title: Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial 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 Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial. 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 Effects of an eight-week physical conditioning program on disease signs and symptoms in children with chronic arthritis. Long‐Term Safety, Efficacy, and Quality of Life in Patients With Juvenile Idiopathic Arthritis Treated With Intravenous Abatacept for Up to Seven Years Comparison of intra-articular triamcinolone hexacetonide and triamcinolone acetonide in oligoarticular juvenile idiopathic arthritis. Head-to-head, randomised, crossover study of oral versus subcutaneous methotrexate in patients with rheumatoid arthritis: drug-exposure limitations of oral methotrexate at doses ≥15 mg may be overcome with subcutaneous administration Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry Ankylosing spondylitis: what is the optimum duration of a clinical study? A one year versus a 6 weeks non-steroidal anti-inflammatory drug trial. Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Methotrexate efficacy, but not its intolerance, is associated with the dose and route of administration Leflunomide or methotrexate for juvenile rheumatoid arthritis. Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group. Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis. Long-term outcome of patients with JIA treated with etanercept, results of the biologic register JuMBO. A Randomized, Double‐Blind, Placebo‐Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis‐Related Arthritis Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis. Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial. Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: results of a multicentre, double-blind, randomised-withdrawal trial Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE–JIA): a multicentre randomised open-label clinical trial Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Preliminary definition of improvement in juvenile arthritis. Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national Arthritis and Biologics in Children Register Oral versus intramuscular methotrexate in juvenile chronic arthritis. Italian Pediatric Rheumatology Study Group. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Pain, stiffness, and fatigue in juvenile polyarticular arthritis: contemporaneous stressful events and mood as predictors. Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA) A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. Efficacy of methotrexate in ankylosing spondylitis: a randomized, double blind, placebo controlled trial. Daily pain and symptoms in children with polyarticular arthritis. Pain relief in the rheumatoid knee after steroid injection. A single-blind comparison of hydrocortisone succinate, and triamcinolone acetonide or hexacetonide. Effect of Electromyographic Biofeedback Training on Pain, Quadriceps Muscle Strength, and Functional Ability in Juvenile Rheumatoid Arthritis No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial Health-Related Quality of Life, Physical Function, Fatigue, and Disease Activity in Children with Established Polyarticular Juvenile Idiopathic Arthritis 2.3 Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular course juvenile rheumatoid arthritis (JRA): Findings from an open-label treatment extension Clinical relevance of C-reactive protein in ankylosing spondylitis and evaluation of the NSAIDs/coxibs' treatment effect on C-reactive protein. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis.
abstract: Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis ( pcJIA ) . Methods This three-part , r and omised , placebo-controlled , double-blind withdrawal study ( NCT00988221 ) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate .  During part 1 , patients received open-label tocilizumab every 4 weeks ( 8 or 10 mg/kg for body weight ( BW ) < 30 kg ; 8 mg/kg for BW ≥30 kg ) . At week 16 , patients with ≥JIA-American College of Rheumatology ( ACR ) 30 improvement entered the 24-week , double-blind part 2 after r and omisation 1:1 to placebo or tocilizumab ( stratified by methotrexate and steroid background therapy ) for evaluation of the primary end point : JIA flare , compared with week 16 . Patients flaring or completing part 2 received open-label tocilizumab . Results In part 1 , 188 patients received tocilizumab  ( < 30 kg : 10 mg/kg ( n=35 ) or 8 mg/kg ( n=34 ) ; ≥30 kg : n=119 ) . In part 2 , 163 patients  received tocilizumab ( n=82 ) or placebo ( n=81 ) . JIA flare occurred in 48.1 % of patients on placebo versus 25.6 % continuing tocilizumab ( difference in means adjusted for stratification : −0.21 ; 95 % CI −0.35 to −0.08 ; p=0.0024 ) . At the end of part 2 , 64.6 % and 45.1 % of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses , respectively . Rates/100 patient-years ( PY ) of adverse events ( AEs ) and serious AEs ( SAEs ) were 480 and 12.5 , respectively ; infections were the most common SAE ( 4.9/100 PY ) . Conclusions Tocilizumab treatment results in significant improvement , maintained over time , of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis . Trial registration number : NCT00988221 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 Introduction While adalimumab is licensed for ankylosing spondylitis ( AS ) , open uncontrolled studies suggest therapeutic efficacy of TNF-inhibitors in juvenile onset AS ( JoAS ) . Methods A total of 32 patients aged 12 to 17 years with severe , active and refractory JoAS were enrolled in a multicenter , r and omized , double-blind , placebo-controlled parallel study of 12 weeks , followed by open-label adalimumab until week 24 for all patients . ASAS40 was used as the primary , and ASAS20 , PedACR and single items were used as the secondary outcome measures for the intention to treat population . Results A total of 17 patients were r and omized to receive adalimumab 40 mg/2 weeks and 15 patients received placebo .  Two patients ( one of each group ) discontinued prematurely due to insufficient efficacy and were labeled as non-responders . In the double-blind part , more patients on adalimumab achieved an ASAS40 at week 4 ( 41 % ) , week 8 ( 53 % ) and week 12 ( 53 % ) than on placebo ( 20 % , 33 % , 33 % ) , while differences at week 8 only reached borderline significance ( P = 0.05 ) . Also , at 4 , 8 and 12 weeks ASAS20/PedACR30/70 response rates were higher in the adalimumab group ( 53%/53%/29 % ; 59%/76%/41 % ; 53%/65%/53 % ) compared to placebo ( 27%/27%/7 % ; 27%/33%/13 % ; 33%/40%/27 % ) . In the adalimumab group a significant decrease of all disease activity parameters was noted at week 12 and was even more pronounced at week 24 . At week 12 the Bath Ankylosing Spondylitis Disease activity spinal inflammation score decreased by 65 % ( P < 0.001 ) , the back pain score decreased by 50 % ( P < 0.005 ) , the Bath AS Functional Index ( BASFI ) score decreased by 47 % ( P < 0.02 ) , while the Childhood Health Assessment Question naire-Disability Index ( CHAQ-DI ) score improved by 65 % ( P < 0.005 ) . ANCOVA analysis demonstrated superiority of adalimumab over placebo for the physician global assessment of disease activity , parents ' global assessment of subject 's overall well-being , active joint count ( all P < 0.05 ) and erythrocyte sedimentation rate ( ESR ) ( P < 0.01).During the 12-week controlled phase , 29 AEs occurred in 10 patients on placebo compared to 27 AEs in 11 patients on adalimumab . Injection site reactions were the