OP0291 TOFACITINIB FOR THE TREATMENT OF POLYARTICULAR COURSE JUVENILE IDIOPATHIC ARTHRITIS: RESULTS OF A PHASE 3, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED WITHDRAWAL STUDY

Background:Tofacitinib is an oral JAK inhibitor that is being investigated for JIA.Objectives:To assess tofacitinib efficacy and safety in JIA patients (pts).Methods:This was a Phase 3, randomised, double-blind (DB), placebo (PBO)-controlled withdrawal study in pts aged 2−<18 years with polyarticular course JIA (pcJIA), PsA or ERA (NCT02592434). In the 18-week open-label Part 1, pts received weight-based tofacitinib doses (5 mg BID or lower). Pts with ≥JIA ACR30 response at Week (W)18 were randomised 1:1 in the DB Part 2 (W18−44) to continue tofacitinib or switch to PBO. Primary endpoint: disease flare rate by W44. Key secondary endpoints: JIA ACR50/30/70 response rates; change from Part 2 baseline (Δ) in CHAQ-DI at W44. Other efficacy endpoints: time to disease flare in Part 2; JADAS27-CRP in Parts 1 and 2. PsA/ERA pts were excluded from these efficacy analyses. Safety was evaluated in all pts up to W44.Results:225 enrolled pts with pcJIA (n=184), PsA (n=20) or ERA (n=21) received tofacitinib in Part 1. At W18, 173/225 (76.9%) pts entered Part 2 (pcJIA n=142, PsA n=15, ERA n=16). In pcJIA pts, disease flare rate in Part 2 was significantly lower with tofacitinib vs PBO by W44 (p=0.0031; Fig 1a). JIA ACR50/30/70 response rates (Fig 1b) and ΔCHAQ-DI (Fig 1c) at W44, and time to disease flare in Part 2 (Fig 2a), were improved with tofacitinib vs PBO. Tofacitinib reduced JADAS27-CRP in Part 1; this effect was sustained in Part 2 (Fig 2b). Overall, safety was similar with tofacitinib or PBO (Table): 77.3% and 74.1% had adverse events (AEs); 1.1% and 2.4% had serious AEs. In Part 1, 2 pts had herpes zoster (non-serious) and 3 pts had serious infections (SIs). In Part 2, SIs occurred in 1 tofacitinib pt and 1 PBO pt. No pts died.Conclusion:In pcJIA pts, tofacitinib vs PBO resulted in significantly fewer disease flares, and improved time to flare, disease activity and physical functioning. Tofacitinib safety was consistent with that in RA pts.Table.Safety in all ptsPart 1Part 2TofacitinibaN=225TofacitinibaN=88PBO N=85Pts with events, n (%)AEs153 (68.0)68 (77.3)63 (74.1)SAEs7 (3.1)1 (1.1)2 (2.4)Permanent discontinuations due to AEs26 (11.6)16 (18.2)29 (34.1)AEs of special interest Death000 Gastrointestinal perforationb000 Hepatic eventb3 (1.3)00 Herpes zoster (non-serious and serious)2 (0.9)c00 Interstitial lung diseaseb000 Major adverse cardiovascular eventsb000 Malignancy (including non-melanoma skin cancer)b000 Macrophage activation syndromeb000 Opportunistic infectionb000 SI3 (1.3)1 (1.1)d1 (1.2) Thrombotic event (deep vein thrombosis, pulmonary embolismbor arterial thromboembolism)000 Tuberculosisb000a5 mg BID or equivalent weight-based lower dose in pts <40 kgbAdjudicated eventscBoth non-seriousdOne SAE of pilonidal cyst repair was coded to surgical procedures instead of infections, and was inadvertently not identified as an SI. Following adjudication, the SAE did not meet opportunistic infection criteria; it is also included in the table as an SIAE, adverse event; BID, twice daily; PBO, placebo; pts, patients; SAE, serious AE; SI, serious infectionAcknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Olga Synoverska Speakers bureau: Sanofi, Tracy Ting: None declared, Carlos Abud-Mendoza Speakers bureau: Eli Lilly, Pfizer Inc, Alberto Spindler Speakers bureau: Eli Lilly, Yulia Vyzhga Grant/research support from: Pfizer Inc, Katherine Marzan Grant/research support from: Novartis, Vladimir Keltsev: None declared, Irit Tirosh: None declared, Lisa Imundo: None declared, Rita Jerath: None declared, Daniel Kingsbury: None declared, Betül Sözeri: None declared, Sheetal Vora: None declared, Sampath Prahalad Grant/research support from: Novartis, Elena Zholobova Grant/research support from: Novartis and Pfizer Inc, Speakers bureau: AbbVie, Novartis, Pfizer Inc and Roche, Yonatan Butbul Aviel: None declared, Vyacheslav Chasnyk: None declared, Melissa Lerman Grant/research support from: Amgen, Kabita Nanda Grant/research support from: Abbott, AbbVie, Amgen and Roche, Heinrike Schmeling Grant/research support from: Janssen, Pfizer Inc, Roche and USB Bioscience, Heather Tory: None declared, Yosef Uziel Speakers bureau: Pfizer Inc, Diego O Viola Grant/research support from: Bristol-Myers Squibb, GSK, Janssen and Pfizer Inc, Speakers bureau: AbbVie and Bristol-Myers Squibb, Holly Posner Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Keith Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ann Wouters Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cheng Chang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Richard Zhang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Irina Lazariciu Consultant of: Pfizer Inc, Employee of: IQVIA, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ricardo Suehiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alberto Martini Consultant of: AbbVie, Eli Lily, EMD Serono, Janssen, Novartis, Pfizer, UCB, Daniel J Lovell Consultant of: Abbott (consulting and PI), AbbVie (PI), Amgen (consultant and DSMC Chairperson), AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (PI), Celgene, Forest Research (DSMB Chairman), GlaxoSmithKline, Hoffman-La Roche, Janssen (co-PI), Novartis (consultant and PI), Pfizer (consultant and PI), Roche (PI), Takeda, UBC (consultant and PI), Wyeth, Employee of: Cincinnati Children's Hospital Medical Center, Speakers bureau: Wyeth, Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novarti

