Effect of probiotics on clinical and immune parameters in enthesitis‐related arthritis category of juvenile idiopathic arthritis A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis‐Related Arthritis Psoriatic arthritis (PA): a clinical, immunological and radiological study of 180 patients. Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry Naproxen in juvenile chronic polyarthritis. Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register A short-term follow-up of enthesitis and arthritis in the active phase of juvenile onset spondyloarthropathies. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis. Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register Preliminary validation of clinical remission criteria using the OMERACT filter for select categories of juvenile idiopathic arthritis. Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis. Hepatitis B vaccination in children with juvenile idiopathic arthritis Sulphasalazine. An alternative drug for second-line treatment of juvenile chronic arthritis. Abatacept improves health‐related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis Two-year Efficacy and Safety of Etanercept in Pediatric Patients with Extended Oligoarthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis Anti-adalimumab antibodies in a cohort of patients with juvenile idiopathic arthritis: incidence and clinical correlations Pharmacokinetics and Pharmacodynamics of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis. Clinical manifestations and responsiveness to adalimumab are similar in patients with ankylosing spondylitis with and without concomitant psoriasis. Efficacy of measles, mumps and rubella revaccination in children with juvenile idiopathic arthritis treated with methotrexate and etanercept. Safety of measles, mumps and rubella vaccination in juvenile idiopathic arthritis Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis. Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis. Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis. A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features. High prevalence of temporomandibular joint arthritis at disease onset in children with juvenile idiopathic arthritis, as detected by magnetic resonance imaging but not by ultrasound. Longterm Safety and Effectiveness of the Anti-interleukin 6 Receptor Monoclonal Antibody Tocilizumab in Patients with Systemic Juvenile Idiopathic Arthritis in Japan Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. Clinical responsiveness of self-report functional assessment measures for children with juvenile idiopathic arthritis undergoing intraarticular corticosteroid injections. Benefit of fluoroscopically guided intraarticular, long-acting corticosteroid injection for subtalar arthritis in juvenile idiopathic arthritis A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis. Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial. Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis. The relationship between health-related quality of life, pain, and coping strategies in juvenile arthritis – A one year prospective study Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. Patterns of pain over time among children with juvenile idiopathic arthritis Effective seroconversion and safety following the pandemic influenza vaccination (anti-H1N1) in patients with juvenile idiopathic arthritis A prospective study comparing infection risk and disease activity in children with juvenile idiopathic arthritis treated with and without tumor necrosis factor-alpha inhibitors The Relationship Between Physical Activity Levels and Pain in Children with Juvenile Idiopathic Arthritis Pilot study of fitness training and exercise testing in polyarticular childhood arthritis. Is high-resolution ultrasonography suitable for the detection of temporomandibular joint involvement in children with juvenile idiopathic arthritis? Long‐Term Safety, Efficacy, and Quality of Life in Patients With Juvenile Idiopathic Arthritis Treated With Intravenous Abatacept for Up to Seven Years Markedly decreased antibody titers against hepatitis B in previously immunised children presenting with juvenile idiopathic arthritis. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Health-Related Quality of Life, Physical Function, Fatigue, and Disease Activity in Children with Established Polyarticular Juvenile Idiopathic Arthritis
Gut microflora and dysbiosis as an environmental factor has been linked to the pathogenesis of enthesitis‐related arthritis ( JIA‐ERA ) ; thus , we performed a proof‐of‐concept study of probiotics to modulate the gut‐flora and study the effects on immune and clinical parameters of children having JIA‐ERA . Forty‐six children with active JIA‐ERA were r and omized to placebo or probiotic therapy along with non‐steroidal anti‐inflammatory drugs ( NSAIDs ) for 12 weeks . Patients were assessed using a six‐point composite disease activity index ( mJSpADA ) based on morning stiffness , joint count , enthesitis count , sacroiliitis/inflammatory back pain , uveitis and erythrocyte sedimentation rate/C‐reactive protein ( ESR/CRP ) . Frequencies of T helper type 1 ( Th1 ) , Th2 , Th17 and regulatory T cells in blood were measured using flow cytometry . Serum cytokines interferon (IFN)‐γ , interleukin (IL)−4 , IL‐17 , IL‐10 , tumour necrosis factor (TNF)‐α and IL‐6 were measured by cytokine bead array using flow cytometer . The average age of 46 children ( 44 boys ) was 15 ± 2.5 years and duration of disease was 3.5 ± 3 years . There was no significant difference in improvement in mJSpADA between the two groups ( P = 0·16 ) . Serum IL‐6 levels showed a decrease ( P < 0·05 ) in the probiotic‐group . Th2 cell frequency ( P < 0·05 ) and serum IL‐10 levels ( P < 0·01 ) showed an increase in the placebo group , but again the probiotic use did not show a significant change in immune parameters when compared to the placebo . Adverse effects among the probiotic and placebo groups were diarrhea ( 36 versus 45 % ) , abdominal pain ( 9 versus 20 % ) , minor infections ( 4·5 versus 20 % ) and flatulence ( 23 versus 15 % ) , respectively . Thus , we can conclude that  probiotic therapy in JIA‐ERA children is well tolerated , but failed to show any significant immune or clinical effects over NSAID therapy Enthesitis‐related arthritis ( ERA ) is a juvenile idiopathic arthritis ( JIA ) category , primarily affecting entheses and peripheral joints . This study evaluated efficacy , safety , and pharmacokinetics of adalimumab versus placebo in patients with ERA We carried out a prospect i ve study of the clinical , laboratory and radiological features of 180 patients with psoriatic arthritis . We initially classified our patients into five groups as described in the publications of Moll and Wright . Thirty-seven per cent had oligoarthritis , 36 % polyarthritis , 23 % spondarthritis ( sacroiliitis and /or spondylitis ) and 4 % had the mutilans form . The distal joint arthritis type did not exist as an entity and the distal interphalangeal ( DIP ) joints were affected in all groups . The spondarthritis form includes patients with exclusively axial manifestations and also those who in addition have peripheral arthritis ( oligoarthritis , polyarthritis , DIP arthritis ) . Only 53 % of our patients had nail involvement . We found an increase of IgA levels in patients with axial disease . This suggests a relationship between ankylosing spondylitis and psoriatic spondylitis . The HLA-B17/Cw6 association increased in the oligoarticular form . The increase of antigen B17 correlated with the spondarthritic and oligoarthritis forms whereas Cw6 was more important in the oligoarthritis form . An increase of the HLA-B27/Cw1 association and the spondarthritic form was also found . Moreover , we detected a greater incidence of the HLA-B27 antigen in patients with bilateral sacroiliitis ( 85 % ) than in patients with unilateral sacroiliitis ( 22 % ) . Our work revealed that PA is not a harmless disease ; 57 % of our patients had erosive arthritis while 19 % had ARA class III or IV functional impairment Background This study aim ed to assess long-term safety and developmental data on juvenile idiopathic arthritis ( JIA ) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs ( nsNSAIDs ) .  Methods Children aged ≥2 to < 18 years with rheumatoid-factor – positive or –negative polyarthritis , persistent or extended oligoarthritis , or systemic arthritis were enrolled into this prospect i ve , observational , multicenter st and ard-of-care registry . Eligible patients were newly or recently prescribed ( ≤6 months ) an nsNSAID or celecoxib .  Enrolled patients were followed to the end of the study , whether they remained on the original NSAID , switched , or discontinued therapy altogether . All adverse events ( AEs ) regardless of severity were captured in the data base . Results A total of 274 patients ( nsNSAID , n = 219 ; celecoxib , n = 55 ) were observed for 410 patient-years of observation . Naproxen , meloxicam , and nabumetone were the most frequently used nsNSAIDs . At baseline , the celecoxib group was older , had a numerically longer median time since diagnosis , and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance . AEs reported were those frequently observed with NSAID treatment and were similar across groups ( nsNSAIDs : 52.0 % ; celecoxib : 52.9 % ) . Twelve unique patients experienced a total of 18 serious AEs ; the most frequent were infections , and none was attributed to NSAID use . Conclusions The safety profile of celecoxib and nsNSAIDs appears similar overall . The results from this registry , ongoing pharmacovigilance , and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive . Trial registration Clinical Trials.gov identifier NCT00688545 Naproxen at 10 mg per kg body weight was compared with aspirin at 80 mg per kg body weight in children suffering from juvenile chronic polyarthritis . It was found to be as effective as aspirin , with certainly no more and possibly fewer gastrointestinal side effects . A long-term tolerance study up to 12 months confirmed that naproxed was a satisfactory nonsteroidal anti-inflammatory drug in the management of various types of juvenile chronic arthritis Background Treatment of  juvenile idiopathic arthritis ( JIA ) has changed dramatically since the introduction of biological agents in 1999 . Objective To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA . Methods The Arthritis and Biologics in Children register ( multicentre prospect i ve observational study ) aim ed to include all consecutive patients with JIA in the Netherl and s who had started biological agents since 1999 . Patients were divided according to year of introduction of first biological agent . Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years . Results 335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010 . Etanercept remained the most often prescribed biological agent for non-systemic JIA ; anakinra became first choice for systemic JIA . The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased . During these 12 years of observation , biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS ( Juvenile Arthritis Disease Activity Score ) disease activity . All baseline disease activity parameters were lowered in patients with non-systemic JIA . In systemic JIA , prescription patterns changed towards very early introduction of biological agents ( median 0.4 years of disease duration ) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates . These changes for both systemic and non-systemic JIA result ed in more patients with inactive disease after 3 and 15 months of treatment . Conclusions Biological agents are increasingly prescribed , earlier in the disease and in patients with JIA with lower disease activity . These changes are accompanied by better short-term disease outcomes OBJECTIVE To describe the characteristics of enthesitis and arthritis in the active inflammatory stage of juvenile onset spondyloarthropathies ( SpA ) during a short-term follow-up . PATIENTS AND METHODS The study group included data of 33 patients with juvenile-onset SpA with enthesitis in > or = 3 sites , arthritis in > or = 4 joints , and erythrocyte sedimentation rate ( ESR ) of > or = 25 mm/h despite treatment , who participated in a 26-week , double-blind , sulfasalazine versus placebo trial that showed no significant differences between groups in regard to enthesitis and arthritis . RESULTS Twenty-seven boys and 6 girls ( mean age : 15.3 + /- 3.5 years ; mean disease duration : 4.1 + /- 2.7 years ) with the seronegative enthesopathy and arthropathy ( SEA ) syndrome ( n = 20 ) or ankylosing spondylitis ( AS ; n = 13 ) comprised the group . Throughout the study , the mean ( + /- SD ) number of swollen joints and tender entheses were 4.6 + /- 2.5 and 8.3 + /- 5.4 . The entheses and joints most frequently involved were the calcaneal attachments of the plantar fascia ( 87.9 % ) and Achilles tendon ( 81.8 % ) and the ankle ( 87.9 % ) and knee ( 72.7 % ) , respectively . There was pain in the cervical , thoracic , and lumbar spine in 39.4 % , 69.7 % , and 63.6 % of patients and in the sacroiliac joints in 48.5 % . Mid-foot involvement ( or tarsitis ) occurred in 29 patients ( 87.9 % ) . Except for the feet , the simultaneous occurrence of enthesitis and arthritis in other sites was rare . Overall , there were no significant differences between SEA syndrome and AS patients . CONCLUSIONS Disease activity shows a significant trend for entheses and joints of the feet and a significant prevalence of axial enthesitis in juvenile onset SpA. Mid-foot involvement appears to be the most characteristic and potentially , the most severe form of disease in these patients OBJECTIVE This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate ( MTX ) in children with selected categories of juvenile idiopathic arthritis ( JIA ) . METHODS Patients ages 2 - 18 years with rheumatoid factor (RF)-positive or RF-negative polyarthritis , systemic JIA , or extended oligoarthritis were eligible for the study . Patients received MTX alone ( > or = 10 mg/m(2)/week [ approximately 0.3 mg/kg/week ] , maximum dosage 1 mg/kg/week ) , etanercept alone ( 0.8 mg/kg/week , maximum dose 50 mg ) , or etanercept plus MTX for 3 years in an open-label , nonr and omized study . Safety was assessed by measuring rates of adverse events , and effectiveness was assessed using the physician 's global assessment of disease activity and the pediatric total joint assessment . RESULTS A total of 197 , 103 , and 294 patients were enrolled in the MTX , etanercept , and etanercept plus MTX groups , respectively . Exposure-adjusted rates of adverse events were similar among the 3 treatment groups ( 18.3 , 18.7 , and 21.6 per 100 patient-years in the MTX , etanercept , and etanercept plus MTX groups , respectively ) . Respective rates per 100 patient-years of serious adverse events ( 4.6 , 7.1 , and 6.0 ) and medically important infections ( 1.3 , 1.8 , and 2.1 ) were also similar among the 3 treatment groups . Scores for physician 's global assessment and total active joints improved from baseline , and improvement was maintained for the duration of the study . CONCLUSION These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA . Improvement was maintained for 3 years in those continuing to receive medication Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist . However , the spectrum of spondylarthropathy is wider than the sum of these disorders suggests . Seronegative oligoarthritis , dactylitis or polyarthritis of the lower extremities , heel pain due to enthesitis , and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria . In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy , we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases . The diagnoses were based on the local clinical expert 's opinion . The 403 patients included 168 with ankylosing spondylitis , 68 with psoriatic arthritis , 41 with reactive arthritis , 17 with inflammatory bowel disease and arthritis , and 109 with unclassified spondylarthropathy . Based on statistical analysis and clinical reasoning , we propose the following classification criteria for spondylarthropathy : inflammatory spinal pain or synovitis ( asymmetric or predominantly in the lower limbs ) , together with at least 1 of the following : positive family history , psoriasis , inflammatory bowel disease , urethritis , or acute diarrhea , alternating buttock pain , enthesopathy , or sacroiliitis as determined from radiography of the pelvic region . These criteria result ed in a sensitivity of 87 % and a specificity of 87 % . The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers . However , we regard them as preliminary until they have been further evaluated in other setting The histopathological characteristic of ankylosing spondylitis ( AS ) is the presence of chronic enthesitis . Our aim was to develop a clinical measurement of the severity of tenderness over entheses . The scoring system was based on the patients ' response to palpation over entheses easily accessible to examination . The enthesis index ( EI ) correlated with pain ( r = 0.67 , p less than 0.01 ) and stiffness ( r = 0.46 , p less than 0.05 ) scores . A single , blind , crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability . The index showed significantly lower scores after one week 's drug treatment ( p less than 0.05 ) . The EI is a convenient , non-invasive measure of disease severity in patients with AS . Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinical ly between severity of enthesitis and synovitis in different types of polyarthritis Objective : We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis ( JIA ) subtypes . Methods : At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept .  Disease activity was evaluated ( at start of the study , after 3 months and then yearly ) according to the JIA core set of the American College of Rheumatology paediatric definition for 30 , 50 and 70 % improvement ( ACR Pedi 30 , 50 and 70 ) . Use of etanercept and concomitant drugs was monitored . Adverse events were recorded . Results : We included 146 patients with JIA with a median follow-up of 2.5 years per patient ( range 0.3–7.3 ) . JIA subtypes represented : 27 % systemic , 8 % polyarticular rheumatoid factor positive , 38 % polyarticular rheumatoid factor negative , 19 % oligoarticular extended , 3 % enthesitis-related and 5 % psoriatica . Most patients ( 77 % ) met the criteria of the ACR Pedi 30 in the first 3 months of treatment . For the majority of patients this improvement was sustained ; 53 ( 36 % ) of all patients met the remission criteria . No other second-line agents were needed in 43 patients . Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes , those who did respond showed equal effectiveness in the long term . Serious adverse events rate was low ( 0.029 per patient year ) . Conclusions : Etanercept  is effective and safe in JIA , even for a large proportion of the patients with systemic JIA . The greatest improvement occurred in the first 3 months of treatment , and was sustained for a long time in most patients ( up to 75 months ) OBJECTIVE To begin the validation process of the preliminary criteria for inactive disease ( ID ) , clinical remission on medication ( CRM ) , and clinical remission off medication ( CR ) in children with select forms of juvenile idiopathic arthritis ( JIA ) . METHODS We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter 's 3 components : truth , discrimination , and feasibility , in 5 categories of JIA : systemic arthritis , persistent and extended oligoarthritis , and rheumatoid factor-positive and negative polyarthritis . Data sources for determining validity estimates included a Delphi question naire survey sent to 246 pediatric rheumatologists in 34 countries , a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries , a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years , and the literature . RESULTS Truth component : face and content validity . These aspects of validity were largely established via the Delphi question naire exercise and the consensus conference . Using an 80 % consensus level , participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID , CRM , and CR . Criterion validity could not be irrefutably established because no gold st and ard for inactive disease exists for JIA . As an alternative , published investigations of remission in JIA were used to estimate concurrent and convergent validity , as surrogates for criterion validity and as indicators of overall construct validity . Correlational analyses revealed the new criteria to have good construct validity . Discrimination component : the criteria demonstrated moderate to high levels of classification , prognosis , and responsiveness ( sensitivity to change ) using data from the chart review . Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM . Responsiveness was evidence d by the ability of the criteria to allow movement of most patients between the disease states , consistent with what is known of the course of the disease . Feasibility component : Results of the Delphi and consensus conference produced a set of criteria that are easily , quickly , and inexpensively completed in the physician 's office , and present minimal or no risk to the patient . CONCLUSION The preliminary criteria demonstrated moderate to excellent validity characteristics in some , but not all components of the OMERACT filter . Prospect i ve validation studies are under way Objective To investigate the efficacy and safety of etanercept ( ETN ) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods CLIPPER is an ongoing , Phase 3b , open-label , multicentre study ; the 12-week ( Part 1 ) data are reported here . Subjects with eoJIA ( 2–17 years ) , ERA ( 12–17 years ) , or PsA ( 12–17 years ) received ETN 0.8 mg/kg once weekly ( maximum 50 mg ) . Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology ( ACR ) 30 criteria at week 12 ; secondary outcomes included JIA ACR 50/70/90 and inactive disease . Results 122/127 ( 96.1 % ) subjects completed the study ( mean age 11.7 years ) . JIA ACR 30 ( 95 % CI ) was achieved by 88.6 % ( 81.6 % to 93.6 % ) of subjects overall ; 89.7 % ( 78.8 % to 96.1 % ) with eoJIA , 83.3 % ( 67.2 % to 93.6 % ) with ERA and 93.1 % ( 77.2 % to 99.2 % ) with PsA. For eoJIA , ERA , or PsA categories , the ORs of ETN vs the historical placebo data were 26.2 , 15.1 and 40.7 , respectively . Overall JIA ACR 50 , 70 , 90 and inactive disease were achieved by 81.1 , 61.5 , 29.8 and 12.1 % , respectively . Treatment-emergent adverse events ( AEs ) , infections , and serious AEs , were reported in 45 ( 35.4 % ) , 58 ( 45.7 % ) , and 4 ( 3.1 % ) , subjects , respectively . Serious AEs were one case each of abdominal pain , bronchopneumonia , gastroenteritis and pyelocystitis . One subject reported herpes zoster and another varicella . No differences in safety were observed across the JIA categories . Conclusions ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA , ERA and PsA , with no unexpected safety findings OBJECTIVES To identify contributing factors associated with inactive disease ( ID ) and clinical remission for patients with juvenile idiopathic arthritis ( JIA ) treated with etanercept .  METHODS Data of an ongoing , long-term , multicentre , prospect i ve , open-label observational study were analysed . Results . A total of 4898 follow-up forms from 787 JIA patients treated with etanercept were evaluated . Sixty-four per cent of the patients were female , 75 % concomitantly received MTX and 45.9 % received corticosteroids . Until the last observation , 47.6 % of patients reached the criteria for ID and 26.6 % achieved the remission on medication criteria . For both , ID and remission on medication , a significant influence of shorter disease duration ( P<0.01 and P<0.001 ) , a weekly dosage of at least 0.8 mg/kg ( P=0.02 ) , lower active joint counts ( P=0.001 ) and lower childhood HAQ score ( P<0.001 and P=0.004 ) at baseline was found . The odds ratio ( OR ) for a girl 's chance to reach ID was 0.73 ( P=0.049 ) and for remission on medication was 0.68 ( P=0.04 ) compared with boys . The concomitant administration of MTX raised the relative chance , especially in patients with seronegative polyarthritis ( OR 2.0 ; P=0.03 ) . CONCLUSION Upon treatment with etanercept , many JIA patients reached ID and remission on medication , although they had suffered from long-st and ing , refractory disease . Earlier initiation of treatment , less severe disease , use of at least the recommended weekly dosage of etanercept , and concomitant treatment with MTX seemed to independently increase the chance for reaching remission . These data should be confirmed by controlled prospect i ve studies Objectives : To evaluate the responsiveness of children with juvenile idiopathic arthritis ( JIA ) to hepatitis B vaccination and to determine the most useful vaccination schedule . Methods : 39 children with JIA were enrolled in the study ; all were in remission and negative to serological testing for hepatitis B surface antigen ( HbsAg ) . The control group consisted of 41 healthy children . There were two different vaccination schedules : group I was vaccinated at 0 , 1 , and 3 months ; group II was vaccinated at 0 , 1 , and 6 months .  Positive responsiveness to the vaccine was defined as an anti-hepatitis B antibody titre above 10 mIU/ml . Results : All the children except one with systemic JIA developed an antibody response . None of the JIA patients experienced a flare up or clinical deterioration related to the vaccination . The antibody levels in children with JIA were significantly lower than in the healthy controls . Comparison of the antibody levels between the two vaccination schedules showed no statistical difference in the controls ; in the JIA subjects the group II schedule result ed in a trend to a greater response than the group I schedule ( p<0.07 ) . Vaccine responsiveness was not influenced by either methotrexate or prednisolone treatment . Conclusions : Children with JIA had an adequate response to hepatitis B vaccination and the response was not affected by immunosuppressive treatment . A vaccination schedule at 0 , 1 , and 6 months seems to be preferable to 0 , 1 , and 3 months Sulphasalazine has been established to be an effective drug for second line treatment of early mild to moderate rheumatoid arthritis . Its application for juvenile chronic arthritis ( JCA ) is limited so far and controversial results for the efficacy of this therapy have been published . We studied the efficacy and tolerance of the sulphasalazine treatment in 32 patients with JCA ( 10 with polyarthritis , 21 with pauciarthritis and 1 with systemic form ) . Our results revealed significant response of the treatment at the end of the 6th month in 24/31 patients ( 77 % ) . In one patient the treatment was discontinued because of transitory neutropenia at the end of the 1st month . No significant difference was observed between the efficacy of the treatment in the polyarticular and pauciarticular disease , as well as newly-diagnosed cases and those with longst and ing disease . From the group of 17 children treated up to the end of the 1st year 88 % achieved complete remission . No serious toxic effects were observed , with the exception of two cases with transitory low- grade neutropenia . According to our results sulphasalazine is an effective and well tolerated drug for second line treatment of JCA- patients To assess health‐related quality of life ( HRQOL ) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis ( JIA ) Objective . The main objective was to determine the 2-year clinical benefit and safety of  etanercept ( ETN ) in children with the juvenile idiopathic arthritis ( JIA ) categories of extended oligoarthritis ( eoJIA ) , enthesitis-related arthritis ( ERA ) , or psoriatic arthritis ( PsA ) . Methods . CLIPPER was a 96-week , phase IIIb , open-label , multicenter study . Patients with eoJIA , ERA , or PsA received ETN 0.8 mg/kg once weekly ( 50 mg max ) for up to 96 weeks . The proportions of patients reaching the JIA American College of Rheumatology ( ACR ) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated . Adverse events ( AE ) were collected throughout the study ( intention-to-treat sample ) . Results . There were 127 patients ( eoJIA n = 60 , ERA n = 38 , PsA n = 29 ) who received ≥ 1 dose of ETN .  