most common adverse events . There were 17 various infections occurring in the double-blind phase , 8 on placebo , 9 on adalimumab and a further 19 in the open label period . Conclusions Adalimumab was well tolerated and highly effective in a double-blind r and omized trial in patients with JoAS . Treatment effects rapidly occurred and persisted for at least 24 weeks of treatment . Trial registration EudraCT 2007 - 003358 - 27 Importance One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α ( TNF-α ) inhibitors ; little guidance on choosing the next treatment exists . Objective To compare the efficacy of a non-TNF-targeted biologic ( non-TNF ) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor . Design , Setting , and Participants A total of 300 patients ( conducted between 2009 - 2012 ) with rheumatoid arthritis , with persistent disease activity ( disease activity score in 28 joints-erythrocyte sedimentation rate [ DAS28-ESR ] ≥ 3.2 [ range , 0 - 9.3 ] ) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter , pragmatic , open-label r and omized clinical trial . The final follow-up date was in August 2013 . Interventions Patients were r and omly assigned ( 1:1 ) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment . The choice of the biologic prescribed within each r and omized group was left to the treating clinician . Main Outcomes and Measures The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism ( EULAR ) scale at week 24 . Secondary outcomes included the EULAR response at weeks 12 and 52 ; at weeks 12 , 24 , and 52 ; DAS28ESR , low disease activity ( DAS28 ≤3.2 ) , remission ( DAS28 ≤2.6 ) ; serious adverse events ; and serious infections . Results Of the 300 r and omized patients ( 243 [ 83.2 % ] women ; mean [ SD ] age , 57.1 [ 12.2 ] years ;  baseline DAS28-ESR , 5.1 [ 1.1 ] ) , 269 ( 89.7 % ) completed the study . At week 24 , 101 of 146 patients ( 69 % ) in the non-TNF group and 76 ( 52 % ) in the second anti-TNF group achieved a good or moderate EULAR response ( OR , 2.06 ; 95 % CI , 1.27 - 3.37 ; P = .004 , with imputation of missing data ; absolute difference , 17.2 % ; 95 % CI , 6.2 % to 28.2 % ) . The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group ( mean difference adjusted for baseline differences , -0.43 ; 95 % CI , -0.72 to -0.14 ; P = .004 ) . At weeks 24 and 52 , more patients in the non-TNF group vs the second anti-TNF group showed low disease activity ( 45 % vs 28 % at week 24 ; OR , 2.09 ; 95 % CI , 1.27 to 3.43 ; P = .004 and 41 % vs 23 % at week 52 ; OR , 2.26 ; 95 % CI , 1.33 to 3.86 ; P = .003 ) . Conclusions and Relevance Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response , a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication . Trial Registration clinical trials.gov Identifier : NCT01000441 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 OBJECTIVE To investigate the effects of an 8-week , 24-session weight-bearing physical conditioning program on disease signs and symptoms in children with chronic arthritis . METHODS In a within-subjects , repeated measures design , 25 subjects , ages 8 - 17 years , with chronic polyarticular juvenile rheumatoid arthritis ( JRA ) , were assessed at study entry , after an 8-week control period , and after an 8-week exercise period , for 1 ) disease status , based on joint count ( JC ) and articular severity index ( ASI ) ( sum of scores for joint swelling , pain on motion , tenderness , and limitations of motion ) ; 2 ) worst pain during the past week , using a 10-cm visual analog scale ( VAS ) , and 3 ) aerobic endurance , using the 9-minute run-walk test of the Health Related Physical Fitness Test battery . The 60-minute conditioning program included warm-up ( 10 minutes ) , low-impact aerobics ( 25 minutes ) , strengthening ( 15 minutes ) , and cool-down and flexibility exercises ( 10 minutes ) . Subjects exercised twice a week at their rheumatology center and once a week at home , using a commercial exercise video-tape supplied by the investigator . RESULTS Significant improvement was found in the ASI ( Friedman analysis of variance [ ANOVA ] ) , JC , and 9-minute run-walk test ( repeated measures ANOVA ) from the pre- to post-exercise tests . Mean VAS pain scores decreased 16 % from study entry to the post-exercise test . Statistically significant improvement ( reliable change index > 1.96 ) occurred in 80 % of subjects on the ASI and 72 % on the JC . CONCLUSION Children and adolescents with chronic polyarticular JRA can improve their aerobic endurance through participation in weight-bearing physical conditioning programs without disease exacerbation or increased pain , and may achieve decreased joint signs and symptoms through increased physical activity 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 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 Objective To compare the relative bioavailability , safety and tolerability of oral methotrexate ( MTX ) and subcutaneous ( SC ) MTX administered via an auto-injector ( MTXAI ) in patients with rheumatoid arthritis ( RA ) . Methods In this r and omised , multicenter , open-label , three-way crossover study , patients ≥18 years with adult RA undergoing treatment with MTX for ≥3 months were assigned to receive MTX 10 , 15 , 20 and 25 mg weekly in a r and om sequence of three treatments : oral , SC into the abdomen and SC into the thigh . For 24 h after administration of each treatment , blood sample s were collected for pharmacokinetic analysis and injection sites were assessed . Results Forty-seven patients completed the study . Systemic exposure of oral MTX plateaued at doses ≥15 mg/week . In contrast , SC MTX demonstrated a linear increase in systemic exposure that was greater than oral MTX at each dose . No unexpected AEs were noted for either formulation . Conclusions Unlike oral MTX , the systemic exposure of SC MTX did not plateau over the doses studied , particularly at doses ≥15 mg/week . In this study , higher systemic MTX exposure was not associated with increases in AEs . Patients with an inadequate clinical response to oral MTX may benefit from higher drug exposure by switching to SC MTX . Trial registration number NCT01618968 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 OBJECTIVE To consider the relevance of the duration of a clinical trial in ankylosing spondylitis : long-term ( i.e. 1 yr ) vs short-term ( i.e. 6 weeks ) assessment of a non-steroidal anti-inflammatory drug (NSAID)-placebo controlled study . METHODS The design was a prospect i ve , multicentre , double-blind , placebo-controlled study of 6 weeks duration with a 12 months double-blind extension . Study drugs were placebo ( n = 121 ) or active NSAID ( n = 352 ) . A decrease of at least 50 % in pain and /or global assessment and /or functional impairment during the study defined the response to treatment . The percentage of patients discontinuing the study drug over time ( life table analysis ) permitted the evaluation of both the efficacy and toxicity . RESULTS Among the 473 recruited patients , the percentage of responders was similar at 1 yr and week 6 with a highly statistically significant difference in favour of the active NSAID groups when compared to placebo ( at 1 yr , 17 % in the placebo group vs 37 , 50 and 43 % in the piroxicam 20 mg , meloxicam 15 mg and meloxicam 22.5 mg , respectively , for the patient 's overall assessment ) without any statistically significant difference between the three active groups . However , evaluation of the patients discontinuing the study drug during the 1 yr of the