Manipulating the Hype: contemporary art's response to media cliches

Manipulating the Hype addresses art’s reaction to the barrage of signs produced by the media. The paper researches contemporary art’s response to clichéd media stereotypes and elucidates artists’ multifaceted perspective on overtly obvious yet widely embraced paradigms marketed by the media. Contemporary art’s strategic reconfiguration of media stereotypes is a valuable introspection upon the superficiality and impracticability of advertising and entertainment industry constructs. By reconsidering the mediated image, art has the ability to inspire reevaluation of cultural values. The thesis additionally attempts to ascertain the reinterpretation of media stereotypes as a common thread linking principal art movements and historically significant artworks from around the world since 1960. How does contemporary art respond to the extensive cultural influence of the media? Is a reaction to mass media a thematic commonality linking contemporary artists in the age of globalization? Manipulating the Hype is a dual outcome investigation comprised of written thesis and studio practice. The written thesis combines experience from a lengthy professional practice with historical and theoretical research. The visual thesis consists of twelve photographic works taken at on the Big Island of Hawaii. The images juxtapose artificial icons of power from popular culture with the natural force of the active lava flow. The process of research discloses how the advertising and entertainment industries capitalize upon innate human desires through the manipulative proliferation of archetypal imagery. Furthermore, the thesis establishes the widespread retort to media clichés as a palpable commonality in studio practices worldwide. The findings in the research make evident that although contemporary art does not have sufficient influence to reform the media, it can heighten public awareness of media tactics

Systemic lupus erythematosus [Sistemik lupus eritematozus]

Systemic lupus erythematosus in children and adolescents is a multisystem autoimmune disease with a great variability in disease presentation and course. Approximately 15% of the patients with systemic lupus erythematosus (SLE) have the onset of their disease in childhood or adolescence. The common symptoms of SLE in children and adolescents include fever, fatigue, weight loss, arthritis, rash and renal disease. Although it is a life-long and serious disease with a high morbidity and mortality rate, the prognosis has dramatically improved with the aggressive use of high dose corticosteroids combined with other potent anti-inflammatory agents. This article summarizes available epidemiologic data, pathogenesis, clinical patterns, approaches to investigation and treatment, and recent outcome data

