Etanercept for patients with juvenile idiopathic arthritis: drug levels and influence of concomitant methotrexate: observational study.

BACKGROUND: Etanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN. METHODS: In this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum. RESULTS: Ninety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33-0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups - in MTX group [r = 0.35 (95% CI: 0.14-0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39-0.67)]. CONCLUSION: In the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.

Pain-coping scale for children and their parents: a cross-sectional study in children with musculoskeletal pain.

BACKGROUND: In a chronic pain-causing disease such as juvenile idiopathic arthritis, the quality of coping with pain is crucial. Parents have a substantial influence on their children's pain-coping strategies. This study aimed to develop scales for assessing parents' strategies for coping with their children's pain and a shorter improved scale for children usable in clinical practice. METHODS: The number of items in the Finnish version of the pain-coping questionnaire for children was reduced from 39 to 20. A corresponding reduced scale was created for parental use. We recruited consecutive patients from nine hospitals evenly distributed throughout Finland, aged 8-16 years who visited a paediatric rheumatology outpatient clinic and reported musculoskeletal pain during the past week. The patients and parents rated the child's pain on a visual analogue scale from 0 to 100 and completed pain-coping questionnaires and depression inventories. The selection process of pain questionnaire items was performed using factor analyses. RESULTS: The average (standard deviation) age of the 130 patients was 13.0 (2.3) years; 91 (70%) were girls. Four factors were retained in the new, improved Pain-Coping Scales for children and parents. Both scales had 15 items with 2-5 items/factor. The goodness-of-fit statistics and Cronbach's alpha reliability coefficients were satisfactory to good in both scaled. The criterion validity was acceptable as the demographic, disease related, and the depression and stress questionnaires correlated with the subscales. CONCLUSIONS: We created a shorter, feasible pain-coping scale for children and a novel scale for caregivers. In clinical work, the pain coping scales may serve as a visualisation of different types of coping strategies for paediatric patients with pain and their parents and facilitate the identification of families in need of psychological support.

The Finnish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Finnish language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 173 JIA patients (1.2% systemic, 46.2% oligoarticular, 39.9% RF-negative polyarthritis, 12.7% other categories) and 100 healthy children, were enrolled in five paediatric rheumatology centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Finnish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

[Still's disease--juvenile arthritis with systemic onset]. / Stillin tauti--yleisoireinen lastenreuma.

Systemic onset juvenile idiopathic arthritis is a rare form of juvenile arthritis in which, contrary to autoimmune diseases in general, no association with a certain tissue type has been detected. Together with this fact, the lack of autoantibodies and the general symptoms belonging to the diagnostic criteria of the illness such as high fever, rather speak for its classification into autoinflammatory diseases. Treatment is usually started with anti-inflammatory drugs, often requiring combination with a systemic glucocorticoid. Recognition of interleukins 1 and 6 as central mediators in the pathogenesis of the disease has brought new possibilities for its treatment.

Disease activity of idiopathic juvenile arthritis continues through adolescence despite the use of biologic therapies.

OBJECTIVES: To investigate the use of DMARDs and biologic treatments and disease activity in patients with JIA referred to the adult rheumatology clinic and to provide further information regarding the need for long-term rheumatologic care. METHODS: We studied the data of 154 patients retrospectively from hospital records if they met the following criteria: diagnosis of JIA and at least one visit to the adult rheumatologic unit. Previous and current antirheumatic treatment, duration of biologic therapy and disease activity were recorded. RESULTS: At the end of patient follow-up, the median age of the eligible patients was 19 years (range 16-24 years) and the disease duration was 8 years (range 0-20 years). Twenty-nine per cent of the patients were still on biologic therapies. The total median duration of treatment with at least one biologic agent was 4.2 years, and 44% of treatment durations lasted >5 years. Some disease activity was present in the last year in 58% of patients. Activity in the temporomandibular joint was detected in 14% and uveitis in 8%. Thirteen per cent did not need further specialist care and in 14% all antirheumatic medication could be tapered off. CONCLUSION: Almost one-third of adolescents and young adults with JIA who needed specialist care were on biologics. The need for treatment in many cases is long term (>5 years). Most patients (58%) still showed evidence of mild disease activity. Adolescents and young adults with JIA are a distinct patient group in adult health care and a specialized multidisciplinary approach to treatment is needed.

[Medical treatment of juvenile idiopathic arthritis]. / Lastenreuman hoito kehittyy.

Although etiology of juvenile idiopathic arthritis (JIA) is currently not known, better understanding of immunologic pathways of inflammation and the development of new therapies with biologic agents have remarkably improved the treatment of JIA. However, approximately 30% of the patients with JIA do not seem to response adequately to conventional anti-rheumatic drugs but the arthritis runs a continuously active course and may lead to the evolution of erosions. Such patients benefit from biologic agents, of which the longest clinical experience comes from anti-TNF therapies. Molecules targeting IL-1, IL-6 and B- and T-lymphocytes are also used in the treatment of severe JIA.

Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial.

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 randomly 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.