Wyeth Pharma, Xoma, Alberto Martini Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, Pfizer, Alexei Grom Consultant of: AB2Bio, Novartis, Sobi (NovImmune), Grant/research support from: AB2Bio, Novartis, Sobi (NovImmune), Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, Pfizer, Roche, Paid instructor for: Novartis, Pfizer (funds go to CCHMC/employer), Consultant of: Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, UCB (funds go to CCHMC/employer), Grant/research support from: Bristol Myers Squibb, Pfizer (funds go to CCHMC/employer).

Poststreptococcal reactive arthritis (PSRA) is associated with prior group A β-hemolytic streptococcal infection and has a reported annual incidence of 1 to 2 cases per 100,000 persons, approximately twice that of acute rheumatic fever (ARF) in the US. Children who present with reactive arthritis are not uncommon in a busy general pediatric practice in the US, whereas children who present with ARF are very rare. Distinguishing PSRA from ARF can be challenging because the symptoms and signs are similar, but the diseases differ in long-term therapy, follow-up evaluation, and prognosis. We review the diagnostic criteria for PSRA, the pertinent features of the 2015 ARF diagnostic guideline from the American Heart Association, and the major characteristics that differentiate PSRA from ARF.

Background The efficacy of SC abatacept (ABA) in patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA) was shown in a 2-year (yr), Phase III, open-label international study (NCT01844518).1 However, it is unknown whether each individual pt within a treatment group consistently achieves the same efficacy endpoint at all time points. Objectives To investigate whether ABA efficacy is maintained by individual pts with pJIA over time. Methods In this subgroup analysis, pts in two age cohorts (2–5 yrs and 6–17 yrs) who achieved clinical response to weekly SC ABA (10 to Results A total of 219 pts entered the study (46 [21.0%] 2–5 yrs; 173 [79.0%] 6–17 yrs) and a subgroup of these pts achieved a clinical response at Day 113 (Table). Most pts who achieved JIA-ACR70, JIA-ACR100, JADAS71 MDA and JADAS71 ID at Day 113 sustained their response at Day 393 and at Days 393 and 645 in the 2–5-yr and 6–17-yr cohorts (Figure). Across cohorts, more than 75% and 60% of pts maintained a JIA-ACR 70 and JADAS71 MDA response through Day 645, respectively. Prior biologic (b)DMARD use was an important prognostic factor. In pts aged 6–17 yrs, sustained JIA-ACR70 response rate at Days 393 and 645 was 81% (57/70) in pts who did not have prior bDMARDs vs 57% (12/21) in pts who had prior bDMARDs (p=0.0715); sustained JADAS71 MDA response rate was 71% (37/52) vs 37% (7/19; p=0.0320). Prognostic factors for JIA-ACR100 response and JADAS71 ID in pts aged 6–17 yrs and for all outcomes in pts aged 2–5 yrs could not be determined due to low pt numbers. Conclusion The majority of individuals with pJIA who achieved stringent efficacy endpoints with weekly SC abatacept by Day 113 sustained that clinical endpoint over time. Prior bDMARD use may be a prognostic factor for sustained response over 2 yrs. Reference [1] Brunner HI, et al. Arthritis Rheumatol2018;70:1144–54. Acknowledgement Professional medical writing: Stacey Reeber, PhD, Caudex; funding: Bristol-Myers Squibb Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus ( I perform consultancy activities on behalf of the Gaslini Institute for the companies listed below: AbbVie, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, R-Pharm. The money received for these activities are directly transferred to the Gaslini Institute’s bank account. Before March 2016, I was the head of the Pediatric Rheumatology Department at the G. Gaslini Hospital, where the PRINTO Coordinating Centre is located. For the coordination activity of the PRINTO network, the Gaslini Hospital received contributions from the industries listed in this section. This money has been reinvested for the research activities of the hospital in fully independent manners besides any commitment with third parties., Daniel J Lovell Consultant for: Consulting fees and/or honoraria from Astra Zeneca, Wyeth Pharma, Amgen, Abbott, Pfizer, F. Hoffmann-La Roche, Novartis, UBC, Takeda, GSK, Boehringer, and Celgene

Objectives To assess efficacy & safety of intravenous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy through 28 weeks of treatment. Methods A multicenter, Phase 3, single arm, open-label trial was conducted using intravenous golimumab at a dose of 80mg/m2 given at weeks 0 & 4, then every 8 weeks thereafter, in pediatric patients ages 2-17 years old with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy. Patients received commercial MTX weekly at same BSA-based dose as at time of study entry. All the results below are based on full analysis set which includes all patients who received at least 1 dose of study agent. Results 180 patients were screened (130 enrolled, 127 treated) with the first patient screened on 22Dec2014; last patient first treated 26Dec2017, & last patient’s Wk28 visit was 09Jul2018. Proportion of JIA ACR 30,50,70, & 90 responders at Wk28 was 83.5%,79.5%,70.1%, & 46.5%, respectively. 29.1% of patients met criteria for inactive disease at Wk28. Median change from baseline for JASDAS 10, 27, & 71 was -14.20, -16.60, & -20.32, respectively at Wk28. JADAS 10, 27, & 71 minimal disease activity was met by 15% of patients at Wk28. Proportion of patients experiencing at least 1 treatment-emergent AE through Wk28 was 77.2%. MedDRA system organ class with highest incidence of AEs was Infections & infestations (57.5%);most commonly reported AE upper respiratory tract infection(17.3%), then nasopharyngitis(15.0%).Six patients experienced serious AEs through Wk28: Herpes zoster disseminated, Infective exacerbation of bronchiectasis, Sepsis, Varicella, Mycosis fungoides, & Suicidal ideation. These events resulted in permanent discontinuation of intravenous golimumab, except for Varicella. Conclusion Intravenous golimumab delivered at a dose of 80mg/m2 at weeks 0 & 4, then every 8 weeks thereafter and appears to be effective in these patients with a safety profile similar to other TNF inhibitor therapies. Disclosure of Interests Nicolino Ruperto Grant/research support from: The Gaslini Hospital, where NR works as full-time public employee, has received contributions (> 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Consultant for: Received honoraria for consultancies or speaker bureaus (