The mean disease duration was 31.6 ( eoJIA ) , 23.0 ( ERA ) , and 21.8 ( PsA ) months . At Week 96 , JIA ACR 30/50/70/90/100/inactive disease responses ( 95 % CI ) were achieved by 84.3 % ( 76.7 , 90.1 ) , 83.5 % ( 75.8 , 89.5 ) , 78.7 % ( 70.6 , 85.5 ) , 55.1 % ( 46.0 , 63.9 ) , 45.7 % ( 36.8 , 54.7 ) , and 27.6 % ( 20.0 , 36.2 ) of patients , respectively . The most common AE ( no. events , events per 100 patient-yrs ) overall were headache ( 23 , 10.7 ) , pyrexia ( 12 , 5.6 ) , and diarrhea ( 10 , 4.6 ) . The most common infections were upper respiratory tract infection ( 83 , 38.6 ) , pharyngitis ( 50 , 23.2 ) , gastroenteritis ( 22 , 10.2 ) , bronchitis ( 19 , 8.8 ) , and rhinitis ( 17 , 7.9 ) . No cases of malignancy , active tuberculosis , demyelinating disorders , or death were reported . Conclusion . Over 96 weeks of therapy , ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories , with no major safety issues Adalimumab is a TNF-α blocker antibody similar in structure and function to natural human IgG1 . Even if adalimumab is fully humanized , the development of anti-drug antibodies has been reported in several inflammatory conditions . The objective of our study was to assess the presence of  anti-adalimumab antibodies ( AAA ) and their clinical relevance in a cohort of juvenile idiopathic arthritis ( JIA ) patients on adalimumab . This is a prospect i ve observational cohort study recruiting JIA children . Experiments were performed using a vali date d surface plasmon resonance (SPR)-based optical assay ( Biacore ® T100 ) . Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score with 10 joint count ( JADAS-10 ) . The Mann – Whitney U test , Wilcoxon signed-rank test for paired sample s , chi-square , and Fisher exact test were used to compare data . Pearson ’s and Spearman ’s correlation tests were used to determine correlation coefficients for entered variables : demographic , clinical , and serological data . Ten ( 37 % ) out of 27 patients included in the study had at least one AAA-positive sample . Patients developed AAA between 3 and 38 months after starting adalimumab . Seven ( 70 % ) out of 10 children with AAA positivity experienced at least a relapse compared to 4 ( 23.5 % ) out of 17 AAA-negative children ( rs 0.45 , p < 0.017 ) . In conclusion , using an innovative and accurate assay method , we found a high incidence of anti-drug antibodies in a cohort of adalimumab-treated JIA patients observed over a mean period of 40 weeks ; the presence of anti-adalimumab antibodies seemed to be related to the number of relapses The characterization of the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) properties in pediatric patients is essential in supporting the recommended dosage of canakinumab in the relevant population . Here the PK and PD properties of canakinumab-a monoclonal antibody-in  pediatric patients with systemic juvenile idiopathic arthritis ( SJIA ) are presented . Blood sample s were obtained from 4 phase 2/3 clinical studies in patients with SJIA .  Canakinumab PK properties and total interleukin (IL)-1β kinetic properties were characterized by a population -based PK-binding model . On administration , canakinumab increased total IL-1β complex in SJIA patients . Canakinumab clearance and volume of distribution were not impacted by age in pediatric patients after correction for the patient 's body weight . The estimated serum clearance of canakinumab was 0.106 ± 0.00689 L/day , with a corresponding volume of distribution at steady state of 3.2 L and an estimated half-life of 22 days , based on a model typical body weight of 33 kg . Body-weight-based dosing provided comparable canakinumab exposure across the age groups in patients 2 to < 20 years with SJIA . In younger children , a modest increase in the turnover rate of IL-1β was observed . Compared to other indications , IL-1β production rate was higher and clearance was slower in patients with SJIA . Low immunogenicity incidence of 3.1 % was observed , and none of the patients had neutralizing antibodies . In conclusion , the PK/PD findings further support dose selection of canakinumab in patients with SJIA OBJECTIVES To compare the clinical manifestations of spinal disease , peripheral arthritis and enthesitis , and to evaluate the effectiveness of adalimumab in a large cohort of patients with AS in relation to the presence or absence of psoriasis . METHODS Patients aged > or = 18 years with active AS were enrolled in an open-label study of adalimumab 40 mg every other week . Clinical symptoms were measured at baseline and Week 12 using st and ard assessment criteria . Differences between patients with and those without psoriasis were assessed . The relationship between changes in skin and AS symptoms was also analysed . RESULTS Of 1250 patients with AS who were enrolled in the study , 148 ( 11.8 % ) had a history of psoriasis , including 108 patients with current ( active ) psoriasis at entry . Baseline disease characteristics , including spinal structural damage , peripheral arthritis ( > or = 1 swollen joints ) and enthesitis ( > or = 1 inflamed entheses ) , were similar in both groups . At Week 12 , Assessment of SpondyloArthritis international Society 40 % response was achieved by 46.7 and 54.7 % and Bath AS Disease Activity Index 50 % response by 58.6 and 57.0 % of patients with and without psoriasis , respectively . Median changes in swollen joint scores and Maastricht AS Enthesitis Scores were similar in both groups . Skin changes during adalimumab treatment in AS patients with a history of psoriasis did not correlate with changes in AS symptoms . CONCLUSIONS The presence of psoriasis had no influence on the other clinical manifestations of patients with AS . Treatment with adalimumab markedly improved axial disease , peripheral arthritis and enthesitis , regardless of history of psoriasis OBJECTIVES To evaluate the influence of low-dose MTX and etanercept treatment on efficacy of measles , mumps and rubella ( MMR ) revaccination in children with juvenile idiopathic arthritis . METHODS A prospect i ve nested case-control study was performed to investigate markers of MMR revaccination induced humoral and cell-mediated immunity in 15 patients with juvenile idiopathic arthritis ( ages 6 - 17 yrs ) , treated with either low-dose MTX therapy alone or in combination with etanercept . The control group consisted of 22 healthy children .  Production of IFN-gamma by T memory cells upon in vitro stimulation with measles , mumps and rubella antigens and seroprevalence of virus-specific IgG antibodies were assessed . Medication use , disease activity and patients ' comments on side-effects were observed during the period of 6 months before and after revaccination . RESULTS Low-dose MTX therapy following MMR vaccination proved not to hamper T-cell mediated immunity in vitro . Neither low-dose MTX nor etanercept treatment , given simultaneously with revaccination , markedly interfered with generation of long-lived virus-restricted T cells and protective levels of virus-specific IgG antibodies . No increase in disease activity or medication use was seen within 6 months after MMR revaccination , including JIA patients using etanercept . No overt measles , mumps , rubella or secondary severe infections were noted . CONCLUSIONS Low-dose MTX and etanercept treatment do not seem to interfere with intended outcome of MMR revaccination in children with JIA Objective : To assess the effect of measles , mumps and rubella ( MMR ) vaccination on disease activity in children with juvenile idiopathic arthritis ( JIA ) . Methods : A retrospective observational multicentre cohort study was performed in 314 patients with JIA , born between 1989 and 1996 .  Disease activity and medication use were compared during the period of 6 months before vaccination versus 6 months after vaccination .  Disease activity was measured by joint counts , the Physician ’s global assessment scale and erythrocyte sedimentation rate . Next , we compared disease activity in patients vaccinated between 8 and 9 years of age with the activity in patients who had not been vaccinated at this time ( who received MMR between the ages of 9 and 10 years ) . Results : No increase in disease activity or medication use was seen in the 6 months after MMR vaccination ( n = 207 ) , including in patients using methotrexate ( n = 49 ) . No overt measles infections were noted . When disease activity in vaccinated patients ( n = 108 ) was compared with activity in those not yet vaccinated ( n = 86 ) , there were no significant differences . Conclusions : The MMR booster vaccination does not seem to aggravate disease activity in JIA . This indicates that the most patients with JIA can be vaccinated safely with the MMR vaccine . A prospect i ve study is recommended OBJECTIVE To compare the efficacy and safety of intra-articular triamcinolone hexacetonide ( TH ) and triamcinolone acetonide ( TA ) in children with oligoarticular juvenile idiopathic arthritis ( JIA ) . METHODS One hundred and thirty joints of 85 patients undergoing intra-articular injections were r and omly treated with either TH or TA depending on the availability of the drug . The efficacy of both treatments was evaluated prospect ively in a blinded fashion . A good response was defined as a decrease in the articular score of > or = 60 % from baseline . Clinical , laboratory and immunological variables were noted in order to examine possible factors , other than treatment , predictive of the result . RESULTS Seventy injections were performed using TH and 60 with TA . The two groups were comparable for clinical , immunological and laboratory characteristics . The rate of response was significantly higher with TH than with TA : 81.4 % vs 53.3 % ( P = 0.001 ) at 6 months , 67.1 vs 43.3 % ( P = 0.006 ) at 12 months , and 60 vs 33.3 % ( P = 0.002 ) at 24 months . CONCLUSION At comparable doses TH appeared to be much more effective than TA for intra-articular use , in both short- and long-term follow-up . This result was not affected by disease duration or degree of local and systemic inflammation OBJECTIVES To examine the change in health-related quality of life ( HRQOL ) and its determinants in children with juvenile idiopathic arthritis ( JIA ) treated with methotrexate ( MTX ) .  