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
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
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 .