ObjectiveTo investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).MethodsIn a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.ResultsLD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.ConclusionsA rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Objective To determine the efficacy in improving pain and health-related quality of life (HRQOL) of an online self-management program for adolescents with juvenile idiopathic arthritis (JIA). Methods Youth ages 12-18 years with JIA were recruited from 10 rheumatology clinics across the United States and randomized to complete an online self-management program (n = 144) or an online disease education program (n = 145). Participants in the self-management group worked through multimedia-based modules comprising psychoeducation, training in cognitive-behavioral coping skills and stress management, and other self-management topics over a 12-week period. Participants in the control group viewed a series of preselected quality educational websites about JIA over the same interval. Online content for both groups was made available in English and Spanish to facilitate inclusion of Hispanic participants. Blinded assessment of main outcomes (pain intensity, pain interference, and HRQOL) and process outcomes (disease knowledge, self-efficacy, pain coping, and emotional adjustment) occurred at baseline, posttreatment, and at 6- and 12-month postrandomization follow-up visits. Results Participants on average demonstrated significant improvements over the study period in the main outcomes, with no significant group differences in the degree of improvement. Effect sizes for these improvements were small. The amount of improvement in self-efficacy, emotional avoidance coping, disease knowledge, and emotional functioning in part predicted improvement in pain and HRQOL outcomes. Conclusions Primarily self-directed online self-management training and online disease education comparably and modestly improve pain and HRQOL in youth with JIA.

ObjectiveThis report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).MethodsIn this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0–16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16–48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.ResultsAmong 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with ConclusionAlthough the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.Clinical Trial RegistrationNCT01230827; Results.

Background In patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA), SC abatacept (ABA) 125 mg weekly has a similar pharmacokinetic profile, therapeutically equivalent efficacy and comparable safety to IV ABA 10 mg/kg every 4 weeks.1 Although some data on paediatric pt-reported outcomes (PRO) have been published for IV ABA,2 PRO data following treatment with SC ABA have not. Objectives This analysis examined the effect of SC ABA treatment on PROs (activities of daily living [ADL] limitation questionnaire of parent/caregiver, childhood HAQ [CHAQ]-DI, and parent global assessment of overall pt well-being [PaGA]) in 6–17-year pts with active pJIA in a Phase III trial (NCT01844518). Methods Pts with pJIA aged 2–17 years with an inadequate response/intolerance to ≥1 DMARD were enrolled in this single-arm, open-label study and received SC ABA weekly for 4 months based on body weight tier (10– 50 kg [125 mg ABA]). JIA-ACR 30 criteria (ACR Pediatric 30) responders at Month 4 could receive ABA for another 20 months. For the 6–17-year cohort reported here, ADL limitation questionnaire of parent/caregiver (mean [SD] number of days [D] of parental/caregiver missed activity, paid care and missed school [absolute values per month and percentage of D missed per month relative to an assumed average of 20 school D/month]); CHAQ-DI (0–3 scale across 8 domains of disability component); and PaGA (0–100 mm visual analogue scale) were evaluated. Results Baseline characteristics of the 173 pts with pJIA from the 6–17-year cohort were: median (min, max) age, 13.0 (6.0, 17.0) years; median (min, max) number of active joints, 10.0 (2.0, 42.0); 78.6% of pts used MTX (median dose: 11.6 mg/m2/week); and 26.6% were with prior biologic failure. All ADL limitation components improved from baseline to D113 (Month 4); these improvements were largely maintained at D309 (Figure). Relative percentage D missed from school decreased from 15% (D1) to 5.5% (D309, Figure D). CHAQ-DI and PaGA improved from baseline to D309 (Table). Further 2-year data are pending. Conclusions In this analysis of patients with pJIA aged 6–17 years, SC abatacept demonstrated a beneficial effect on PROs including reductions in activity limitation and disability (CHAQ-DI) and improvement in well-being (PaGA) up to D309. References Lovell D, et al. Arthritis Rheumatol 2016;68(suppl 10): Abstract 948. Ruperto N, et al. Arthritis Care Res 2010;62:1542–51. Disclosure of Interest N. Ruperto Grant/research support from: The G. Gaslini Hospital has received contributions from the following industries for the coordination activity of the PRINTO network: Bristol-Myers Squibb, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer,sanofi-aventis, Schwarz Biosciences, Abbott, Francesco Angelini S.P.A., Sobi, Merck Serono, Consultant for: AbbVie, Amgen, Biogen Idec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, sanofi-aventis, Servier, Takeda, UCB Biosciences GmbH, Speakers bureau: AbbVie, Amgen, Biogen Idec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, sanofi-aventis, Servier, Takeda, UCB Biosciences GmbH, H. Brunner: None declared, N. Tzaribachev: None declared, G. Vega-Cornejo: None declared, I. Louw: None declared, J. Anton Grant/research support from: Bristol-Myers Squibb, Novartis, Pfizer, AbbVie, GSK, Sobi, Roche, Alexion, Sanofi, Genzyme, Consultant for: Novartis, Sobi, Roche, Gebro, Pfizer, AbbVie, Alexion, Speakers bureau: Novartis, AbbVie, Pfizer, Sobi, Roche, Gebro, D. Viola: None declared, I. Foeldvari: None declared, V. Keltsev: None declared, D. Kingsbury: None declared, C. Wouters: None declared, B. Lauwerys: None declared, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, R. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Martini: None declared, D. Lovell Grant/research support from: National Institutes of Health, NIAMS, Consultant for: AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, Speakers bureau: Genentech

To determine the relationships among race, income, and disease outcomes in children with juvenile dermatomyositis (JDM).Data from 438 subjects with JDM enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry were analyzed. Demographic data included age, sex, race, annual family income, and insurance status. Clinical outcomes included muscle strength, presence of rash, calcinosis, weakness, physical function, and quality of life measures. Disease outcomes were compared based on race and income.Minority subjects were significantly more likely to have low annual family income and significantly worse scores on measures of physical function, disease activity, and quality of life measures. Subjects with lower annual family income had worse scores on measures of physical function, disease activity, and quality of life scores, as well as weakness. Black subjects were more likely to have calcinosis. Despite these differences in outcome measures, there were no significant differences among the racial groups in time to diagnosis or duration of disease. Using calcinosis as a marker of disease morbidity, black race, annual family income$50 000 per year, negative antinuclear antibody, and delay in diagnosis12 months were associated with calcinosis.Minority race and lower family income are associated with worse morbidity and outcomes in subjects with JDM. Calcinosis was more common in black subjects. Further studies are needed to examine these associations in more detail, to support efforts to address health disparities in subjects with JDM and improve disease outcomes.