METHODS Patients were extracted from the PRINTO clinical trial which aim ed to evaluate the efficacy and safety profile of MTX administered in st and ard , intermediate or higher doses ( 10 , 15 and 30 mg/m(2)/week respectively ) . Children with polyarticular-course JIA , who were less than 18 years and had a complete HRQOL assessment were included . RESULTS A total of 521 children were included . At baseline , patients with JIA showed poorer HRQOL ( p<0.01 ) than healthy children . In 207/412 ( 50 % ) and 63 ( 15 % ) children , HRQOL values were 2 st and ard deviations below the mean of healthy controls in the physical and psychosocial summary scale , respectively . After 6 months of treatment with st and ard dose MTX , there was a statistically significant improvement in all HRQOL health concepts , particularly the physical ones . Similar improvements were observed in those who did not respond to a st and ard dose of MTX and were subsequently r and omised to a higher dose . The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with st and ard dose MTX . Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation , pain intensity and an antinuclear-antibody-negative status . CONCLUSIONS MTX treatment produces a significant improvement across a wide range of HRQOL components , particularly in the physical domains , in patients with JIA OBJECTIVE To determine the long-term safety and efficacy of rilonacept , an anti-interleukin-1 fusion protein , in patients with active systemic juvenile idiopathic arthritis ( JIA ) . METHODS In patients with systemic JIA , ages 4 - 20 years , the efficacy of rilonacept was evaluated using 30 % , 50 % , and 70 % levels of improvement according to the adapted American College of Rheumatology ( ACR ) Pediatric 30 , 50 , and 70 response criteria , respectively . Efficacy and safety were evaluated during 23 months of open-label treatment ( 3 phases ) after a 4-week , double-blind , placebo-controlled phase . Following double-blind treatment with 2.2 mg/kg or 4.4 mg/kg of rilonacept , patients were eligible to receive open-label treatment at their prior dose , with adjustments . Reductions in the median daily dose of oral prednisone and improvements in laboratory parameters of disease activity ( i.e. , decreased levels of D-dimer and myeloid-related proteins [ MRPs ] ) were also evaluated . RESULTS Twenty-four patients entered the double-blind study and 23 entered the open-label period . Patients were predominantly white and female , and had a median age of 14.0 years at baseline . No significant differences in efficacy were observed between the rilonacept- and placebo-treated patients during the double-blind phase , but fever and rash completely resolved by month 3 in all patients during the open-label treatment period and did not recur . Adapted ACR Pediatric 30 , 50 , and 70 response rates at 3 months from the start of the study were 78.3 % , 60.9 % , and 34.8 % , respectively ; these responses were generally maintained over the study duration . Levels of D-dimer and MRP-8/MRP-14 dramatically improved during the study , and in 22 of 23 patients , the prednisone dose was decreased or prednisone therapy was discontinued . No serious treatment-related adverse events were observed . CONCLUSION Sustained improvements in clinical and laboratory measures of the articular and systemic manifestations of systemic JIA were achieved in > 50 % of rilonacept-treated patients over 2 years . Treatment with rilonacept had a substantial steroid-sparing effect and was generally well-tolerated OBJECTIVE To assess dosing , preliminary safety , and efficacy of canakinumab , a fully human anti-interleukin-1β ( anti-IL-1β ) antibody , in children with systemic juvenile idiopathic arthritis ( JIA ) and active systemic features . METHODS In this phase II , multicenter , open-label , dosage-escalation study , children with systemic JIA who were ≥4 years of age , had fever , and were receiving ≤0.4 mg/kg/day of corticosteroids  were administered a single subcutaneous dose of canakinumab , 0.5 - 9 mg/kg of body weight , and were redosed upon relapse . Response to treatment was assessed according to an adaptation of the American College of Rheumatology ( ACR ) pediatric criteria for improvement . RESULTS A total of 23 children ages 4 - 19 years with active disease were enrolled . Of these , 1 patient was excluded from analysis , and 3 of the reenrolled patients were included twice in the efficacy analysis . By day 15 of the first treatment cycle , 15 of 25 patients ( 60 % ) had achieved an adapted ACR Pediatric 50 response , with 4 of them achieving inactive disease status . Response was sustained over time , with 11 of 13 patients able to maintain their response throughout the study . In 8 of the 11 responders who had been receiving steroids at baseline , the steroid dosage was decreased from a mean of 0.38 mg/kg/day to 0.13 mg/kg/day over the first 5 months , and 4 of them were able to discontinue steroids . At a dose of 4 mg/kg of canakinumab given subcutaneously every 4 weeks , the median percentage of patients predicted to relapse within 4 weeks was estimated to be 6 % ( 95 % confidence interval 1 - 21 ) . Therapy was generally well tolerated and few patients experienced injection-site reactions . CONCLUSION Canakinumab  has a promising preliminary safety and efficacy profile in this limited cohort . Based on the findings of this trial , further studies in a larger population of children with systemic JIA are warranted OBJECTIVE To determine the prevalence of temporom and ibular joint ( TMJ ) disease in a cohort of children with new-onset juvenile idiopathic arthritis ( JIA ) , and to compare magnetic resonance imaging ( MRI ) with ultrasound ( US ) for the detection of acute and chronic changes of TMJ arthritis . METHODS Between January 2005 and April 2007 , children with newly diagnosed JIA were prospect ively evaluated for TMJ arthritis . Prior to imaging , jaw pain and disability were assessed with question naires and physical examination . The TMJs of all patients were imaged with MRI and US within 8 weeks of diagnosis . RESULTS Of the 32 patients enrolled , 78 % were female , and the median age was 8.6 years ( range 1.5 - 17.2 years ) .  Acute TMJ arthritis was diagnosed in 75 % of the children by MRI and in none by US ; chronic arthritis was diagnosed in 69 % by MRI and in 28 % by US . Findings of both acute and chronic TMJ disease were detected by MRI in 53 % of the patients . Of those with acute TMJ arthritis , 71 % were asymptomatic , and 63 % had normal findings on jaw examination . Fifty-six percent of patients with acute disease had an improved maximal incisal opening after corticosteroid injection . Among these responders , 56 % had been asymptomatic and had normal jaw examination findings . CONCLUSION TMJ arthritis was present in the majority of patients with new-onset JIA . Findings on MRI along with responses to treatment among asymptomatic patients with normal jaw examination findings suggest that a history review and physical examination are not sufficient to screen for TMJ disease . Our results also suggest that MRI and US findings are not well correlated , and that MRI is preferable for the detection of TMJ disease in new-onset JIA Objective . To assess the longterm safety and effectiveness of tocilizumab ( TCZ ) in systemic-onset juvenile idiopathic arthritis ( sJIA ) . Methods . The longterm extension phase of 2 pivotal studies ( phase II with 11 patients and phase III with 56 patients ) in patients with active sJIA was analyzed . Patients received open-label TCZ ( 8 mg/kg , every 2 weeks ) without concomitant use of disease-modifying antirheumatic drugs . Results . In total , 67 patients were enrolled . All patients received corticosteroid at baseline . Median duration of exposure to TCZ was 3.4 years . Nine patients withdrew from the study [ 4 because of adverse events ( AE ) , 4 because of the development of anti-TCZ antibodies , and 1 because of inadequate response ]  . Rates of AE and serious AE were 803.7/100 patient-years ( PY ) and 34.7/100 PY , respectively . The most common serious AE were infections ( 13.2/100 PY ) . No cases of malignancy or death were reported . Two serious infusion reactions were reported in patients testing negative for anti-TCZ antibodies . One definite macrophage activation syndrome ( MAS ) case and 1 potential MAS case were identified . American College of Rheumatology ( ACR ) response rates attained early in the TCZ treatment period were maintained throughout the study : at Week 168 , JIA ACR 30 , 50 , 70 , 90 , and 100 response rates were 80.3 % , 80.3 % , 75.4 % , 60.7 % , and 18.0 % , respectively . In total , 22 of 67 patients ( 32.8 % ) completely discontinued corticosteroids without flare . Conclusion . TCZ has demonstrated durability of effectiveness in the longterm treatment of children with sJIA and has shown good tolerability and a low discontinuation rate associated with AE , development of anti-TCZ antibodies , or inadequate response . ( Clinical Trials.gov NCT00144599 and NCT00144612 ) . ( First Release March 15 2014 ; J Rheumatol 2014;41:759 - 67 ; doi:10.3899/jrheum.130690 BACKGROUND Systemic juvenile idiopathic arthritis ( JIA ) is the most severe subtype of JIA ; treatment options are limited . Interleukin-6 plays a pathogenic role in systemic JIA . METHODS We r and omly assigned 112 children , 2 to 17 years of age , with active systemic JIA ( duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids ) to the anti-interleukin-6 receptor antibody tocilizumab  ( at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was < 30 kg ) or placebo given intravenously every 2 weeks during the 12-week , double-blind phase . Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab . All patients could enter an open-label extension . RESULTS At week 12 , the primary end point ( an absence of fever and an improvement of 30 % or more on at least three of the six variables in the American College of Rheumatology [ ACR ] core set for JIA , with no more than one variable worsening by more than 30 % ) was met in significantly more patients in the tocilizumab group than in the placebo group ( 64 of 75 [ 85 % ] vs. 9 of 37 [ 24 % ] , P<0.001 ) . At week 52 , 80 % of the patients who received tocilizumab had at least 70 % improvement with no fever , including 59 % who had 90 % improvement ; in addition , 48 % of the patients had no joints with active arthritis , and 52 % had discontinued oral glucocorticoids . In the double-blind phase , 159 adverse events , including 60 infections ( 2 serious ) , occurred in the tocilizumab group , as compared with 38 , including 15 infections , in the placebo group . In the double-blind and extension periods combined , 39 serious adverse events ( 0.25 per patient-year ) , including 18 serious infections ( 0.11 per patient-year ) , occurred in patients who received tocilizumab . Neutropenia developed in 19 patients ( 17 patients with grade 3 and 2 patients with grade 4 ) , and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range . CONCLUSIONS Tocilizumab was efficacious in severe , persistent systemic JIA . Adverse events were common and included infection , neutropenia , and increased aminotransferase levels . ( Funded by Hoffmann-La Roche ; Clinical Trials.gov number , NCT00642460 . ) OBJECTIVE The Childhood Health Assessment Question naire ( CHAQ ) , Juvenile Arthritis Functional Assessment Report ( JAFAR ) , and Juvenile Arthritis Functional Status Index ( JASI ) are widely used functional measures for juvenile idiopathic arthritis ( JIA ) that differ in content , format , and completion time . We compared the responsiveness and child-parent agreement of the JAFAR , CHAQ , and JASI in a prospect i ve , multicenter study . METHODS Children and adolescents from 5 rheumatology centers were enrolled . Subjects were about to undergo therapy ( intraarticular corticosteroid injections [ IAS ] and methotrexate or hip surgery ( MTX/hip ] ) expected to produce a functional improvement . All subjects were studied before the intervention and at 6 weeks and 6 months posttreatment . At each study visit , the 3 measures were administered in r and omized , balanced order to both parents and children . RESULTS A total of 92 subjects ( mean age 12.8 years ) were enrolled in the study , 74 of which were in the IAS group . The responsiveness of all 3 measures was moderate to strong . The st and ardized response mean at 6 weeks for the IAS group on the JAFAR , CHAQ , and JASI was 0.41 ( 95 % confidence interval [ 95 % CI ] 0.18 , 0.64 ) , 0.70 ( 95 % CI 0.47 , 0.93 ) , and 0.36 ( 95 % CI 0.13 , 0.59 ) , respectively . The CHAQ was somewhat more responsive to change at 6 weeks ( IAS group : relative efficiency 0.34 [ JAFAR ] , 0.27 [ JASI ] ) , but less responsive at 6 months ( MTX/hip group : relative efficiency 5.1 [ JAFAR ] , 3.9 [ JASI ] ) . All 3 question naires showed acceptable parent-child agreement , and overall , there were few differences between the 3 question naires . CONCLUSION The functional outcome measures currently used for JIA are all adequately responsive for use in trials or in the clinic setting . The choice of which measure to use should therefore be based on the time available for completion , the intended clinical / research use , and the depth of content required Background Children with arthritis may endure a lifetime of disfigurement , dysfunction , and pain if acute inflammation progresses to chronic changes in the joint cartilage and underlying bone . Intraarticular steroids have become an integral component of treatment , but at times are difficult to deliver to joints , such as the subtalar joint , that have complex anatomies . Objective We describe our technique and outcomes using fluoroscopically guided intraarticular subtalar steroid injection in patients with active symptoms of juvenile idiopathic arthritis ( JIA ) . Material s and methods Fluoroscopically guided subtalar joint injections were performed in 38 children ( mean age 6.7 years ) . Medical records were review ed retrospectively and improvement was evaluated clinical ly by the degree of foot movement in eversion and inversion . Results Subtalar joint injection was technically successful in 100 % of the JIA patients with improvement in physical symptoms in 34/38 ( 89 % ) . Of the 38 children , 32 were followed up within 13 weeks of the initial injection and , therefore , satisfied the eligibility criteria for resolution of arthritis . Of these 32 children , 14 showed clinical resolution ( 44 % ) . The mean duration of improvement was 1.2 ± 0.9 years . Children with a longer interval ( > 1 year ) from diagnosis to treatment had significantly less resolution ( P = 0.04 ) . Local subcutaneous atrophy or hypopigmentation were observed in 53 % of the children after steroid injection ( 20/38 ) . These minor complications were associated with a greater volume of steroid injected into the site per child ( P = 0.02 ) . Conclusion Fluoroscopically guided subtalar joint injection is an effective treatment for subtalar arthropathy . Prompt referral for intraarticular steroid treatment in the acute phase improves response . Skin changes often occur at the injection site , and specific pre caution s should be employed to reduce this risk . Prospect i ve study is indicated to determine the most effective treatment strategy to prevent long-term pain and disability OBJECTIVE To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis ( JIA ) in order to identify patients who will develop bone mass reductions . METHODS We conducted a prospect i ve cohort study of 108 children with early JIA ( ages 6 - 18 years ; mean disease duration 19.3 months ) who were individually matched with 108 healthy children for age , sex , race , and county of residence .  Bone mass and changes in total body , spine , femur , and forearm bone mineral density and bone mineral content ( BMC ) , body composition , growth , and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later . Low bone mass was defined as a Z score > 1 SD below the reference population . RESULTS Of the 200 children evaluated at followup , the 100 healthy children had greater gains in total body BMC ( P = 0.035 ) , distal radius BMC ( P < 0.001 ) , and total body lean mass ( P < 0.001 ) than did the 100 JIA patients . Low or very low total body BMC was observed in 24 % of the patients and 12 % of the healthy children . Bone formation , bone resorption , and weight-bearing activities were reduced in the patients compared with the healthy children . Multiple regression analysis showed that in patients with JIA , serum bone-specific alkaline phosphatase , serum C-telopeptide of type I collagen , and weight-bearing activities were independent predictors of changes in total body BMC . Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset . CONCLUSION Patients with JIA have moderate reductions in bone mass gains , bone turnover , and total body lean mass early in the disease course OBJECTIVE Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide ( TA ) is equivalent to that of triamcinolone hexacetonide ( TH ) , if used at double the dosage . In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints , in children with juvenile idiopathic arthritis ( JIA ) . METHOD Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study . The symmetry was assessed by both clinical examination and synovial fluid analysis . The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA . The identity of injected compound was blinded to the patient and to the physician . RESULTS Thirty-seven patients , 30 female , seven male , with JIA , entered the study . A total of 86 joints were injected . Twenty-one ( 53.8 % ) of the joints injected with TA  relapsed first compared with only six ( 15.4 % ) of the joints injected with TH . In three ( 7.7 % ) relapse occurred simultaneously . Nine ( 23 % ) were still in remission after 24-month follow-up . The percentage of joints with lasting remission was higher with TH than with TA ( 80 vs 47.5 % after 12 months and 63.6 vs 32.4 % after 24 months , respectively ; log rank test P = 0.003 ) . CONCLUSION Even when TA is given at higher doses , TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA OBJECTIVES Etanercept , a recombinant TNF receptor fusion protein , has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years . In adult patients , efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly . Therefore , safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c . was evaluated in a 3 month open label trial . METHODS Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial . Active polyarticular disease was defined by the presence of five or more active joints with swelling , alternatively with pain or tenderness combined with limitation of motion . Safety assessment s were based on adverse events ( AEs ) reports . Efficacy was assessed using the PedACR30/50/70 criteria . RESULTS At the start of treatment the patients showed high disease activity . A rapid reduction of all disease activity parameters was observed . A PedACR30/50/70 response was reached by 75%/35%/10 % of patients after 4 weeks , 90%/75%/35 % after 8 weeks and 95%/75%/75 % after 12 weeks of treatment . There were 37 AEs , none of them serious , with injection site reactions and minor infections being the most frequent . There was no drop out . Long-term follow-up of the patients will be carried out in the German JIA Registry . CONCLUSION Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated The aim of this 12-month prospect i ve study was to compare reports describing the health-related quality of life ( HRQL ) of children with Juvenile idiopathic arthritis ( JIA ) obtained from parents and children , to investigate the extent to which the children ’s HRQL changed over a 12-month period , and to describe the relationship between children ’s HRQL , and their experience of pain and use of pain coping strategies . Fifty-four children aged 8–18 years with JIA and their parents completed st and ard question naires assessing children ’s HRQL , pain intensity , and pain coping strategies at baseline , 6 months , and 12 months . In general , children reported that their HRQL was better than was reported by parents . Both informants described children ’s HRQL as being very stable over the 12 months of the study . Consistent with the Biobehavioural Model of Pain , there was a significant negative relationship between children ’s HRQL and their experience of pain . However , there was little evidence that pain coping strategies mediated the relationship between children ’s experience of pain and their HRQL OBJECTIVE To develop preliminary criteria for inactive disease and clinical remission for select categories of juvenile idiopathic arthritis ( JIA ) , and to decide what such clinical states should predict in terms of probability of disease recurrence . METHODS A Delphi serial question naire consensus-formation approach was used initially to gather criteria in use by pediatric rheumatologists ( PR ) for defining clinical remission in oligoarticular ( persistent and extended ) , rheumatoid factor ( RF ) positive and negative polyarticular , and systemic JIA . Results from sequential question naires provided an agenda for a nominal group technique ( NGT ) conference to reach consensus on unresolved questions . RESULTS One hundred and thirty PR from 34 countries responded to the question naires and 20 PR from 9 countries attended the conference . Draft criteria for inactive disease include the following : no active arthritis ; no fever , rash , serositis , splenomegaly , or generalized lymphadenopathy attributable to JIA ; no active uveitis ; normal erythrocyte sedimentation rate or C-reactive protein ; and a physician 's global assessment of disease activity rated at the best score possible for the instrument used . According to consensus vote , 6 continuous months of inactive disease on medication defines clinical remission on medication , while 12 months of inactive disease off all anti-arthritis ( and anti-uveitis ) medications defines clinical remission off medication . The finalized criteria for remission off medication ideally should predict that a patient has < /= 20 % probability of disease recurrence within the next 5 years . CONCLUSION Using consensus formation techniques , we formulated preliminary criteria for inactive disease and clinical remission on and off medication for use in select categories of JIA . Retrospective validation is in progress ; prospect i ve validation will follow . Future efforts will include other categories of JIA Objectives Pain is a very common symptom of juvenile idiopathic arthritis ( JIA ) . Disease activity alone can not explain symptoms of pain in all children , suggesting other factors may be relevant . The objectives of this study were to describe the different patterns of pain experienced over time in children with JIA and to identify predictors of which children are likely to experience ongoing pain . Methods This study used  longitudinal- data from patients ( aged 1–16 years ) with new-onset JIA .  Baseline and up to 5-year follow-up pain data from the Childhood Arthritis Prospect i ve Study ( CAPS ) were used . A two-step approach was adopted . First ,  pain trajectories  were modelled using a discrete mixture model . Second , multinomial logistic regression was used to determine the association between variables and trajectories . Results Data from 851 individuals were included ( 4 years , median follow-up ) . A three-group trajectory model was identified : consistently low pain ( n=453 ) , improved pain ( n=254 ) and consistently high pain ( n=144 ) . Children with improved pain or consistently high pain differed on average at baseline from consistently low pain . Older age at onset , poor function/disability and longer disease duration at baseline were associated with consistently high pain compared with consistently low pain . Early increases in pain and poor function/disability were also associated with consistently high pain compared with consistently low pain . Conclusions This study has identified routinely collected clinical factors , which may indicate those individuals with JIA at risk of poor pain outcomes earlier in disease . Identifying those at highest risk of poor pain outcomes at disease onset may enable targeted pain management strategies to be implemented early in disease thus reducing the risk of poor pain outcomes Objectives : To assess the vaccine response in juvenile idiopathic arthritis ( JIA ) as an extension of previous observation of immunogenicity and safety of a non-adjuvanted influenza A H1N1/2009 vaccine in a large population of juvenile rheumatic diseases . Moreover , to assess the possible influence of demographic data , disease subtypes , disease activity , and treatment on immunogenicity and the potential deleterious effect of the vaccine in the disease itself , particularly in the number of arthritis and inflammatory markers . Methods : A total of 95 patients with JIA and 91 healthy controls were evaluated before and 21 days after vaccination , and serology for anti-H1N1 was performed by haemagglutination inhibition assay ( HIA ) .  Patient and physician  visual analogue scales ( VAS ) , Childhood Health Assessment Question naire ( CHAQ ) , number of active joints , acute phase reactants , and treatments were evaluated before and after vaccination . Adverse events were also reported . Results : JIA patients and controls were comparable regarding mean current age ( 14.9 ± 3.2 vs. 14.6 ± 3.7 years , p = 0.182 ) . After vaccination , the seroconversion rate was significantly lower in JIA patients compared to controls ( 83.2 % vs. 95.6 % , p = 0.008 ) , particularly in the polyarticular subtype ( 80 % vs. 95.6 % , p = 0.0098 ) . Of note , JIA subtypes , number of active joints , acute phase reactants , CHAQ , patient and physician VAS , and use of disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive drugs were similar between seroconverted and non-seroconverted patients ( p > 0.05 ) . Regarding vaccine safety , no deterioration was observed in the number of active joints and acute phase reactants during the study period . Conclusion : Influenza A H1N1/2009 vaccination in JIA induces a lower but effective protective antibody response probably independent of disease parameters and treatment with an adequate disease safety profile Tumor necrosis factor-alpha ( TNF-α ) inhibitors are effective treatment for juvenile idiopathic arthritis ( JIA ) but may increase infection rates . However , active JIA may also render patients vulnerable to infection . In this study , we prospect ively assessed infection rates in JIA patients treated with and without TNF-α inhibitors  and correlated disease activity with infection risk .  TNF-α inhibitor-naïve JIA subjects were followed up for 12 months . Subjects initiated on TNF-α inhibitors after enrollment were analyzed in the TNF group . Subjects treated without TNF-α inhibitors were analyzed in the non-TNF group . Question naires captured mild or severe infections . JIA disease activity by Childhood Health Assessment Question naire ( CHAQ ) disability index/pain score and physician joint count/global assessment was recorded . Twenty TNF and 36 non-TNF subjects were analyzed .  The total infection rate ratio for TNF versus non-TNF group subjects was 1.14 ( 95 % CI , 0.78–1.66 ; p = 0.51 ) . The average rate of infections per month was 0.29 for TNF and 0.24 for non-TNF subjects . No severe infections or hospitalizations occurred in either group . Secondary infectious outcomes were also similar between groups . Controlling for study group , an increase in CHAQ pain score correlated with an increase in several infectious outcome measures . Our results suggest no difference in infection rates between JIA subjects treated with and without TNF-α inhibitors . Additionally , JIA disease activity may have contributed to infection risk in our cohort , irrespective of immunosuppressive therapy . Future analysis of the relationship between treatment regimens , disease activity , and infection rates may help to further delineate predictors of infection risk in JIA patients Objective . Pain and reduced physical activity levels are common in children with juvenile idiopathic arthritis ( JIA ) . Currently , there is no consensus about the role of physical activity in managing pain in JIA . The purpose of our study was to assess the relationship between physical activity level and pain in children ages 11 to 18 years with JIA . Methods . A r and om sample of 50 patients with JIA were approached by mailed question naires . Physical activity was determined using the Physical Activity Question naire ( PAQ ) .  