Gerd Ganser

The provisional Paediatric Rheumatology International Trials Organisation/American College of Rheumatology/european League Against Rheumatism Disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: A prospective validation study†‡

OBJECTIVE To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM). METHODS In 2001, a preliminary consensus-derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence-based, large-scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordance in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physicians global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parents global assessment of patients well-being, 5) functional ability, and 6) health-related quality of life. CONCLUSION The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European League Against Rheumatism, propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

Is tocilizumab an effective option for treatment of refractory uveitis associated with juvenile idiopathic arthritis

To the Editor: Anti-interleukin 6 receptor (anti-IL-6R) antibodies have been effective in experimental models of autoimmune arthritis, encephalomyelitis, and also uveitis1,2. Tocilizumab (TCZ; RoActemra®, Hoffmann-La Roche, Basel, Switzerland), a fully humanized anti-IL-6R antibody, has been approved for the treatment of rheumatoid arthritis. Efficacy has also been shown for systemic-onset juvenile idiopathic arthritis (JIA)3 and vasculitis4. To date, however, no reports have appeared concerning its efficacy in JIA-associated uveitis. In about one-third of JIA patients with uveitis, eye inflammation runs a severe course and vision-threatening complications develop, and immunosuppressive treatment is required5. Because some patients do not respond properly to the widely used disease-modifying antirheumatic drugs (DMARD), including tumor necrosis factor-α (TNF-α) inhibitors, there is a significant need … Address correspondence to Dr. A. Heiligenhaus, Department of Ophthalmology and Ophtha Lab, St. Franziskus Hospital, Hohenzollernring 74, 48145 Munster, Germany. E-mail: arnd.heiligenhaus{at}uveitis-zentrum.de

Long-term outcome of patients with JIA treated with etanercept, results of the biologic register JuMBO

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 prospective 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 patients 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.

Evidence and consensus based GKJR guidelines for the treatment of juvenile idiopathic arthritis

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

The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis

Objectives To develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM). Methods The Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated prospectively up to 24 months. Thirty-eight patients off therapy at 24 months were defined as clinically inactive and included in the reference group. These were compared with a random sample of 76 patients who had active disease at study baseline. Individual measures of muscle strength/endurance, muscle enzymes, physicians and parents global disease activity/damage evaluations, inactive disease criteria derived from the literature and other ad hoc criteria were evaluated for sensitivity, specificity and Cohens κ agreement. Results The individual measures that best characterised inactive disease (sensitivity and specificity >0.8 and Cohens κ >0.8) were manual muscle testing (MMT) ≥78, physician global assessment of muscle activity=0, physician global assessment of overall disease activity (PhyGloVAS) ≤0.2, Childhood Myositis Assessment Scale (CMAS) ≥48, Disease Activity Score ≤3 and Myositis Disease Activity Assessment Visual Analogue Scale ≤0.2. The best combination of variables to classify a patient as being in a state of inactive disease on or off therapy is at least three of four of the following criteria: creatine kinase ≤150, CMAS ≥48, MMT ≥78 and PhyGloVAS ≤0.2. After 24 months, 30/31 patients (96.8%) were inactive off therapy and 69/145 (47.6%) were inactive on therapy. Conclusion PRINTO established data-driven criteria with clearly evidence-based cut-off values to identify JDM patients with clinically inactive disease. These criteria can be used in clinical trials, in research and in clinical practice.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis

AimsJuvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children.MethodsMulticentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs.ResultsInactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by ⩾50% (n=19) or topical steroids reduced to ⩽2 drops/eye/day (n=40) in selected patients. Pre-existing cystoid macular oedema did not resolve under CsA treatment in any of the patients. In nine patients (11%), CsA was discontinued because of systemic hypertension (n=1), elevated creatinine levels (n=3), or other adverse effects (n=5).ConclusionsThese observations suggest that CsA has limited value as a second-line immunosuppressive drug for the treatment of JIA-associated CAU. The efficacy was better as the combination therapy in patients not responding to other immunosuppressives (eg, MTX) than the systemic monotherapy.

Efficacy and safety of oral and parenteral methotrexate therapy in children with juvenile idiopathic arthritis: an observational study with patients from the German Methotrexate Registry.

The German Methotrexate Registry has been collecting data concerning the efficacy and safety of methotrexate (MTX) treatment since 2005. The aim of this retrospective analysis is to compare oral and parenteral MTX treatment regarding efficacy and safety.

Arthrosonography of hip and knee joints in the follow up of juvenile rheumatoid arthritis

Objective: To evaluate sensitivity of arthrosonography of hip and knee joints for monitoring disease activity in juvenile rheumatoid arthritis (JRA). Methods: Twenty eight patients with JRA with active disease at entry in 15 hips and 38 knee joints were followed up three times in intervals of 4–6 weeks. Sonographic, clinical, and laboratory findings were documented at the same time in clinically active and inactive disease. As controls of the sonographic variables 10 children without a history of arthritis were examined by ultrasound. Results: In active arthritis of the hip joint 19/31 (61%) examinations showed a pathological widening of the synovial joint space. There was no significant correlation between sonographic and clinical measures of disease activity in coxitis. Marked effusion within the suprapatellar pouch was seen in 87% and thickening of the synovial membrane in 92% of cases of active gonarthritis in patients with JRA. There was a significant difference in the number of patients with joint effusion and in the mean joint effusion between patients with clinically active gonarthritis at entry and inactive arthritis at follow up (p<0.001). In contrast, synovial thickening persisted in about 80% after induction of clinical remission. Conclusion: The data confirm the high sensitivity of arthrosonography in imaging changes in hip and knee joints of patients with JRA. Sonographic effusion of the knee provided the highest correlation with measures of clinical disease activity. Further prospective studies should evaluate whether persistent thickening of the synovial membrane detected by ultrasound in clinically inactive arthritis indicates residual inflammatory activity and an increased risk of relapse.

Efficacy and Safety of Adalimumab as the First and Second Biologic Agent in Juvenile Idiopathic Arthritis: The German Biologics JIA Registry

To evaluate the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA).