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Klotsche J.,A Leibniz Institute | Klotsche J.,Charite - Medical University of Berlin | Niewerth M.,A Leibniz Institute | Haas J.-P.,German Center for Pediatric and Adolescent Rheumatology | And 6 more authors.
Annals of the Rheumatic Diseases | Year: 2015

Importance Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. Objectives To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. Design, setting and participants Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. Main outcomes and measures We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). Results Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). Conclusions and relevance Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort. © 2015 BMJ Publishing Group Ltd & European League Against Rheumatism. Source

Dueckers G.,HELIOS Childrens Hospital | Guellac N.,University of Federal Defense Munich | Arbogast M.,Rheumazentrum Oberammergau | Dannecker G.,Olgahospital | And 13 more authors.
Clinical Immunology | Year: 2012

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and adolescents. Immunomodulatory drugs are used frequently in its treatment. Using the nominal group technique (NGT) and Delphi method, we created a multidisciplinary, evidence- and consensus-based treatment guideline for JIA based on a systematic literature analysis and three consensus conferences. Conferences were headed by a professional moderator and were attended by representatives who had been nominated by their scientific societies or organizations. 15 statements regarding drug therapy, symptomatic and surgical management were generated. It is recommended that initially JIA is treated with NSAID followed by local glucocorticoids and/or methotrexate if unresponsive. Complementing literature evidence with long-standing experience of caregivers allows creating guidelines that may potentially improve the quality of care for children and adolescents with JIA. © 2011 Elsevier Inc. Source

Merker J.,TU Munich | Hartmann M.,German Center for Pediatric and Adolescent Rheumatology | Kreuzpointner F.,TU Munich | Schwirtz A.,TU Munich | Haas J.-P.,German Center for Pediatric and Adolescent Rheumatology
Pediatric Rheumatology | Year: 2015

Background: Patients suffering from juvenile idiopathic arthritis (JIA) frequently have affected ankle joints, which can lead to foot deformities such as pes planovalgus (JIA-PPV). Usually, JIA-PPV is diagnosed by examining the foot in non-weightbearing or in weightbearing, static condition. However, functional limitations typically appear during dynamic use in daily activities such as walking. The aim of this study was to quantify the pathophysiology of JIA-PPV in both static and dynamic condition, i.e. in upright standing and during the stance phase of walking using three-dimensional (3d) gait analysis. Methods: Eleven JIA patients (age = 12y) with at least one affected ankle joint and fixed pes planovalgus (≥5°) were compared to healthy controls (CG) (n = 14, age = 11y). Kinematic and kinetic data were obtained in barefoot standing and walking condition (1.1-1.3 m/s) with an 8-camera 3d motion analysis system including two force-plates and one pressure distribution plate. All participants were prepared using reflecting markers according to the Oxford Foot and Plug-in-Gait Model. Results were compared using the Mann-Whitney-U-test and Wilcoxon signed-rank test (p < 0.05). Results: In comparison to CG, JIA-PPV had an excessive hindfoot/tibia eversion (p < 0.001) and a forefoot/hindfoot supination (p < 0.001) in both static and walking condition. JIA-PPV showed a greater hindfoot/tibia eversion during walking (midstance) compared to standing (p = 0.021) in contrast to CG. The arch index, measured by plantar pressure distribution, indicates a reduced arch height in JIA-PPV (p = 0.007). Patients had a lower maximum dorsiflexion of hindfoot/tibia (p = 0.001) and a lower plantarflexion of forefoot/hindfoot (p = 0.028), both when standing and walking. The kinetic results showed lower maximum ankle dorsiflexion moments (p < 0.037) as well as generated ankle power (p = 0.086) in JIA-PPV. Conclusions: The pathophysiology of JIA-PPV during walking indicated that excessive hindfoot eversion produces accessory symptoms such as a reduced arch height, increased forefoot supination and reduced propulsion effect of the ankle. Muscular and coordinative insufficiency caused by arthritis can lead to the observed increased hindfoot eversion from static to dynamic condition. Conventional static or passive foot examination techniques probably underestimate deformity in JIA pes planovalgus. 3d gait analysis might be helpful in early diagnosis of this condition, especially in JIA patients with affected ankle joints. © 2015 Merker et al. Source

Karg M.,University of Waterloo | Seiberl W.,TU Munich | Kreuzpointner F.,TU Munich | Kreuzpointner F.,German Center for Pediatric and Adolescent Rheumatology | And 2 more authors.
IEEE Transactions on Neural Systems and Rehabilitation Engineering | Year: 2015

In clinical gait analysis, the gait of a patient is recorded with optical motion capture and compared with a healthy reference group. High-dimensional gait datasets are difficult to interpret; machine learning can provide guidance regarding the most relevant gait phases and joint angles for visual analysis and quantify the difference between healthy and pathological gait. We propose an explicit state duration hidden Markov model (HMM) modeling the timeseries data of a subject or a group and the use of a reference-based measure that compares the most likely observations in each state. Based on this stochastic framework, the similarity between healthy and pathological gait can be quantified for each state, each joint angle, and each subject. This concept also includes an overall gait index useful for group comparison or the assessment of an individual's gait. For visualization, joint angle timeseries can be generated from the explicit state duration HMM. The accuracy of the explicit state duration HMM and the performance of the reference-based measures are evaluated on a dataset including strides of healthy subjects and patients suffering from arthritis. © 2001-2011 IEEE. Source

Hu gle B.,German Center for Pediatric and Adolescent Rheumatology | Hinze C.,German Center for Pediatric and Adolescent Rheumatology | Hinze C.,University Childrens Hospital Mu nster | Lainka E.,University of Duisburg - Essen | And 2 more authors.
Pediatric Rheumatology | Year: 2014

Background: Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory disease. However, sJIA patients may develop aggressive arthritis without systemic inflammation later in the disease, resembling an autoimmune phenotype similar to other subtypes of JIA. The objective of this study was to determine whether antinuclear antibodies (ANA) and rheumatoid factor (RF) will develop in patients with sJIA over the course of the disease.Findings: A single center sample of sJIA patients with follow-up of more than one year was obtained. A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers ≥ 1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers ≥ 1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p = 0.001). In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart. Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p = 0.425) or positive RF (p = 0.703).Conclusions: Patients with sJIA developed increased ANA titers and positive RF over the course of the disease, independent of treatment with TNF antagonists. This might point towards an autoimmune, rather than an autoinflammatory phenotype later in the course of sJIA. © 2014 Hu¨gle et al.; licensee BioMed Central Ltd. Source

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