Heinrike Schmeling

The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort

Objective To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. Methods Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. Results In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. Conclusions Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.

Consensus treatments for moderate juvenile dermatomyositis: Beyond the first two months. Results of the Second Childhood Arthritis and Rheumatology Research Alliance Consensus Conference

To use consensus methods and the considerable expertise contained within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) organization to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (DM) to span the full course of treatment.

Clinical Characteristics of Children With Juvenile Dermatomyositis: The Childhood Arthritis and Rheumatology Research Alliance Registry

To investigate aspects of juvenile dermatomyositis (DM), including disease characteristics and treatment, through a national multicenter registry.

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).

Nailfold capillary density is importantly associated over time with muscle and skin disease activity in juvenile dermatomyositis

OBJECTIVES To investigate the longitudinal association of nailfold capillary density (NCD; as a potential marker of activity) with various other clinical measures of disease activity and to evaluate baseline NCD as a predictor of disease outcome in children with JDM. METHODS Data from 809 clinic visits from 92 JDM patients were prospectively collected at each clinic visit over a time period of 5.5 years. The number of capillaries per millimetre at the distal nailfold was scored using a stereomicroscope. Disease activity was determined using the Childhood Myositis Assessment Scale (CMAS) and a modification of the validated disease activity score (DAS), which included three skin (SDAS) and three muscle (MDAS) criteria. An inception cohort subgroup (n=28) with a baseline visit at diagnosis was analysed separately. RESULTS Both DAS subscores, MDAS (β = -0.04437, P < 0.0001) and SDAS (β = -0.1589, P < 0.0001), as well as the CMAS (β = 0.02165, P < 0.0001) were significantly associated with loss of end row nailfold capillary over time (multiple regression mixed-model analysis). All patients in the inception subcohort showed a reduced baseline NCD (diagnostic sensitivity = 100%) that improved as the disease improved, but this did not predict longer term outcome or course of disease. CONCLUSION NCD is a marker of skin and muscle disease activity, and is an important measure of disease activity changes from visit to visit. Determination of capillary density may be useful when making treatment decisions. A decrease in NCD may be considered for inclusion in the diagnostic criteria due to its high sensitivity.

Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study

In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria.

Development of System-level Performance Measures for Evaluation of Models of Care for Inflammatory Arthritis in Canada

Objective. To develop system-level performance measures for evaluating the care of patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis. Methods. This study involved several methodological phases. Over multiple rounds, various participants were asked to help define a set of candidate measurement themes. A systematic search was conducted of existing guidelines and measures. A set of 6 performance measures was defined and presented to 50 people, including patients with IA, rheumatologists, allied health professionals, and researchers using a 3-round, online, modified Delphi process. Participants rated the validity, feasibility, relevance, and likelihood of use of the measures. Measures with median ratings ≥ 7 for validity and relevance were included in the final set. Results. Six performance measures were developed evaluating the following aspects of care, with each measure being applied separately for each type of IA except where specified: waiting times for rheumatology consultation for patients with new onset IA, percentage of patients with IA seen by a rheumatologist, percentage of patients with IA seen in yearly followup by a rheumatologist, percentage of patients with RA treated with a disease-modifying antirheumatic drug (DMARD), time to DMARD therapy in RA, and number of rheumatologists per capita. Conclusion. The first set of system-level performance measures for IA care in Canada has been developed with broad input. The measures focus on timely access to care and initiation of appropriate treatment for patients with IA, and are likely to be of interest to other arthritis care systems internationally.

Inflammatory biomarkers of pediatric focal cerebral arteriopathy

Focal cerebral arteriopathy (FCA), defined as unifocal or multifocal stenosis of the large or medium-sized blood vessels, is a leading etiology of childhood arterial ischemic stroke (AIS).[1][1] Pathophysiology is poorly understood but inflammatory mechanisms are suspected.[2][2] Recurrence is high

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort

Objective To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare. Methods We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan–Meier methods, and associated features were identified using Cox regression. Results 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. Conclusions In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.

Autoantibodies to Dense Fine Speckles in Pediatric Diseases and Controls

Objective. Autoantibodies to the dense fine speckled 70 kDa antigen (DFS70) are reported to be more common in individuals who do not have an antinuclear antibody (ANA)-associated rheumatic disease (AARD) than in patients with AARD. The frequency of anti-DFS70 antibodies has been thoroughly studied in adult but not in pediatric populations. The primary objective of this observational study was to determine the frequency of anti-DFS70 in pediatric AARD and reference cohorts. Methods. Sera from 743 children with AARD and related conditions, and 345 samples from reference cohorts (healthy children and those being investigated for AARD) were studied for anti-DFS70 autoantibodies as measured by a chemiluminescence immunoassay. A de-identified administrative database was used to retrieve demographic, serologic, and clinical data. Results. Anti-DFS70 antibodies were seen in 2.1% of healthy children and in 4.5% of sera from pediatric individuals referred for ANA testing. The frequency of anti-DFS70 was highest in juvenile localized scleroderma (LS; 4/29, 13.8%), juvenile dermatomyositis (JDM; 2/11, 18.2%), childhood systemic lupus erythematosus (cSLE; 19/331, 5.7%), diffuse cutaneous systemic sclerosis (1/22, 4.5%), celiac disease (2/49, 4.1%), and juvenile idiopathic arthritis (JIA; 5/202, 2.5%). Of note, anti-DFS70 antibodies were observed in 3/26 children (11.5%) with uveitis and JIA-associated uveitis. Conclusion. The frequency of anti-DFS70 autoantibodies in healthy pediatric subjects is within the lower range of that reported in adults. Anti-DFS70 antibodies can be found in childhood SSc and cSLE, but has a remarkably high frequency in children with LS, JDM, and uveitis.