Objective.Granulomatosis with polyangiitis (Wegener’s; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative.Methods.Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference).Results.MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA.Conclusion.EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.

Objective.There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician’s global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS v.3 in pediatric vasculitis is not known. We assessed the association of BVAS v.3 scores with PGA, treatment decision, and erythrocyte sedimentation rate (ESR) at diagnosis in pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods.Children with AAV diagnosed between 2004 and 2010 at all ARChiVe centers were eligible. BVAS v.3 scores were calculated with a standardized online tool (www.vasculitis.org). Spearman’s rank correlation coefficient (rs) was used to test the strength of association between BVAS v.3 and PGA, treatment decision, and ESR.Results.A total of 152 patients were included. The physician diagnosis of these patients was predominantly granulomatosis with polyangiitis (n = 99). The median BVAS v.3 score was 18.0 (range 0–40). The BVAS v.3 correlations were rs = 0.379 (95% CI 0.233 to 0.509) with PGA, rs = 0.521 (95% CI 0.393 to 0.629) with treatment decision, and rs = 0.403 (95% CI 0.253 to 0.533) with ESR.Conclusion.Applied to children with AAV, BVAS v.3 had a weak correlation with PGA and moderate correlation with both ESR and treatment decision. Prospective evaluation of BVAS v.3 and/or pediatric-specific modifications to BVAS v.3 may be required before it can be formalized as a disease activity assessment tool in pediatric AAV.

Objective To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Methods Eligible patients had been diagnosed by site rheumatologists (termed the “MD diagnosis”) since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. Results MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4–17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0–49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). Conclusion The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers.

Item does not contain fulltext Characteristic features of the 12q14 microdeletion syndrome include low birth weight, failure to thrive, short stature, learning disabilities and Buschke-Ollendorff lesions in bone and skin. This report on two additional patients with this microdeletion syndrome emphasizes the rather constant and uniform phenotype encountered in this disorder and refines the critical region to a 2.61 Mb interval on 12q14.3, encompassing 10 RefSeq genes. We have previously shown that LEMD3 haploinsufficiency is responsible for the Buschke-Ollendorff lesions and now provide strong evidence that a heterozygous deletion of HMGA2 is causing the growth failure observed in this disorder. The identification of an intragenic HMGA2 deletion in a boy with proportionate short stature and the cosegregation of this deletion with reduced adult height in the extended family of the boy further underscore the role of HMGA2 in regulating human linear growth.

The class I protein HLA-B27 confers susceptibility to inflammatory arthritis in humans and when overexpressed in rodents for reasons that remain unclear. We demonstrated previously that HLA-B27 heavy chains (HC) undergo endoplasmic reticulum (ER)-associated degradation. We report here that HLA-B27 HC also forms two types of aberrant disulfide-linked complexes (dimers) during the folding and assembly process that can be distinguished by conformation-sensitive antibodies W6/32 and HC10. HC10-reactive dimers form immediately after HC synthesis in the ER and constitute at least 25% of the HC pool, whereas W6/32-reactive dimers appear several hours later and represent less than 10% of the folded HC. HC10-reactive dimers accumulate in the absence of tapasin or beta(2)-microglobulin, whereas W6/32-reactive dimers are not detected. Efficient formation of W6/32-reactive dimers appears to depend on the transporter associated with antigen processing, tapasin, and beta(2)-microglobulin. The unpaired Cys(67) and residues at the base of the B pocket that dramatically impair HLA-B27 HC folding are critical for the formation of HC10-reactive ER dimers. Although certain other alleles also form dimers late in the assembly pathway, ER dimerization of HLA-B27 may be unique. These results demonstrate that residues comprising the HLA-B27 B pocket result in aberrant HC folding and disulfide bond formation, and thus confer unusual properties on this molecule that are unrelated to peptide selection per se, yet may be important in disease pathogenesis.

Adalimumab (ADA) is approved for use in moderate to severe juvenile idiopathic arthritis (JIA) in patients (pts) ≥4 years (yrs) old in the US, EU, and Japan. Limited data are available in pts

OBJECTIVE Mice deficient in beta2-microglobulin (beta2m), but expressing the human major histocompatibility complex (MHC) class I molecule HLA-B27, have been reported to develop spontaneous inflammatory arthritis (SA). We sought to determine whether, under certain conditions, beta2m deficiency alone was sufficient to cause SA, and if this might be a result of class I deficiency. METHODS The following types of mice were produced: mice of the MHC b haplotype genetically deficient in beta2m (beta2m(0)) on several genetic backgrounds (C57BL/6J [B6], BALB/cJ, SJL/J, MRL/MpJ, and B6,129), mice deficient in the transporter associated with antigen processing (TAP1(0)) on a B6,129 background, and HLA-B27-transgenic beta2m(0) mice on a B6 background. Cohorts were transferred from specific pathogen-free (SPF) to conventional (non-SPF) animal rooms, and evaluated clinically and histologically for the development of SA. RESULTS SA occurred in TAP1(0) and beta2m(0)/class I-deficient mice with a mixed B6,129 genome at a frequency of 30-50%, while 10-15% of B6, SJL/J, and BALB/cJ beta2m(0) mice developed this arthropathy. MRL/ MpJ beta2m(0) mice were unaffected. Expression of B27 did not increase the frequency of SA in B27-transgenic B2m(0) B6 mice compared with that in beta2m(0) B6 controls. CONCLUSION Class I deficiency is sufficient to cause SA in mice. The frequency of disease, as well as B27-specific SA, is markedly dependent on a non-MHC genetic background. These results suggest that class I deficiency in a genetically susceptible mouse can mimic B27-associated arthropathy.

The assembly of eukaryotic 20 S proteasomes involves the formation of half-proteasomes where precursor beta-type subunits gather in position on an alpha-subunit ring, followed by the association of two half-proteasomes and beta-subunit processing. In vertebrates three additional beta-subunits (beta1i/LMP2, beta2i/MECL1, and beta5i/LMP7) can be synthesized and substituted for constitutive homologues (beta1/delta, beta2/Z, and beta5/X) to yield immunoproteasomes, which are important for generating certain antigenic peptides. We have shown previously that when all six beta-subunits are present, cooperative assembly mechanisms limit the diversity of proteasome populations. Specifically, LMP7 is incorporated preferentially over X into preproteasomes containing LMP2 and MECL1. We show here that the LMP7 propeptide is responsible for this preferential incorporation, and it also enables LMP7 to incorporate into proteasomes containing delta and Z. In contrast, the X propeptide restricts incorporation to proteasomes with delta and Z. Furthermore, we demonstrate that the LMP7 propeptide can function in trans when expressed on LMP2, and that its NH(2)-terminal and mid-regions are particularly critical for function. In addition to identifying a novel propeptide function, our results raise the possibility that one consequence of LMP7 incorporation into both immunoproteasomes and delta/Z proteasomes may be to increase the diversity of antigenic peptides that can be generated.