Effect of colchicine-resistant familial mediterranean fever on growth parameters [Kolşisine dirençli ailesel akdeniz ateşinin büyüme parametlerine etkisi]

Objectives: This study aims to evaluate the growth and development in patients with Familial Mediterranean fever (FMF) resistant to colchicine treatment. Patients and methods: Eighty-seven patients (45 females, 42 males; mean age 9.6±3.8 years; range 2 to 17 years) diagnosed with FMF according to Tel Hashomer criteria in the Pediatric Nephrology Department of Ege University Faculty of Medicine were included in the study. All patients had leukocytosis and elevated C-reactive protein, fibrinojen levels, erythrocyte sedimentation rate and serum amyloid A levels during attacks. The patients were divided into t wo group s accor ding to colchicines treatment response. Twenty-seven patients (13 girls, 14 boys; mean age; 9.9±3.2 years) having frequent attacks (>1 attact/3 month) despite receiving 2 mg/day colchicine treatment were defined as colchicine-resistant. Sixty patients were defined as colchicine treatment responders. Anthropometric evaluations of the patients were performed at diagnosis and at the end of the follow-up. The height and weight Z scores of patients were used as growth parameters. Results: No statistically significant difference in mutation frequency was found between the groups. There were no significant differences between both groups in the weight and height Z scores calculated from the anthropometric parameters detected at the diagnosis. In the evaluation performed at the end of the follow-up, we found that the height and weight score for age and the body mass index Z score were significantly decreased in the colchicine resistance group (p=0.008, p=0.013, p=0.027). Conclusion: Effective suppression of inflammatory response in patients with FMF provides a positive impact on growth. While colchicine is known as the most effective drug in the treatment of FMF, it is known that there are also patients who fail to respond adequately. The patients with colchicine-resistant FMF should be identified in the early period of the disease and treatment should be arranged accordingly. The detection of growth retardation was found to be important in detecting resistance to colchicine in patients with FMF. © 2011 Turkish League Against Rheumatism. All rights reserved

Is the childhood primary hypertension causes target organ damage? [Çocukluk yaş grubunda primer hipertansiyon hedef organ tutulumu yapar mi?]

Objective: The primary hypertension in childhood that is related with high cardiovascular morbidity and mortality has been a serious health problem in recent years and has become more important. In this study, the exploration of the effects of traditional and nontraditional risk factors over target organ damage in children with primary hypertension is aimed. Material and Methods: 50 patients who are between 7-18 years old and diagnosed as primary hypertension and 100 healthy children in the same age as a control group were evauated in study. Ambulatory blood pressure measurement within 24 hours was performed to the patient group. Biochemically, blood lipids, hs CRP, Lp(a) were measured. In terms of target organ involvement, retinopathy, nephropathy (microalbuminuria in 24-hour urine), cardiopathy (left ventricular hypertrophy and left ventricular mass index) and vasculopathy (carotid intima-media thickness and arterial stiffness) were evaluated. Results: In all 50 patients (35 boys, 15 girls), average age 13,1±3,2 years old and in all members of healthy control group (54 boys, 46 girls) average age is 13,06±2,7 years old. In 17 of patients (34%) there was hypertensive retinopathy (14 of them is (%28) in phase 1, 3 of them (%6) is in phase 2). In 1 patient (2%) echocardiographic left ventricular hypertrophy was seen. In 7 patients (14%) left ventricular mass index was high (Avg: 28.32±11.43 gr/m2,7). In 26 patients (52%), cIMT (on right 0.468±0.062, on left 0.472±0.064 mm and in control group, on right 0.406±0.041, in left 0.405±0.041; p=0,000), in 18 patients (36%), PWV (5.76±0.84 m/s, in control group 5,30±0,70 m/s; p=0.000), in 11 patient (22%), central augmentation index (10.54±6.56%, in control group 9.41±8.54%; p=0.366) was high. As the severity of the disease increases, the indicators of microalbuminuria and inflammation also increased significantly but it showed a decrease in HDL levels. Varying degrees of target organ involvement was found in 8 patients with white coat hypertension. Conclusion: The primary hypertension in childhood that causes target organ damage must be early recognized and treated. © Copyright 2016 by Türkiye Klinikleri