study permitted the detection of a statistically significant difference between the active NSAID groups . A lower percentage of patients taking meloxicam 22.5 mg had to discontinue the study drug when compared to either meloxicam 15 mg or piroxicam 20 mg ( 37 % vs 53 % and 53 % , respectively , P < 0.05 ) . By 52 weeks , drug-related upper gastrointestinal adverse events occurred in 13 , 32 , 20 and 18 % in the placebo , piroxicam 20 mg , meloxicam 15 mg and meloxicam 22.5 mg groups , respectively . Some of the adverse events occurred only after week 6 . CONCLUSION This study suggests that a 1 yr trial might be of optimum value compared to a 6 week assessment in order to define better the efficacy and tolerability of NSAIDs in ankylosing spondylitis OBJECTIVE To evaluate the safety and efficacy of up to 8 years of etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis ( JRA ) . METHODS Patients with JRA who previously participated in a r and omized controlled trial ( RCT ) of etanercept were eligible to receive etanercept in a long-term open-label extension ( OLE ) trial . Safety end points included the incidences of serious adverse events ( SAEs ) , medically important infections ( MIIs ) , and death . Efficacy end points included the American College of Rheumatology ( ACR ) Pediatric 30 ( Pedi 30 ) , Pedi 50 , Pedi 70 , Pedi 90 , and Pedi 100 criteria for improvement . RESULTS Of the 69 patients originally enrolled in the RCT , 58 ( 84 % ) participated in the OLE , for a total of 318 patient-years of etanercept exposure . A total of 42 of the 58 patients ( 72 % ) entered the fourth year of continuous etanercept treatment , and 26 patients ( 45 % ) entered the eighth year . Sixteen patients ( 23 % of those entering the RCT ) reported 39 SAEs . The overall rate of SAEs ( 0.12 per patient-year ) did not increase with long-term exposure to etanercept . The rate of MIIs ( 0.03 per patient-year ) remained low ; 1 new MII was reported in patients with > or = 5 years of etanercept exposure . No cases of tuberculosis , opportunistic infections , malignancies , lymphomas , lupus , demyelinating disorders , or deaths were reported . An ACR Pedi 70 response or higher was achieved by 100 % of patients with 8 years of data ( 11 of 11 ) and by 61 % of patients according to the last observation carried forward data ( 28 of 46 ) . CONCLUSION These data suggest that the acceptable safety profile of etanercept therapy is maintained for up to 8 years in this population of JRA patients . Improvements in the signs and symptoms of JRA were also maintained for up to 8 years 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 Background There is a lack of published evidence on the importance of methotrexate ( MTX ) dose and route of administration on both its efficacy and adverse events in children with Juvenile Idiopathic Arthritis ( JIA ) . We aim ed to document our clinical practice based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX is associated with clinical ly acceptable adverse effects comparable to those reported for oral treatment . Methods Study inclusion criteria were indication of new MTX therapy for active arthritis in confirmed JIA patients younger than 18 years . Eligible patients were evaluated prospect ively every 3 months for 1 year using st and ardized instruments for treatment response ( American College of Rheumatology Pediatric ( ACRPedi ) response , Juvenile Arthritis Disease Activity Score ( JADAS ) 71 , Clinical ly Inactive Disease ( CID ) ) and adverse events ( laboratory monitoring , Methotrexate Intolerance Severity Score ( MISS ) ) . MTX responders had to achieve at least ACRPedi 70 response . MTX intolerance was defined by MISS ≥ 6 . Results In 45/55 patients ( 81.8 % ) MTX was started as subcutaneous injection . The initial median weekly dose was 14.4 mg/m2 in parenteral and 11.7 mg/m2 in oral administration . MTX therapy was effective in the level of ACRpedi70 and CID in 50.9 % and 30.9 % of patients at month 6 and in 70.9 % and 56.4 % after 12 months of the treatment , respectively . MTX intolerance at 6 and 12 months was noted in 25.5 % and 30.6 % , respectively . Management of intolerance included change in the dose and /or route of administration , education and councelling . Adverse events led to MTX withdrawal in 5 patients ( 9 % ) due to toxicity ( n = 3 ) and intolerance ( n = 2 ) . We did not find any significant predictive factors for either  MTX therapeutic response or intolerance . ConclusionS ubcutaneous MTX weekly dose around 15 mg/m2 is associated not only with a high response rate within the first 12 months of treatment , but also with a relatively low rate of significant adverse effects that would lead to the treatment termination . It allows early recognition of MTX non-responders and addition of biologic therapy . Sustainability of therapeutic effect and longer-term evolution of adverse events will be addressed by an ongoing extension of the study BACKGROUND We compared the safety and efficacy of leflunomide with that of methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a multinational , r and omized , controlled trial . METHODS Patients 3 to 17 years of age received leflunomide or methotrexate for 16 weeks in a double-dummy , blinded fashion , followed by a 32-week blinded extension . The rates of American College of Rheumatology Pediatric 30 percent responses ( ACR Pedi 30 ) and the Percent Improvement Index were assessed at baseline and every 4 weeks for 16 weeks and every 8 weeks during the 32-week extension study . RESULTS Of 94 patients r and omized , 86 completed 16 weeks of treatment , 70 of whom entered the extension study . At week 16 , more patients in the methotrexate group than in the leflunomide group had an ACR Pedi 30 response ( 89 percent vs. 68 percent , P=0.02 ) , whereas the values for the Percent Improvement Index did not differ significantly ( -52.87 percent vs. -44.41 percent , P=0.18 ) . In both groups , the improvements achieved at week 16 were maintained at week 48 . The most common adverse events in both groups included gastrointestinal symptoms , headache , and nasopharyngeal symptoms . Aminotransferase elevations were more frequent with methotrexate than with leflunomide during the initial study and the extension study . CONCLUSIONS In patients with polyarticular juvenile rheumatoid arthritis , methotrexate and leflunomide both result ed in high rates of clinical improvement , but the rate was slightly greater for methotrexate . At the doses used in this study , methotrexate was more effective than leflunomide OBJECTIVES Methotrexate ( MTX ) is the cornerstone disease-modifying anti-rheumatic drug ( DMARD ) in juvenile idiopathic arthritis ( JIA ) . In Dutch patients , MTX intolerance occurred frequently and was associated with subcutaneous ( SC ) administration . The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients . METHODS A cross-sectional study of JIA patients on MTX  was performed . Primary outcome was MTX intolerance , which was determined using the vali date d  Methotrexate Intolerance Severity Score ( MISS ) question naire . The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX  SC and MTX administered orally ( PO ) . RESULTS Of 179 JIA patients on MTX  , 73 ( 40.8 % ) were intolerant . The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO ( adjusted odds ratio 3.37 [ 95 % confidence interval 1.19 - 10.0 ] ) . There was strong evidence that the former experienced more behavioural complaints ( 76.1 % vs. 47.4 % , p=0.001 ) and weak evidence that they experienced more abdominal pain after MTX intake ( 43.5 % vs. 27.4 % , p=0.056 ) . CONCLUSIONS The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects . The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO . The frequently held assumption that SC causes fewer side effects than PO seems unwarranted . Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by r and omised trials BACKGROUND The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis .  Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis , but the supporting data are from uncontrolled trials . METHODS Centers in the United States and the Soviet Union participated in this r and omized , controlled , double-blind trial design ed to evaluate the effectiveness and safety of orally administered methotrexate . Patients received one of the following treatments each week for six months : 10 mg of methotrexate per square meter of body-surface area ( low dose ) , 5 mg of methotrexate per square meter ( very low dose ) , or placebo . The use of prednisone ( less than or equal to 10 mg per day ) and two nonsteroidal antiinflammatory drugs was also allowed . RESULTS The 127 children ( mean age , 10.1 years ) had a mean duration of disease of 5.1 years ; 114 qualified for the analysis of efficacy . According to a composite index of several response variables , 63 percent of the children who received low-dose methotrexate  improved , as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group ( P = 0.013 ) . As compared with the placebo group , the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion ( -11.0 vs. -7.1 ) , the pain-severity score ( -19 vs. -11.5 ) , the number of joints with limited motion ( -5.4 vs. -0.7 ) , and the erythrocyte sedimentation rate ( -19.0 vs. -6 mm per hour ) . In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects ; none had severe toxicity . CONCLUSIONS Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis , and at least in the short term this regimen is safe 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 OBJECTIVE To assess the outcome of adult patients with JIA who received etanercept ( ETA ) during childhood . METHODS JuMBO ( Juvenile arthritis MTX/Biologics long-term Observation ) is an ongoing prospect i ve cohort study . It follows adult JIA patients who were formerly included in the national JIA biologic register . In JuMBO , clinical status , therapy and the occurrence of adverse events are documented every 6 months by physicians ; additionally , patient-derived data are included [ e.g. functional capacity and health-related quality of life ( HRQoL ) ] . Here , data from the last available visit of patients were analysed . RESULTS Until December 2010 , 346 patients with a median age of 21 years were included in JuMBO . The majority of them had polyarthritis . Seventy-eight per cent of them were still on DMARDs , 45 % on ETA . The disease was inactive in about one in five patients . A restricted functional capacity was reported by 51 % of participants and fatigue by 76 % . The patients judged their HRQoL to be lower than a reference group from the general population , but only with regard to physical health . HRQoL correlated with the patient 's perceived fatigue . Most frequently observed comorbidities in the young adults with JIA were disease related and included uveitis , IBDs and psoriasis . During the observation period , 2.1 severe infections and 1.5 new-onset autoimmune events per 100 patient-years were reported in patients on ETA , respectively . CONCLUSION The first data from the JuMBO register indicate an improved long-term outcome of patients with severe JIA treated in the biologic era and an acceptable safety profile of ETA 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 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 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 Objective This report aims to determine the safety , pharmacokinetics ( PK ) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis ( polyJIA ) . Methods In this three-part r and omised double-blinded placebo-controlled withdrawal trial , all patients received open-label  golimumab ( 30 mg/m2 of body surface area ; maximum : 50 mg/dose ) every 4 weeks together with weekly methotrexate during Part 1 ( weeks 0–16 ) . Patients with at least 30 % improvement per American College of Rheumatology Criteria for JIA ( JIA ACR30 ) in Part 1 entered the double-blinded Part 2 ( weeks 16–48 ) after 1:1 r and omisation to continue golimumab or start placebo . In Part 3 , golimumab was continued or could be restarted as in Part 1 . The primary outcome was JIA flares in Part 2 ; secondary outcomes included JIA ACR50/70/90 responses , clinical remission , PK and safety . Results Among 173 patients with polyJIA enrolled , 89.0 % ( 154/173 ) had a JIA ACR30 response and 79.2%/65.9%/36.4 % demonstrated JIA ACR50/70/90 responses  in Part 1 . At week 48 , the primary endpoint was not met as treatment groups had comparable JIA flare rates  ( golimumab vs placebo : 32/78=41 % vs 36/76=47 % ; p=0.41 ) , and rates of clinical remission were comparable ( golimumab vs placebo : 10/78=12.8 % vs 9/76=11.8 % ) . Adverse event and serious adverse event rates were similar in the treatment groups during Part 2 . Injection site reactions occurred with < 1 % of all injections . PK analysis confirmed adequate golimumab dosing for polyJIA . Conclusion Although the primary endpoint was not met , golimumab result ed in rapid , clinical ly meaningful , improvement in children with active polyJIA . Golimumab was well tolerated , and no unexpected safety events occurred . Clinical Trial Registration NCT01230827 ; Results 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 : 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 assess the efficacy , tolerability , and safety of sulfasalazine ( SSZ ) in the treatment of juvenile chronic arthritis ( JCA ) . METHODS We conducted a 24-week r and omized , placebo-controlled , double-blind , multicenter study of patients with active JCA of both oligoarticular and polyarticular onset . Patients were treated with a dosage of 50 mg/kg/day of SSZ ( maximum 2,000 mg/day ) or placebo . The efficacy variables were joint scores , physician 's , parents ' , and patient 's overall assessment s , and laboratory parameters of inflammation . RESULTS Of the 69 patients enrolled , 52 ( 75 % ) completed the trial . Six patients ( 18 % ) withdrew from the placebo group , and 11 ( 31 % ) withdrew from the SSZ group ( P = 0.18 ) . In the intention-to-treat analysis of end point efficacy , between-group differences were significant for the overall articular severity score ( P = 0.02 ) , all global assessment s ( P = 0.01 ) , and the laboratory parameters ( P < 0.001 ) . Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal ( P < 0.001 ) , but in all instances , these events were transient or reversible upon cessation of treatment . CONCLUSION The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA , although it was not well tolerated in one-third of the patients OBJECTIVE To examine the efficacy and safety of different rituximab doses plus methotrexate ( MTX ) , with or without glucocorticoids , in patients with active rheumatoid arthritis ( RA ) resistant to disease-modifying antirheumatic drugs ( DMARDs ) , including biologic agents . METHODS A total of 465 patients were r and omized into 9 treatment groups : 3 rituximab groups ( placebo [ n = 149 ] , 500 mg [ n = 124 ] , or 1,000 mg [ n = 192 ] on days 1 and 15 ) each also taking either placebo glucocorticoids , intravenous methylprednisolone premedication , or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks . All patients received MTX ( 10 - 25 mg/week ) ; no other DMARDs were permitted . RESULTS Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20 % improvement criteria ( achieved an ACR20 response ) at week 24 ( 55 % and 54 % , respectively ) compared with placebo ( 28 % ; P < 0.0001 ) . ACR50 responses were achieved by 33 % , 34 % , and 13 % of patients , respectively ( P < 0.001 ) , and ACR70 responses were achieved by 13 % , 20 % , and 5 % of patients ( P < 0.05 ) . Changes in the Disease Activity Score in 28 joints ( -1.79 , -2.05 , -0.67 ; P < 0.0001 ) and moderate to good responses on the European League Against Rheumatism criteria ( P < 0.0001 ) reflected the ACR criteria responses . Glucocorticoids did not contribute significantly to the primary efficacy end point , ACR20 response at 24 weeks . Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events ; oral glucocorticoids conferred no additional safety benefit . Rituximab was well tolerated ; the type and severity of infections was similar to those for placebo . CONCLUSION Both rituximab doses were effective and well tolerated when added to MTX therapy in patients with active RA . The primary end point ( ACR20 response ) was independent of glucocorticoids , although intravenous glucocorticoid premedication improved tolerability during the first rituximab infusion Objectives In juvenile idiopathic arthritis ( JIA ) , the efficacy of very early disease-modifying drug therapy , synthetic or biological , is not well known . Three alternative strategies were compared for treating recent‑onset polyarticular JIA . Methods In a 54-week multicentre open-label clinical trial , 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4–15 years were r and omly assigned into three treatment arms . The efficacy of infliximab plus methotrexate ( TNF ) was compared to that of two synthetic therapies : methotrexate alone ( MTX ) and DMARD methotrexate , sulphasalazine and hydroxychloroquine in combination ( COMBO ) . Primary endpoint was American College of Rheumatology paediatric 75 % improvement ( ACR Pedi 75 ) . Secondary endpoints were inactive disease and safety . Results In 59 patients , mean ( ±SE ) age at baseline was 9.6±0.4 years , duration of JIA 1.9±0.2 months and number of active joints 18±1 . ACR Pedi 75 was achieved in 100 % ( 19/19 ) of patients receiving TNF , 65 % ( 13/20 ) on COMBO ( 95 % CI 44 % to 86 % ) and 50 % ( 10/20 ) on methotrexate ( 95 % CI 28 % to 72 % ) p<0.0001 . Thirteen patients receiving TNF ( 68 % ; 95 % CI 47 % to 89 % ) achieved inactive disease , whereas eight ( 40 % ; 95 % CI 22 % to 63 % ) on COMBO and five ( 25 % ; 95 % CI 6 % to 44 % ) on methotrexate did ( p=0.002 ) . Patients on TNF spent a mean 26 weeks ( 95 % CI 18 to 34 ) with inactive disease , longer than did those receiving COMBO ( 13 weeks ; 95 % CI 6 to 20 ) , or methotrexate ( 6 weeks ; 95 % CI 2 to 10 ) . Serious adverse events were rare . Conclusion In early polyarticular JIA , targeting to achieve minimally active or inactive disease , infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone OBJECTIVE To assess the efficacy , safety , and tolerability of etoricoxib , a cyclooxygenase 2 ( COX-2 ) selective inhibitor , administered continuously over 52 weeks for the treatment of ankylosing spondylitis ( AS ) . METHODS This 2-part , multicenter , double-blind , parallel-group , 52-week study evaluated 2 doses of etoricoxib ( 90 and 120 mg ) compared with naproxen at 1,000 mg . A 6-week , active-comparator- and placebo-controlled period ( part I ) was followed by a 46-week active-comparator-controlled period ( part II ) . The primary outcome measures ( on 100-mm visual analog scales ) were patient 's assessment of spine pain , patient 's global assessment of disease activity , and the Bath Ankylosing Spondylitis Functional Index . RESULTS Of the 387 patients r and omized to receive treatment , 301 ( 77.8 % ) completed part I and 284 ( 75.9 % ) completed part II . Compared with placebo over 6 weeks , those receiving 90 mg etoricoxib , 120 mg etoricoxib , and naproxen demonstrated significantly ( P < 0.001 ) greater improvement in all primary end points ; treatment effects ( expressed as the difference in least squares mean change versus placebo ) were 21 - 29 mm for spine pain , 18 - 25 mm for disease activity , and 11 - 15 mm for function . Compared with patients receiving naproxen , significantly greater improvement in all primary end points was demonstrated in the combined group receiving either 90 mg etoricoxib or 120 mg etoricoxib over 6 weeks , in each individual etoricoxib treatment group over 6 weeks , and in the combined etoricoxib group over 1 year ( all P < 0.05 ) ; results for secondary and exploratory end points were generally consistent with those from the primary analysis . Among all groups , there were no significant differences in the incidence of overall clinical , drug-related , or serious adverse experiences ( AEs ) and discontinuations due to AEs . Safety observations during part II were generally consistent with those in part I. CONCLUSION Etoricoxib at doses of 90 mg and 120 mg demonstrated superior efficacy compared with placebo over 6 weeks , and compared with naproxen over 1 year . These study results demonstrate that etoricoxib is generally safe , well-tolerated , and efficacious for the treatment of AS OBJECTIVE To identify a core set of outcome variables for the assessment of children with juvenile arthritis ( JA ) , to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinical ly important improvement , and to promote this definition as a single efficacy measure in JA clinical trials . METHODS A core set of outcome variables was established using a combination of statistical and consensus formation techniques . Variables in the core set consisted of 1 ) physician global assessment of disease activity ; 2 ) parent/patient assessment of overall well-being ; 3 ) functional ability ; 4 ) number of joints with active arthritis ; 5 ) number of joints with limited range of motion ; and 6 ) erythrocyte sedimentation rate . To establish a definition of improvement using this core set , 21 pediatric rheumatologists from 14 countries met , and , using consensus formation techniques , scored each of 72 patient profiles as improved or not improved . Using the physicians ' consensus as the gold st and ard , the chi-square , sensitivity , and specificity were calculated for each of 240 possible definitions of improvement . Definitions with sensitivity or specificity of < 80 % were eliminated . The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo , using actual trial data , was then observed . Each definition was also ranked for face validity , and the sum of the ranks was then multiplied by the kappa statistic . RESULTS The definition of improvement with the highest final score was as follows : at least 30 % improvement from baseline in 3 of any 6 variables in the core set , with no more than 1 of the remaining variables worsening by > 30 % . The second highest scoring definition was closely related to the first ; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials , except with different variables . This indicates convergent validity of the process used . CONCLUSION We propose a definition of improvement for JA . Use of a uniform definition will help st and ardize the conduct and reporting of clinical trials , and should help practitioners decide if a child with JA has responded adequately to therapy . We are in the process of prospect