The objective of this study was to assess the safety of adalimumab in patients aged 2 to

Background JIA is the most common chronic inflammatory rheumatic diseases of childhood. Due to their long-term safety and efficacy, biologic disease modifying antirheumatic drugs (DMARD) are commonly necessary for control of pJIA patients (pts). Objectives To evaluate 6-year (y) safety and 2 y effectiveness profile of Adalimumab with or without methotrexate (ADA±MTX) when used in current clinical practice for the treatment of moderately to severely active pJIA. Methods This is a 6 y interim analysis of an ongoing, multicenter, non-interventional, observational registry of pts with moderately to severely active pJIA with up to10 y safety follow-up. Included pts are treated with either ADA±MTX or MTX alone as part of their routine clinical care enrolled in the US, EU, and Australia. MedDRA observational adverse events (AEs) were recorded from the first day in the registry through last contact, irrespective of the duration of registry treatment. Effectiveness was assessed by 27-joint juvenile arthritis disease activity score (JADAS27), based on CRP. Results As of January 2014, enrollment was complete. As of June 1, 2015 cut-off date, 846 pts (543 in ADA±MTX and 303 in MTX groups) were treated in the registry. There were 39 pts who rolled over from the MTX to the ADA±MTX arm. At registry entry mean pJIA disease duration was 1.4 y and 3.7 y for MTX and ADA±MTX arms, respectively. At baseline (BL), mean AJC71 was 5.8 and 5.3 for MTX and ADA±MTX arms, respectively, and Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) was 0.6 for both arms. At data cutoff, the mean duration of study exposure was 1.81 y and 2.15 y for MTX and ADA±MTX arms, respectively. Overall, 206 pts (68%) in the MTX and 216 pts (39.8%) in the ADA±MTX arms discontinued registry drug through 6 y. The main reasons for registry drug discontinuation for the MTX arm: pts required additional therapy (32.3%), other (11.9%), lack of efficacy (10.9%), AEs (8.3%), or pts achieved JIA remission (7.6%), and for ADA±MTX arm: lack of efficacy (16%), lost to follow-up (7.2%), other (5.9%), and AEs (5.3%). Frequencies and rates of treatment-emergent AEs were similar to those reported for observational AEs (Table). There were no reports of deaths, malignancies, opportunistic infections, active TB, oral candidiasis, or CHF. Mean JADAS27 (CRP) improved from 12.2 at BL to 9.7, 5.2, 4.4, 3.5, 2.2 at months 1, 6, and 12, 18, 24 for pts in the MTX and from 11.8 at BL to 7.0, 4.-2, 4.2, 3.6, 3.9 in the ADA±MTX arms, respectively (observed data). Conclusions Overall, ADA±MTX was well-tolerated in these pts with pJIA with no new safety signals. Discontinuations from the registry drug were relatively high through 6 y, but greater in the MTX only arm. Acknowledgement AbbVie sponsored the study & contributed with PRINTO & PRCSG to the analysis, review, and approval of the abstract. Xiaolei Leahy & Ashish Deshmukh of AbbVie contributed to the research. Medical writing support was provided by Gaurav Patki, PhD, of AbbVie. Disclosure of Interest N. Ruperto Grant/research support from: AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfgroupaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Phgroupaceuticals., Employee of: GASLINI Hospital, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche, and Wyeth/Pfizer, D. J. Lovell Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, and Genentech, Speakers bureau: Wyeth Pharmaceuticals, and served on data and safety monitoring boards for Amgen and Forest Research, C. Wallace Grant/research support from: Pfizer and Amgen, Consultant for: Amgen and Novartis., M. Toth: None declared, I. Foeldvari Consultant for: AbbVie and Novartis, J. Bohnsack Consultant for: Novartis, D. Milojevic Consultant for: Genentech and Novartis, E. Rabinovich Grant/research support from: UCB Pharma, Janssen Research & Development, LLC, Hoffmann-La Roche Inc., and AbbVie, D. Kingsbury Grant/research support from: AbbVie, K. Marzan Grant/research support from: AbbVie., P. Quartier Grant/research support from: AbbVie, Novartis, Consultant for: AbbVie, Novartis, K. Minden Grant/research support from: Pfizer and Abbvie, Consultant for: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac and Pharma-Allergan., E. Chalom Speakers bureau: AbbVie, G. Horneff Grant/research support from: AbbVie, Pfizer, and Roche, Speakers bureau: AbbVie, Novartis, Pfizer, and Roche, R. M. Kuester Grant/research support from: AbbVie Inc. and Wyeth/Pfizer, J. Dare Grant/research support from: AbbVie, AstraZeneca, Bristol-Myers Squibb, Horizon Pharma, Medac, Pfizer, Roche, and UCB, M. Heinrich Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, H. Kupper Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, J. Kalabic Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, A. Martini Grant/research support from: AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Pharmaceuticals, Employee of: GASLINI Hospital, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, and MedImmune., H. I. Brunner Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Boehringer-Ingelheim, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UCB, and Genentech, Speakers bureau: Genentech Pharmaceuticals.

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives Report the pharmacokinetics (PK), safety and taste acceptability of tofacitinib following multiple oral doses in patients (pts) 2