Pain measures included the Numerical Rating Scale ( pain severity ) , SUPER-KIDZ body diagram ( number of painful areas ) , and the Child Activities Limitations Inventory-21 ( pain interference ) . Generalized linear models were used to assess the relationship between physical activity and pain , as well as the roles of sex and age . Results . The response rate was 84 % . Thirty-four respondents completed the question naire package . The median age was 15 years . The mean PAQ score was 2.16/5 . Physical activity declines with increasing age in youth with JIA ( r = 0.53 , p = 0.0014 ) . Lower physical activity is associated with greater pain interference ( r = 0.39 , p = 0.0217 ) and more severe pain ( r = 0.35 , p = 0.0422 ) . Conclusion . Children with JIA report significantly less activity than healthy children based on PAQ scores , with physical activity declining throughout adolescence . Physical activity is inversely related to pain interference and severity in children with JIA . Our findings suggest that physical activity interventions may play an important role in the management of pain in JIA OBJECTIVE To 1 ) assess the safety and feasibility of laboratory-based exercise testing in juvenile idiopathic arthritis ( JIA ) , 2 ) test the safety and feasibility of a 3-month exercise program in JIA , 3 ) assess pain during exercise in JIA , 4 ) compare ratings of perceived effort ( RPE ) with heart rate ( HR ) achieved , and 5 ) estimate the training effect on metabolic efficiency of gait as measured by submaximal exercise testing . METHODS Nine children with JIA were enrolled in a 12-week circuit training program involving pool , stationary bicycle , treadmill , and Fitball . They underwent formal exercise testing before and after the program , underwent a full joint assessment , were administered the Childhood Health Assessment Question naire and Juvenile Arthritis Functional Status Index , and were assessed for overall quality of life and health-related quality of life . A visual analog scale was used to assess pain during testing and training , and the Borg scale was used to measure RPE . RESULTS Children with JIA were able to participate in exercise testing without any significant problems . Children with severe hip disease dropped out of the exercise program due to  pain  during the exercise sessions and worsened arthritis symptoms . Target HR was achieved and correlated with RPE in the bicycle and treadmill sessions . Submaximal exercise testing showed an improvement with a small to moderate effect size . CONCLUSION This study suggests that it is safe , feasible , and acceptable for children with arthritis , in the absence of severe hip involvement , to participate in formal exercise testing and structured fitness programs OBJECTIVES The purpose of this study was to determine the potential of high-resolution ultrasonography for the detection of temporom and ibular joint ( TMJ ) changes in children with juvenile idiopathic arthritis ( JIA ) . METHODS We investigated prospect ively 20 children ( 17 female and 3 male ; mean age 11.06 years , st and ard deviation 3.43 years ) with TMJ disorders caused by JIA , over a period of 16 months . Using a 12 MHz array transducer , four images in each TMJ ( 160 images ) were acquired . Each image was analysed with regard to five different aspects ( condylar erosion , thickness of the condylar disc , synovial thickness , joint effusion and enlargement of the intra-articular space ) . RESULTS Diagnosis of JIA was ensured for every child and involvement of the TMJ was proven by MRI . Overall 287 changes ( 35.9 % ) were detected by using high-resolution ultrasonography . On 124 images ( 77.5 % ) condylar erosions were diagnosed ; on 55 images ( 34.4 % ) synovial thickness was abnormal ; on 48 images ( 30 % ) we could see higher thickness of the condylar disc ; on 40 images ( 25 % ) irregularities of the bony surface were detected ; and on 20 images ( 12.5 % ) we found joint effusion . CONCLUSION High-resolution ultrasonography could be a sufficient diagnostic method , especially for the detection of condylar involvement in children with JIA , even if not all parts of the TMJ are visible for ultrasonography . High-resolution ultrasonography is a valuable tool in particular situations : ( i ) when MRI examination is not available ; ( ii ) when children fear MRI examination ; ( iii ) in more advanced stages of JIA ; and ( iv ) for monitoring the progression of TMJ involvement and response of therapy The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis ( JIA ) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period , a 6‐month double‐blind withdrawal period , and a long‐term extension ( LTE ) phase . The aim of this study was to present the safety , efficacy , and patient‐reported outcomes  of abatacept treatment ( 10 mg/kg every 4 weeks ) during the LTE phase , for up to 7 years of followup OBJECTIVES Hepatitis B is a vaccine preventable disease with intermediate endemicity in Greece . Patients with juvenile idiopathic arthritis ( JIA ) on immunomodulating therapy  are prone to infection or reactivation of hepatitis B virus ( HBV ) . The aim of this study is to define the immune status against HBV in children newly-diagnosed with JIA . METHODS Case-control prospect i ve study including 89 JIA patients and 89 controls matched for age and gender . Eighty-nine JIA patients were included in the study ( 22 males ) , with a mean age of 6.8 years . Sera were tested for hepatitis B surface antigen , hepatitis B core antibody , and anti-HBs . Patients with anti-HBs titers ≥10 IU/L were considered immune . Data were analysed with SPSS 18.0 version . RESULTS In the JIA group 55 % were HBV immune ( anti-HBs level ≥10 IU/L ) while in the control group 92 % were immune against HBV ( p<0.001 ) . Antibody levels in the patient group were significantly lower compared to the control group . The mean concentration of anti-HBs levels in JIA patients was 18.3 IU/L versus 82.6 IU/L in the control group ( p<0.001 ) . CONCLUSIONS Antibody titers against HBV in fully vaccinated JIA patients due to start treatment are significantly lower compared to matched healthy children in this study . Diagnosis of JIA and older age were associated with the absence of protective antibodies . Although there is no evidence to support the introduction of a booster HBV dose in healthy children who mount low antibody response following immunisation , further studies are required to address this question in patients with JIA OBJECTIVE We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis ( JIA ) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade . Here , we report results from the long-term extension ( LTE ) phase of that study . METHODS This report describes the long-term , open-label extension phase of a double-blind , r and omized , controlled withdrawal trial in 190 patients with JIA ages 6 - 17 years . Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks , with or without methotrexate . Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect > or=21 months ( 589 days ) of treatment . Safety results include all available open-label data as of May 7 , 2008 . RESULTS Of the 190 enrolled patients , 153 entered the LTE . By day 589 , 90 % , 88 % , 75 % , 57 % , and 39 % of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology ( ACR ) Pediatric 30 ( Pedi 30 ) , Pedi 50 , Pedi 70 , Pedi 90 , and Pedi 100 criteria for improvement , respectively . Similar response rates were observed by day 589 among patients previously treated with placebo . Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE , 73 % , 64 % , 46 % , 18 % , and 5 % achieved ACR Pedi 30 , Pedi 50 , Pedi 70 , Pedi 90 , and Pedi 100 responses , respectively , by day 589 of the LTE . No cases of tuberculosis and no malignancies were reported during the LTE . Pneumonia developed in 3 patients , and multiple sclerosis developed in 1 patient . CONCLUSION Abatacept provided clinical ly significant and durable efficacy in patients with JIA , including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase Objective . To compare child  self-report and parent/proxy report of health-related quality of life ( HRQOL ) , disability , and fatigue in children with active polyarticular juvenile idiopathic arthritis ( JIA ) to that of children with inactive polyarticular JIA and to previous data from healthy controls . Methods . Cross-sectional survey of children with polyarticular JIA diagnosed and treated between 2000 to 2006 and their parent/proxy . The Childhood Health Assessment Question naire , Pediatric Quality of Life Inventory ( PedsQL ) Generic Core Scales , PedsQL Rheumatology Module , and PedsQL Multidimensional Fatigue Scale were administered . Disease activity data were collected from the physician clinic notes . Comparisons were performed with t tests . Correlations between patient and parent/proxy reports were measured with Pearson correlation coefficients . Results . Sixty children and /or their parents/proxies participated ( 79 % response rate ) . Disease activity status was available for 52 , and 32 met criteria for inactive disease ( 62 % ) . Participants reported lower scores on the PedsQL Generic Core Scales ( range 2.54–9.13 points lower ) and the PedsQL Rheumatology Module ( range 2.46–6.96 points lower ) than those with inactive disease . Participants also reported lower scores on the PedsQL Multidimensional Fatigue Scale than did healthy controls , regardless of disease activity status ( range 0.06–9.2 points lower ) . Conclusion . Although children in this cohort with polyarticular JIA and inactive disease reported HRQOL scores similar to those of healthy controls , children with polyarticular JIA and their parents/proxies tended to report more fatigue than controls , regardless of disease activity . Application of these measures prospect ively to larger cohorts of children with JIA is needed to assess these differences
Good disease control , with therapeutic escalation to achieve low disease activity , was recommended .
OBJECTIVE To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis , sacroiliitis , or enthesitis .