ively validating this definition and several others that scored highly 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 compare the efficacy and safety of methotrexate ( MTX ) after oral and intramuscular administration in children with juvenile chronic arthritis ( JCA ) . METHODS Pediatric rheumatology centers in Italy participated in this short-term , prospect i ve , open trial . Each investigator was allowed to choose the oral or intramuscular route of administration according to his personal preference in everyday clinical practice . Patients enrolled by each center were given MTX through the same method of administration . All patients received 10 mg/m2 of MTX each week for six months . RESULTS A total of 257 patients with JCA ( 127 treated orally and 130 intramuscularly ) were enrolled in the trial by 11 Italian centers . The response rate after 6 months of MTX therapy was 58 % in the oral and 61 % in the intramuscular cohort . The frequency of adverse side effects did not differ significantly between the two treatment groups . CONCLUSION The results of this study suggest that MTX at the conventional dose regimen is equally effective and has a similar safety profile in children with JCA when administered orally or by intramuscular injections OBJECTIVE To evaluate the short-term efficacy of celecoxib , a cyclooxygenase 2-specific inhibitor , in the treatment of ankylosing spondylitis ( AS ) . METHODS The study was a 6-week r and omized , double-blind , placebo-controlled trial with 3 treatment arms : placebo , ketoprofen 100 mg twice daily , and celecoxib 100 mg twice daily . Patients who had AS according to the modified New York criteria , without peripheral synovitis and with active disease ( pain > or = 40 mm on a 100-mm visual analog scale [ VAS ] and an increase in pain of at least 30 % after nonsteroidal antiinflammatory drug withdrawal ) were eligible for study . Primary outcome measures were change in pain intensity ( VAS ) and change in functional impairment ( Bath Ankylosing Spondylitis Functional Index [ BASFI ] ) . RESULTS Of the 246 r and omized patients , 76 were allocated to receive placebo , 90 ketoprofen , and 80 celecoxib . There were no statistically significant differences between treatment groups at study entry . During the 6 weeks of the study , the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group , with a trend in favor of celecoxib when the 2 active treatments were compared . The mean changes were -13 mm , -21 mm , and -27 mm ( P = 0.006 ) for pain and 1 , -6 , and -12 ( P = 0.0008 ) for BASFI score in the placebo , ketoprofen , and celecoxib groups , respectively . During treatment , the number of patients reporting epigastric pain was 6 ( 8 % ) , 13 ( 14 % ) , and 10 ( 13 % ) in the placebo , ketoprofen , and celecoxib groups , respectively . CONCLUSION The results of this study confirm the clinical ly relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage , with significant improvement of both pain and function in patients with AS OBJECTIVE To analyze patterns of stress , mood , disease symptoms , and activity reduction in children with polyarticular arthritis , using a prospect i ve daily diary method . METHODS For a 2-month period , 51 children with polyarticular arthritis ( mean age 12.4 years , 65 % female ) completed daily diaries that included measures of symptoms of pain , stiffness , and fatigue , as well as stress , mood , and activity reduction . Functional status and disease activity were assessed at the initial and followup evaluations with use of the Childhood Health Assessment Question naire , physician global assessment , joint count , and laboratory testing . RESULTS Children reported having pain , stiffness , and fatigue on > 70 % of days , with significant variability in symptom levels . Results revealed significant same-day relationships between stress , mood , and disease symptoms , after controlling for covariates . Specifically , daily fluctuations in both stress and mood were predictive of increased pain , stiffness , and fatigue . Increases in daily stress , mood , and disease symptoms were also significantly related to decreased participation in social activities on a day-to-day basis . Only mood and stiffness were predictors of a cutback in school attendance . CONCLUSION Stress and mood are important predictors of daily disease symptoms in children with polyarticular arthritis . Moreover , daily fluctuations in stress , mood , and disease symptoms are predictive of aspects of daily function , including participation in school and social activities . Thus , health care providers should solicit daily symptom reports when making decisions regarding clinical management . Nonpharmacologic interventions such as cognitive-behavioral therapy and stress management may be useful adjuvant therapy when treating the disease symptoms of children with polyarticular arthritis Importance Published evidence on the long-term safety of etanercept ( ETA ) and adalimumab ( ADA ) in patients with polyarticular juvenile idiopathic arthritis ( pJIA ) is still limited . Objectives To investigate the rates of serious adverse events ( SAE ) and of events of special interest ( ESI ) under ETA and ADA treatment . Design , setting and participants Patients with pJIA were prospect ively observed in the national JIA biological register , Biologika in der Kinderrheumatologie , and its follow-up register , Juvenile arthritis Methotrexate/Biologics long-term Observation . Main outcomes and measures We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate ( MTX ) . Results Among the 1414 patients treated with ETA ( n=1414 ; 4461 exposure years ( EY ) ) and ADA ( n=320 ; 493 EY ) , significantly more SAE , infections and medically important infections were observed ( ETA : 4.5 , 5.7 , 0.9 ; ADA : 4.7 , 11.4 , 0.4 per 100 EY ) compared with those treated with MTX alone ( n=1455 ; 2.907 EY ; 2.6 , 5.5 , 0.5 per 100 EY ) . The risk for malignancies was not significantly increased for ETA and ADA compared with MTX ( 0.09 , 0.27 and 0.07/100 person-years ) . Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease ( IBD ) and incident uveitis ( 0.5 and 0.8/100 EY ) than patients treated by ETA in combination with MTX ( 0.1 and 0.2/100 EY ) or MTX alone ( 0.03 and 0.1/100 EY ) . Conclusions and relevance Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA . However , whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort OBJECTIVE To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis ( JRA ) . METHODS This was an international , multicenter , r and omized , placebo-controlled , double-blind study . One hundred twenty-two children with persistent polyarticular JRA despite prior methotrexate ( MTX ) therapy were r and omized to receive infliximab or placebo for 14 weeks , after which all children received infliximab through week 44 . Patients received MTX plus infliximab 3 mg/kg through week 44 , or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44 . RESULTS Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology ( ACR ) Pediatric 30 ( Pedi 30 ) criteria for improvement at week 14 ( 63.8 % and 49.2 % , respectively ) , the between-group difference in this primary efficacy end point was not statistically significant ( P = 0.12 ) . By week 16 , after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab , an ACR Pedi 30 response was achieved in 73.2 % of all patients . By week 52 , ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6 % and 51.8 % , respectively , of patients . Infliximab was generally well tolerated , but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg , with more frequent occurrences of serious adverse events , infusion reactions , antibodies to infliximab , and newly induced antinuclear antibodies and antibodies to double-str and ed DNA observed with the 3 mg/kg dose . CONCLUSION While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year , achievement of the primary efficacy end point at 3 months did not differ significantly between  infliximab-treated  and  placebo-treated  patients . Safety data indicated that the 6-mg/kg dose may provide a more favorable risk/benefit profile . These results warrant further investigation in children with JRA OBJECTIVE To evaluate the long-term efficacy and safety of etanercept in children with juvenile rheumatoid arthritis ( JRA ) participating in an ongoing multicenter , open-label , extended-treatment trial . All patients had been participants in an initial r and omized efficacy and safety trial of etanercept . METHODS Etanercept was administered at a dosage of 0.4 mg/kg ( maximum 25 mg ) subcutaneously twice each week . Safety and efficacy evaluations were performed every 3 - 4 months . The JRA 30 % definition of improvement ( DOI ) was defined as improvement of > or = 30 % in at least 3 of 6 response variables used to assess disease activity , with no more than 1 variable worsening by more than 30 % . RESULTS At the time of analysis , 48 of the 58 patients ( 83 % ) were still enrolled in the study ; 43 of them ( 74 % ) had completed 2 years of treatment . Of these 43 patients , 81 % met the JRA 30 % DOI , 79 % met the JRA 50 % DOI , and 67 % met the JRA 70 % DOI . Ten children started low-dose methotrexate after year 1 . Of the 32 children taking prednisone , the dosage was decreased to < 5 mg/day in 26 ( 81 % ) . Two children had serious infections ( varicella with aseptic meningitis in one and complicated sepsis in the other ) . In general , adverse events were of the types seen in a general pediatric patient population . CONCLUSION Children with severe , longst and ing , methotrexate-resistant polyarticular JRA demonstrated sustained clinical improvement with > 2 years of continuous etanercept treatment . Etanercept was generally well-tolerated . There were no increases in the rates of adverse events over time . However , children taking etanercept should be monitored closely for infections OBJECTIVE To evaluate the efficacy and safety of methotrexate ( MTX ) compared with placebo in patients with active ankylosing spondylitis ( AS ) . METHODS This 24 week , double bind , r and omized , placebo controlled trial compared the response between MTX 7.5 mg/week or placebo in patients with active AS . The primary outcome measure was a composite index of improvement in 5 of the following scales : severity of morning stiffness , physical well being , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Health Assessment Question naire for Spondyloarthropathies ( HAQ-S ) , and physician and patient global assessment of disease activity . RESULTS Seventeen patients received MTX and 18 placebo .  In the intention-to-treat analysis at 24 weeks , 53 % of patients in the MTX group had a treatment response , compared with 17 % in the placebo group ( p = 0.03 ) . We observed significant improvements with MTX in physical well being ( p = 0.009 ) , BASDAI ( p = 0.02 ) , BASFI ( p = 0.02 ) , physician global assessment ( p < 0.001 ) , patient global assessment ( p = 0.03 ) , and HAQ-S ( p = 0.02 ) . In the adjusted analysis only MTX determined the improvement in the primary outcome . At the end of the trial , one patient with MTX  withdrew due to a lack of compliance , and one with placebo due to a lack of efficacy . We did not observe significant differences in rates of side effects between the 2 groups . CONCLUSION MTX is safe and effective for patients with AS . Longterm studies are needed to evaluate the permanence of its benefit OBJECTIVE To analyze patterns of daily pain , stiffness , and fatigue related to juvenile arthritis ; to examine the relationships of demographics , disease severity , and psychological adjustment to daily disease symptoms ; and to examine daily disease symptoms as predictors of reduced participation in school and social activity . METHODS For a 2-month period , 41 children with polyarticular juvenile arthritis completed daily diaries that included measures of symptoms and function . Children also underwent an initial evaluation and 4 followup evaluations that included a joint count , laboratory testing , and completion of question naires assessing physical and psychosocial functioning . RESULTS Children reported having pain an average of 73 % of days , with the majority of children ( 76 % ) reporting pain on > 60 % of all days . On average , children described the intensity of their daily pain as being in the mild to moderate range ; however , a significant subgroup ( 31 % ) reported pain in the severe range . Higher physician global assessment ratings , increased functional disability , and increased anxiety were significantly associated with increased daily pain and other daily symptoms . Multilevel r and om-effects analyses indicated that increased daily symptoms of pain , stiffness , and fatigue were significant predictors of reduced participation in school and social activities . CONCLUSION Physicians should consider treating pain more aggressively in children with arthritis , in order to preserve function in school and social domains , as well as physical function . Moreover , optimal pain management in children with arthritis should include therapeutic regimens addressing anxiety as well as st and ard pharmacologic interventions Since the introduction of intra-articular steroid therapy 40 yr ago there have been many changes in the treatment of rheumatoid patients . Previous studies suggest differing times of response for the same agents . This study reports the response , measured by a five-point pain chart , of 300 patients with painful rheumatoid knees . Sixty received hydrocortisone succinate ( HC ) , 150 received triamcinolone acetonide ( TA ) , and 120 triamcinolone hexacetonide ( TH ) . Results demonstrated little effect with HC , but good responses with TA and TH . More patients were rendered painfree for a longer time with TH ; 18 % at 12 weeks , as against 9 % with TA ( chi 2 test P < 0.005 ) . At 12 weeks 59 % showed continued improvement with TH as against 44 % with TA ( chi 2 test P < 0.05 ) . TH is the preferred preparation for injection of the rheumatoid knee Objective To investigate the effects of electromyographic ( EMG ) biofeedback training on pain , quadriceps strength , and functional ability in juvenile rheumatoid arthritis ( JRA ) . Design This is a r and omized controlled study ; 36 children ( 11 boys and 25 girls ) with polyarticular JRA , with ages ranging from 8 to 13 years , were selected and assigned r and omly , using computer-generated r and om numbers , into 2 groups . The control group ( n = 18 ) received the conventional physical therapy program , whereas the study group ( n = 18 ) received the same program as the control group in addition to EMG biofeedback-guided isometric exercises for 3 days a week for 12 weeks . Pain , peak torque of quadriceps strength , and functional ability were evaluated before , after 6 weeks , and at the end of 12 weeks of the treatment program . Results By 6 weeks , significant differences were observed in the study group ( P < 0.05 ) in all measured variables except pain levels , whereas nonsignificant differences were observed in all measured