Background IV abatacept (ABA) 10 mg/kg every 4 weeks is safe and effective in reducing signs and symptoms of polyarticular forms of juvenile idiopathic arthritis (pJIA) in children and adolescents. 1 SC ABA 125 mg weekly has therapeutically equivalent efficacy and comparable safety to IV ABA in adult RA, but similar data in pJIA are lacking. Objectives To assess the PK, efficacy and safety of SC ABA in children and adolescents with active pJIA. Methods This single-arm, open-label (OL), Phase III study (NCT01844518) enrolled patients (pts) aged 2–17 years (yrs) with pJIA and an inadequate response/intolerance to ≥1 DMARD. Pts received SC ABA weekly OL for 4 months (M), based on body weight tier (10– 50 kg [125 mg ABA]). JIAACR criteria 30 (JIAACR30) responders at 4M could enter a 20M OL extension; JIAACR30 non-responders could continue SC ABA for 3M more and discontinued if JIAACR30 was not achieved by M7. The primary endpoint was steady-state blood trough concentration (C minss ) of ABA at 4M in the 6–17-yr-old pJIA pts (n=173); we report PK, efficacy and safety from the initial 4M OL phase for these pts. Results Baseline characteristics of the 173 pJIA pts were: mean age (SD) =12.3 (3.1) yrs; mean number of active joints (SD) =12.4 (8.3); 78.6% of patients used MTX (mean dose: 12 mg/m 2 /week) and 26.6% failed prior biologic treatment. The target therapeutic C minss of 10 μg/mL was achieved (Figure); at 4M, mean (SD) C minss was 42.1 (14.7) μg/mL and was consistent across all three weight groups. Robust JIAACR responses were seen at 4M (Figure): JIAACR30, 80.9%; inactive disease, 29.5%. Biologic-naive pts had a numerically higher JIAACR30 response than biologic-experienced pts at 4M. The number of pts with serious AEs and those who discontinued study drug due to AEs during the initial 4M were low (n=5 and n=3 [fatigue, exanthematous rash and ovarian germ cell teratoma] pts, respectively). AEs of interest reported included infections (31.8%) with 1 case of sepsis, injection-site reactions (5.2%) and malignancy (0.6%). No laboratory abnormalities or unexpected safety concerns were reported. Conclusions The target therapeutic exposure for SC abatacept was achieved in pts aged 6–17 yrs with pJIA irrespective of weight group. The exposures for SC abatacept were within the range for IV abatacept in pJIA and comparable with SC abatacept in adult RA. Robust efficacy was observed with SC abatacept with no new safety concerns after 4M of treatment. References Ruperto N, et al. Lancet 2008;372:383–91. Disclosure of Interest N. Ruperto Grant/research support from: Gaslini Hospital, Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, sanofi aventis, Schwarz Biosciences, Sobi, Consultant for: AbbVie, Amgen, Biogen Idec, Baxalta, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman-La Roche, Janssen, Novartis, Pfizer, Servier, Sinergie,Takeda, Speakers bureau: AbbVie, Amgen, Biogen Idec, Baxalta, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman-La Roche, Janssen, Novartis, Pfizer, Servier, Sinergie,Takeda, D. J. Lovell Grant/research support from: NIH, Consultant for: AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, N. Tzaribachev Grant/research support from: UCB, Pfizer, Janssen, Roche, G. Vega-Cornejo: None declared, I. Louw: None declared, A. Berman: None declared, I. Calvo Grant/research support from: Novartis, Speakers bureau: AbbVie, Roche, Novartis, Sobi, R. Cuttica: None declared, G. Horneff Grant/research support from: Pfizer, AbbVie, Roche, F. Avila-Zapata: None declared, J. Anton Grant/research support from: Pfizer, Novartis, Speakers bureau: Pfizer, AbbVie, Novartis, Sobi, Roche, D. Viola: None declared, I. Foeldvari: None declared, V. Keltsev: None declared, D. Kingsbury: None declared, X. Li Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, R. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Martini Grant/research support from: The Gaslini Hospital, which is the public Hospital where I work as full time public employee, has received contributions from the following industries: Abbott, Bristol-Myers Squibb, “Francesco Angelini”, GlaxoSmithKline, Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, sanofi aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Consultant for: Abbott, AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Astellas, Boehringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, H. I. Brunner Consultant for: Pfizer, Bristol-Myers Squibb, UCB, Janssen, Amgen, Celgene, AstraZeneca, Novartis, Genentech, Speakers bureau: Novartis, Genentech

Objective.To determine whether adult disease severity subclassification systems for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are concordant with the decision to treat pediatric patients with cyclophosphamide (CYC).Methods.We applied the European Vasculitis Study (EUVAS) and Wegener’s Granulomatosis Etanercept Trial (WGET) disease severity subclassification systems to pediatric patients with AAV in A Registry for Childhood Vasculitis (ARChiVe). Modifications were made to the EUVAS and WGET systems to enable their application to this cohort of children. Treatment was categorized into 2 groups, “cyclophosphamide” and “no cyclophosphamide.” Pearson’s chi-square and Kendall’s rank correlation coefficient statistical analyses were used to determine the relationship between disease severity subgroup and treatment at the time of diagnosis.Results.In total, 125 children with AAV were studied. Severity subgroup was associated with treatment group in both the EUVAS (chi-square 45.14, p < 0.001, Kendall’s tau-b 0.601, p < 0.001) and WGET (chi-square 59.33, p < 0.001, Kendall’s tau-b 0.689, p < 0.001) systems; however, 7 children classified by both systems as having less severe disease received CYC, and 6 children classified as having severe disease by both systems did not receive CYC.Conclusion.In this pediatric AAV cohort, the EUVAS and WGET adult severity subclassification systems had strong correlation with physician choice of treatment. However, a proportion of patients received treatment that was not concordant with their assigned severity subclass.

Background/Purpose: Adalimumab (ADA) is approved for use in moderate to severe juvenile idiopathic arthritis (JIA) in patients (pts) ≥4 years (yrs) old in the US, EU, and Japan, and was recently approved in EU for pts aged 2 to

Background/Purpose: To assess efficacy and safety of SC golimumab (GLM) in polyarticular pediatric juvenile idiopathic arthritis pts (aged 2 to

Background The long-term safety of anti-tumor necrosis factor (TNF) drugs is particularly important in pediatric patients (pts) who may require prolonged treatment of their inflammatory disease. Objectives To evaluate long-term rates of serious adverse events (AE) and anti-TNF AEs of special interest in adalimumab (ADA) clinical trials in pediatric pts with polyarticular or polyarticular course juvenile idiopathic arthritis (pJIA) or enthesitis-related arthritis (ERA). Methods Safety data from pts treated with ADA, either dosed 24 mg/m 2 BSA every other week (eow) or 20 mg eow ( Results ADA was administered to 274 pts, representing 769.0 PY of exposure. Infections, the most common AE, occurred in ≥10% of pts. Serious infection was the most frequently reported SAE (table). One case of latent TB was reported. No malignancies, opportunistic infections, or deaths were reported. 8.4% of pts (23/274) discontinued study due to AE (range, 5.1% in age Conclusions These data provide support for the long-term safety of ADA in pediatric pts aged 2–17 yrs with pJIA or ERA and demonstrate a safety profile consistent with ADA in adult pts and known information about the anti-TNF class. Acknowledgements AbbVie funded the studies (NCT00048542, NCT00690573, NCT00775437, and NCT01166282), contributed to their design and was involved in the collection, analysis, and interpretation of the data, and in the writing, review, and approval of the publication. Medical writing support was provided by Kathleen V. Kastenholz, PharmD, MS, of AbbVie. Disclosure of Interest N. Ruperto Grant/research support from: AbbVie, AstraZeneca, BMS, Janssen, “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, and Wyeth for the PRINTO network paid to GASLINI Hospital, Consultant for: AbbVie, Amgen, Astellas, Alter, AstraZeneca, Biogen Idec, Boehringer, BMS, CD-Pharma, Celgene, Crescendo Bioscience, EMD Serono, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo-Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Sinergie, Takeda, and Vertex, Speakers bureau: AbbVie, Amgen, Astellas, Alter, AstraZeneca, Biogen Idec, Boehringer, BMS, CD-Pharma, Celgene, Crescendo Bioscience, EMD Serono, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo-Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Sinergie, Takeda, and Vertex, D. Lovell Consultant for: AbbVie, AstraZeneca, Boehringer Ingelheim, Celgene, Centocor, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Horizon Pharma, Janssen Biologics B.V., Novartis, Pfizer, Regeneron, Hoffman La-Roche, and UBC and served on data and safety monitoring boards for Forest Research, Speakers bureau: Genentech and Wyeth Pharmaceuticals, D. Kingsbury Grant/research support from: AbbVie, R. Burgos-Vargas Grant/research support from: AbbVie, Consultant for: AbbVie, BMS, Janssen, Pfizer, and Roche, Speakers bureau: AbbVie, BMS, Janssen, Pfizer, and Roche, T. Imagawa Grant/research support from: AbbVie/Eisai and Novartis, Consultant for: AbbVie/Eisai, Speakers bureau: AbbVie/Eisai, Chugai, and Mitsubishi Pharma, G. Horneff Grant/research support from: AbbVie, Pfizer, and Roche, Speakers bureau: AbbVie, Novartis, Pfizer, and Roche, P. Quartier Grant/research support from: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum, Consultant for: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum, S. Goodman Consultant for: Amgen, A. Reiff Consultant for: AbbVie and Amgen, Speakers bureau: AbbVie and Amgen, E. Giannini Consultant for: AbbVie, A. Cardoso Shareholder of: AbbVie, Employee of: AbbVie, J. Anderson Shareholder of: AbbVie, Employee of: AbbVie, N. Varothai Shareholder of: AbbVie, Employee of: AbbVie, J. Kalabic Shareholder of: AbbVie, Employee of: AbbVie, A. Martini Grant/research support from: AbbVie, AstraZeneca, BMS, Janssen, “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, and Wyeth for the PRINTO network paid to GASLINI Hospital, Consultant for: AbbVie, Amgen, Biogen Idec, Boehringer, BMS, Celgene, EMD Serono, Janssen, MedImmune, Medac, Novartis, Novo- Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Takeda, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, Boehringer, BMS, Celgene, EMD Serono, Janssen, MedImmune, Medac, Novartis, Novo- Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Takeda, and Vertex

Background The Juvenile Arthritis Disease Activity Score (JADAS) is increasingly accepted for defining a treat-to-target strategy in patients (pts) with juvenile idiopathic arthritis (JIA)1 Objectives To use JADAS to evaluate clinical disease activity/control, with or without functional control, in pts with polyarticular or polyarticular-course JIA (pJIA), following the initiation of adalimumab (ADA) ± concurrent methotrexate (MTX) treatment. To assess the feasibility of JADAS definition of remission (REM) and minimal disease activity (MDA) as part of a treat-to-target strategy. Methods Data for this post hoc analysis originated from M10-444, an open-label study in pJIA pts 2 to Results Out of 32 pts, 25 (78%) had received prior MTX and 27/32 (84%) received concomitant MTX during the study. At baseline, pts had a mean JADAS10 of 18.8, JADAS27 of 19.0, and DI-CHAQ of 1.2. After 12 wks on open-label ADA, improvements were observed in clinical and functional outcomes. At wks 12 and 24, the mean JADAS10 was 6.2 and 5.3; mean JADAS27 was 6.4 and 5.6; mean DI-CHAQ was 0.7 and 0.7, respectively. No pts were in REM/MDA at baseline; however after 12 and 24 wks, a sizeable proportion achieved disease control (table). After 12 and 24 wks of ADA treatment, the proportions of pts achieving both, disease control and DI-CHAQ Conclusions Addition of open-label ADA treatment resulted in clinically important improvements in clinical and functional outcomes in pts with pJIA. JADAS 10 and -27 gave comparable results. JADAS REM and MDA are achievable targets with ADA treatment. References Consolaro et al, Arth & Rheum. 2012. Acknowledgements AbbVie sponsored the study, participated in the design, data collection, analysis, and interpretation; and in the writing of the final version. Medical writing support was provided by Naina Barretto, PhD, of AbbVie Disclosure of Interest D. Kingsbury Grant/research support from: AbbVie, P. Quartier Grant/research support from: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum, Consultant for: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum, G. Horneff Grant/research support from: AbbVie, Pfizer, Roche, Speakers bureau: AbbVie, Novartis, Pfizer, and Roche, K. Minden Grant/research support from: Pfizer and Abbvie, Consultant for: Pfizer, Abbvie, Roche and Pharm-Allergan, M. Toth: None declared, N. Varothai Employee of: AbbVie, A. Cardoso Employee of: AbbVie, J. Kalabic Employee of: AbbVie