variables in the control group . By 12 weeks , each group demonstrated significant improvements in pain , quadriceps strength , and functional ability ( P < 0.05 ) , with significantly greater improvements seen in the study group compared to the control group ( P < 0.05 ) . Both groups showed significant improvement at 12 weeks compared to that at 6 weeks . Conclusions Electromyographic biofeedback may be a useful intervention modality to reduce pain , improve quadriceps strength , and functional performance in JRA Objective : To examine the potential therapeutic effect of methotrexate 20 mg given weekly as subcutaneous injections to 20 patients with ankylosing spondylitis refractory to non-steriodal antirheumatic drugs . Patients and methods : 20 patients with ankylosing spondylitis , a mean Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score of 5.6 ( range 4–9.3 ) and predominantly axial manifestations were treated with weekly 15 mg methotrexate subcutaneously for 4 weeks , which was then increased to 20 mg subcutaneously for the next 12 weeks . Clinical outcome assessment s included , among others , BASDAI score physical function , spinal mobility , patients ’ and physicians ’ global assessment ( visual analogue scale ) , peripheral joint assessment , quality of life ( Short Form 36 ) and C reactive protein . The primary end point of the study was a 20 % improvement on the ASsessment s in Ankylosing Spondylitis ( ASAS 20 ) scale . Results : Using an intention-to-treat analysis , ASAS 20 was achieved in only 25 % of patients . An ASAS 40 response was achieved in 10 % of patients , and no patient reached an ASAS 70 response or the ASAS criteria for partial remission . For the mean BASDAI score , no change was observed between baseline and week 16 ( baseline 5.6 v week 16 , 5.6 ) . No improvement was observed in any of the clinical parameters or C reactive protein , except a small but non-significant decrease in the number of swollen joints . Conclusions : In this open study , methotrexate did not show any benefit for axial manifestations in patients with active ankylosing spondylitis beyond the expected placebo response 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 We report long-term safety & efficacy of infliximab (IFX)+ methotrexate ( MTX ) treatment in JRA patients . In an international , multicenter , r and omized , double-blind study , 122 children w/active polyarticular JRA despite prior MTX therapy  received MTX plus a 3-dose induction ( wks 0 , 2 , 6 ) of IFX 3 mg/kg through wk 44 , or placebo ( PBO ) for 14 wks followed by IFX 6 mg/kg ( wks 14 , 16 , 20 , & then q8 wks ) through wk 44 . Patients completing treatment through wk 44 were eligible to enter an open-label extension ( OLE ) of IFX 3 mg/kg , beginning at wk 52 & continuing q8 wks through wk 196 . All patients continued with concomitant MTX . Physicians could increase or decrease the IFX dose by ≤1.5 mg/kg/infusion q8 wks , up to 6 mg/kg or down to 3 mg/kg , based on clinical response . Primary endpoint was the proportion of patients meeting ACR-Pedi-30 , defined as improvement of ≥30 % in ≥3 of 6 core variables , & ≤1 of the remaining variables worsened by > 30 % . Remission was defined as 0 joints with active arthritis , normal ESR , & physician 's global assessment ≤10 mm on a 10-cm visual analog scale . 78/122(63.9 % ) children entered the OLE . The mean(SD ) IFX  dose at wk 196 was 4.4(1.6)mg/kg . IFX  was well-tolerated;14.1 % of patients discontinued due to adverse events ( AE ) from wks 52–204 . The distribution/types of AE were similar to those in the first 52 wks & no new safety issues were reported . Among the 36 study patients by wk 204 , ACR-Pedi-30/50/70/90 responses were 91.7%(33/36 ) , 83.3%(30/36 ) , 69.4%(25/36 ) , & 50%(18/36 ) , respectively . 39%(14/36 ) of patients achieved remission . From wk 52 through wk 216 , 36.6%(26/71 ) of patients were positive for IFXantibodies ; 57.7%(15/26 ) of these had an infusion reaction . Continuous IFX+MTX administered up to 4 yrs was safe & effective in JRA patients , although accompanied by a high rate of patient discontinuation , which included subjects in remission OBJECTIVE To evaluate the clinical relevance of CRP in AS and investigate the treatment effect of NSAIDs/coxibs on CRP . METHODS Data of 851 patients with painful axial AS participating in two r and omized controlled trials evaluating coxibs ( celecoxib ) and NSAIDs ( naproxen/ketoprofen )  were used . The clinical relevance of CRP in AS was studied : the number of patients with abnormal CRP at baseline was expressed as a percentage , and the correlation among CRP , patient ( age and gender ) and disease [ Bath AS Disease Activity Index ( BASDAI ) , Bath AS Functional Index ( BASFI ) ] characteristics was investigated . The st and ardized response mean ( SRM ) over placebo was used to detect the treatment effect of NSAIDs/coxibs on CRP . RESULTS The 851 enrolled patients ( 73 % of whom were men ) had an active disease , as assessed through functional impairment .  Mean ( s.d . ) baseline CRP was 14 ( 19 ) ( median 7.2 ) mg/l ; 61 % of patients had an increased CRP . The CRP levels were correlated positively with male sex , BASDAI and BASFI and negatively with age ( multivariate analysis ) . There was a significant difference in the changes of CRP between placebo and NSAIDs/coxibs group ( P = 0.003 ; SRM over placebo : 0.25 ) . Such a treatment effect was of higher magnitude in the subgroup of patients with increased CRP and usually of lower magnitude than the treatment effect of other outcome variables such as BASDAI and BASFI . CONCLUSIONS Increased CRP was frequently observed in patients with painful axial AS and was correlated both with activity and functional severity of the disease . The treatment effect of NSAIDs/coxibs was relevant in the subgroup of patients with increased CRP at baseline OBJECTIVE To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis ( JIA ) can induce clinical inactive disease within 6 months . METHODS Between May 2007 and October 2010 , a multicenter , prospect i ve , r and omized , double-blind , placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2 - 16 years with polyarticular JIA of < 12 months ' duration . Patients received either methotrexate ( MTX ) 0.5 mg/kg/week ( maximum 40 mg ) subcutaneously , etanercept 0.8 mg/kg/week ( maximum 50 mg ) , and prednisolone 0.5 mg/kg/day ( maximum 60 mg ) tapered to 0 by 17 weeks ( arm 1 ) , or MTX ( same dosage as arm 1 ) , etanercept placebo , and prednisolone placebo ( arm 2 ) . The primary outcome measure was clinical inactive disease at 6 months . An exploratory phase determined the rate of clinical remission on medication ( 6 months of continuous clinical inactive disease ) at 12 months . RESULTS By 6 months , clinical inactive disease had been achieved in 17 ( 40 % ) of 42 patients in arm 1 and 10 ( 23 % ) of 43 patients in arm 2 ( χ(2 ) = 2.91 , P = 0.088 ) . After 12 months , clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 ( P = 0.053 ) . There were no significant interarm differences in adverse events . CONCLUSION Although this study did not meet its primary end point , early aggressive therapy in this cohort of children with recent-onset polyarticular JIA result ed in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms
target: Good disease control , with therapeutic escalation to achieve low disease activity , was recommended .
background: OBJECTIVE To develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non-systemic polyarthritis , sacroiliitis , or enthesitis .