Background Juvenile idiopathic arthritis (JIA) is one of the most common childhood rheumatic diseases. Adalimumab (ADA) is approved for moderate to severe polyarticular JIA (pJIA) in patients (pts) ≥4 yrs in Australia and Japan and for pts ≥2 yrs in the US and EU. Objectives To evaluate long-term safety and effectiveness of ADA in pts with moderately to severely active pJIA who are prescribed and treated with ADA in routine clinical practice. Methods This is an ongoing, multicenter, non-interventional, observational registry of pts with moderately to severely active pJIA who are treated with either ADA ± methotrexate (MTX) or MTX alone as part of their routine clinical care. 800 pts (500 ADA/300 MTX) were to be enrolled in the US, EU, and Australia. The follow-up observational period is 10 yrs from enrollment into one of the treatment arms. Observational adverse events (AEs) were recorded from the first day in the registry through last contact, irrespective of registry treatment duration. Clinical outcomes were assessed by 27-joint juvenile arthritis disease activity score (JADAS27), based on CRP. 5 yr interim data are presented. Results As of January 2014, enrollment is complete. 842 pts (540 ADA/302 MTX) were treated as of the March 28, 2014 cutoff. Mean pJIA disease duration at enrollment was 1.3 and 3.7 yrs and mean duration of study exposure was 643 and 653 days for MTX and ADA arms, respectively. Baseline mean AJC73 was 5.8 and 5.4 for MTX and ADA, respectively, and CHAQ-DI was 0.6 for both groups. Overall, 153 pts (50.7%) in the MTX arm and 132 pts (24.4%) in the ADA arm discontinued registry drug. Of those, 22 (7.3%) and 23 (4.3%) in the MTX and ADA arm, respectively, discontinued due to an AE, and 39 of the 153 pts in the MTX arm discontinued as they switched to the ADA arm. The observational AEs are summarized (Table). No deaths, malignancies, or opportunistic infections were reported. In the ADA arm, there were 13 (2.4%) pts with serious infectious AEs (abdominal abscess, acute tonsillitis, appendicitis, cellulitis, gastroenteritis, mononucleosis, viral meningitis, pneumonia, pyelonephritis, scarlet fever, subcutaneous abscess, tonsillitis, urinary tract infection, and varicella). Frequencies and rates of treatment-emergent AEs were similar to those reported for observational AEs. Mean JADAS27 improved from 12.1 at baseline to 9.4, 6.1, 5.1, 4.4 at months 1, 3, 6, and 12 for pts in the MTX arm and from 12.1 at baseline to 7.4, 5.5, 4.4, 4.5 in the ADA arm, respectively (observed data). Conclusions Overall, ADA is well-tolerated in these pts with active pJIA. No new safety signals were observed, and based on this interim analysis, the known safety profile of ADA remains unchanged. Acknowledgements AbbVie sponsored the study (NCT00783510), contributed with PRINTO and PRCSG to the design, and participated in data collection, analysis, and interpretation, and in the writing, review, and approval of the abstract. Medical writing support was provided by Jessica L. Suboticki, PhD, of AbbVie. Disclosure of Interest N. Ruperto Employee of: GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, and Wyeth Pharmaceuticals. NR has served on speaker9s bureau for Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, Janssen Biologics B.V., MedImmune, Roche, and Wyeth/Pfizer, H. Brunner Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Boehringer-Ingelheim, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UCB, and Genentech, Speakers bureau: Genentech Pharmaceuticals, C. Wallace Grant/research support from: Pfizer, Amgen, Consultant for: Amgen, Novartis, M. Toth: None declared, I. Foeldvari Consultant for: AbbVie, Novartis, J. Bohnsack Consultant for: Novartis, D. Milojevic Consultant for: Genentech, Novartis, E. Rabinovich Grant/research support from: UCB Pharma, Janssen Research & Development, LLC, Hoffmann-La Roche Inc., AbbVie, P. Vavrincova: None declared, D. Kingsbury Grant/research support from: AbbVie, K. Marzan Grant/research support from: AbbVie, P. Quartier Grant/research support from: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, Swedish Orphan Biovitrum; Participates on a data management committee of a phase 3 trial by Sanofi, Consultant for: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, Swedish Orphan Biovitrum, K. Minden Grant/research support from: Pfizer, Abbvie, Consultant for: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac, Pharm-Allergan, Speakers bureau: Pfizer, Abbvie, Roche/Chugai, Novartis, Medac, Pharm-Allergan, E. Chalom Speakers bureau: AbbVie, G. Horneff Grant/research support from: AbbVie, Pfizer, and Roche and speaker9s fees from AbbVie, Novartis, Pfizer, Roche, R.-M. Kuester Grant/research support from: AbbVie, Wyeth/Pfizer, J. Dare Grant/research support from: AbbVie, AstraZeneca, Bristol-Myers Squibb, Horizon Pharma, Medac GmbH, UCB Biosciences, M. Bereswill Shareholder of: AbbVie, Employee of: AbbVie, H. Kupper Shareholder of: AbbVie, Employee of: AbbVie, J. Kalabic Shareholder of: AbbVie, Employee of: AbbVie, A. Martini Employee of: GASLINI Hospital, which has received contributions to support the research activities of the network of PRINTO from AbbVie Inc., AstraZeneca, Bristol-Myers Squibb, Janssen Biologics B.V., Eli Lilly and Co., “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals, Speakers bureau: Astellas, AstraZeneca, Bristol-Myers Squibb, Italfarmaco, MedImmune, D. Lovell Consultant for: AbbVie Inc., AstraZeneca, Centocor, Bristol-Myers Squibb, Pfizer, Regeneron, Hoffman La-Roche, Novartis, UBC, Xoma, Genentech; served on data and safety monitoring boards for Amgen, Forest Research, Speakers bureau: Wyeth Pharmaceuticals

Background Interleukin (IL)-1β plays a key role in the pathogenesis of systemic juvenile idiopathic arthritis (SJIA). Canakinumab (CAN), a selective, fully human, anti-IL-1β monoclonal antibody, has been shown to be efficacious in the treatment of SJIA. 1 Objectives To analyze gene expression and inflammatory proteins in blood of SJIA patients (pts) on CAN therapy.To identify biomarkers that predict clinical response to CAN treatment at baseline. Methods Inflammatory protein biomarkers (IL-6; IL-18) and gene expression profiles of active SJIA pts (aged 2 to Results Gene expression : Changes upon CAN treatment at Day 3 were assessed. Using identical filtering criteria (≥2 fold, p≤0.05), no CAN responsive genes were found for placebo (n=9) or for CAN (n=11) treated pts that were non-responders (adapted pediatric [ACR]30 not achieved) at Day 15. In contrast, 171 probesets passed this filter for responder pts (n=52, ≥ACR30), all of whom received CAN. Strongly repressed genes included many inflammation- and innate immunity-related genes (eg, IL-1β, IL1R1, IL1R2, TLR1, TLR4, TLR5). A set of transcripts was identified for which high baseline expression levels predicted a majority of strong (≥ACR50) responders. However, baseline transcript levels of a second, smaller subgroup of strong CAN responders, were similar to ACR30 responders and non-responders which in turn resembled levels found in healthy controls (n=22). Upon CAN treatment, transcript levels largely returned to those resembling healthy controls in the majority of strong responders. Protein markers : IL-6 protein levels were reduced by Day 3 (-4.7x and -4.4x with p=0.002 and 0.0001, n=20 and n=51 for the respective 2 trials), and at Day 29 (-12.5x and -8.1x with p=0.01 and 0.00005, n=20 and n=65). Greater reduction at Days 3 and 29 was observed for pts with strong Day 15 ACR response. IL-18 levels were mostly unchanged until Day 29 and with only moderate reduction at Day 57. Conclusions Canakinumab treatment resulted in a rapid, strong reduction of many pro-inflammatory transcripts and serum IL-6, while IL-18 levels showed a delayed, weaker reduction. A majority of strong treatment responders were characterized by a set of transcripts with high baseline levels which reduced to healthy subject levels with treatment while other strong responders did not show elevation of these transcripts at baseline, suggesting heterogeneity at the molecular level in SJIA pts benefitting from canakinumab. References Ruperto N. et al. N Engl J Med 2012;367:2396-406. Disclosure of Interest A. Brachat Shareholder of: Novartis, Employee of: Novartis, A. Grom Consultant for: Novartis, Roche, NovImmune, N. Wulffraat Grant/research support: AbbVie, Roche, Consultant for: Novartis, Pfizer, Roche, H. Brunner Consultant for: Novarits, Roche, Astrazeneca, Celgene, Pfizer, Janssen, UCB, GSK, BMS, Speakers bureau: Novartis, P. Quartier Grant/research support: AbbVie, Chigai-Roche, Novartis, Pfizer, Consultant for: Chugai-Roche, Novartis, Pfizer, Speakers bureau: Abbott/AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, Servier, SOBI, R. Brik Grant/research support: Novartis, Consultant for: Novartis, L. McCann: None declared, H. Ozdogan Consultant for: Novartis, L. Rutkowska-Sak: None declared, R. Schneider Consultant for: Novartis, Roche, V. Gerloni: None declared, L. Harel: None declared, M. Terreri: None declared, K. Houghton: None declared, R. Joos: None declared, D. Kingsbury: None declared, J. Lopez-Benitez: None declared, S. Bek Employee of: Novartis, M. Schumacher Employee of: Novartis, M. Valentin Shareholder of: Novartis, Employee of: Novartis, H. Gram Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/research support: BMS, Centocor,GSK, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences: To Gaslini Hospital to support PRINTO research, Consultant for: BMS, Centocor,GSK, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences:To Gaslini Hospital to support PRINTO research, Speakers bureau: Abbott, BMS, Astellas, Boehringer, Italfarmaco, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi Aventis, Roche, Servier, N. Ruperto Grant/research support: Abbott, Astrazeneca, BMS, Centocor, Eli Lilly, Francesco Angelini, GSK, Italfarmaco, Novartis, Pfizer/Wyeth, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma: to Gaslini Hospital, Speakers bureau: Astrazeneca, BMS, Janssen Biologics BV, Roche, Pfizer/Wyeth, D. Lovell Grant/research support: National Institutes of Health-NIAMS, Consultant for: Astra-Zeneca, Centocor, Amgen, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Speakers bureau: Novartis, Roche, N. Nirmala Employee of: Novartis DOI 10.1136/annrheumdis-2014-eular.2320

Background Adalimumab (ADA) is approved for use in moderate to severe JIA in patients (pts) ≥4 yrs old in the US, EU, and Japan. ADA has not been studied in pts Objectives To assess safety and effectiveness of ADA in pts 2 to Methods This is a multicenter, open-label, Phase 3b study in pts 2 to 2 BSA up to 20 mg/dose, for a minimum of 24 wks or until pts reached 4 yrs old and weighed 15 kg. Concomitant use of DMARDs was allowed. Key effectiveness endpoints were the proportion of pts achieving PedACR30/50/70/90 at wk 24. Other outcomes were tender joint count (TJC), swollen joint count (SJC), Pain on Passive Motion (POM75), Limitation on Passive Motion (LOM69), Active Joint Count (AJC73), Child Health Assessment Questionnaire (DICHAQ), Physician’s Global Assessment of Disease (PhGA), and Parent’s Global Assessment (PaGA) of Disease and Pain. Adverse events (AE) are being collected throughout the treatment period and include safety data up to 96 wks. Results 88% of the pts were female. At baseline, mean age was 3 yrs, mean weight=13 kg, mean JIA duration=12 months, and 39% had elevated CRP (≥0.9 mg/dL). Of 32 pts enrolled, 31 completed 24 wks of treatment. At wk 24, 90% of pts had achieved PedACR30 (Table 1). Improvements in other JIA outcomes were also seen at wk 24 of ADA treatment (Table 2). AE incidence rates included: any AEs (84%, 27/32), serious AEs (16%, 5/32), infectious AEs (69%, 22/32), and serious infections (9%, 3/32); no deaths, malignancies, opportunistic infections/TB, congestive heart failure, demyelinating disease, allergic reactions, lupus-like syndrome, or blood dyscrasias were reported. Conclusions Adalimumab was safe and effective in younger JIA patients (2 to Disclosure of Interest D. Kingsbury Grant/Research support from: Abbott, P. Quartier Grant/Research support from: Abbott, Novartis, Pfizer, Consultant for: Abbott, S. Santra Shareholder of: Abbott, Employee of: Abbott, H. Kupper Shareholder of: Abbott, Employee of: Abbott, N. Mozaffarian Shareholder of: Abbott, Employee of: Abbott

Organ system-involvement in SLE and relationship with demographic factors, disease duration and health-related quality of life in childhood SLE Lakshmi N Moorthy, Maria J Baratelli, Margaret GE Peterson, Afton L Hassett, Alexa B Adams, Laura V Barinstein, Emma J MacDermott, Elizabeth C Chalom, Karen Onel, Linda I Ray, Jorge Lopez-Benitez, Christina Pelajo, Kathleen A Haines, Daniel J Kingsbury, Victoria W Cartwright, Philip J Hashkes, Nora G Singer, Gina A Montealegres, Ingrid Tomanova-Soltys, Andreas O Reiff, Sandy D Hong, Thomas JA Lehman

IL-1β, an inflammatory cytokine, plays an important role in SJIA, a rare autoinflammatory disease. Canakinumab (CAN), a selective fully human, anti-IL-1β monoclonal antibody, is reported to be efficacious in treating SJIA.