Kristiina Aalto

Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis

OBJECTIVEnTo evaluate the efficacy of adalimumab in juvenile idiopathic arthritis (JIA)-associated uveitis.nnnMETHODSnRetrospective observational study of 20 patients with JIA and chronic uveitis on adalimumab treatment. The ocular inflammation and improvement was assessed according to the Standardization of Uveitis Nomenclature criteria.nnnRESULTSnAt the initiation of adalimumab, the mean age of patients was 13.4 yrs and the mean duration of uveitis 8.7 yrs. Seventeen (85%) patients had polyarticular JIA and 19 (95%) had previously been on anti-TNF treatment. The mean duration of adalimumab therapy was 18.7 months. Of the 20 patients, 7 (35%) showed improved activity, 1 (5%) worsening activity and in 12 (60%) no change was observed in the activity of uveitis. Those with improved activity were younger and had shorter disease duration. The mean number of flares/yr decreased from 1.9 to 1.4 during adalimumab treatment. Serious adverse events or side-effects were not observed. Seven patients discontinued adalimumab during the follow-up: six because of inefficacy and one because of inactive uveitis.nnnCONCLUSIONnAdalimumab is a potential treatment option in JIA-associated uveitis, even in patients non-responsive to previous other anti-TNF therapy.

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.

Complementary and alternative medicine use in adolescents with inflammatory bowel disease and juvenile idiopathic arthritis

BackgroundThe use of complementary alternative medicine (CAM) is potentially prevalent among paediatric patients with chronic diseases but with variable rates among different age groups, diseases and countries. There are no recent reports on CAM use among paediatric patients with inflammatory bowel disease (IBD) and juvenile idiopathic arthritis (JIA) in Europe. We hypothesized that CAM use associates with a more severe disease in paediatric IBD and JIA.MethodsA cross-sectional questionnaire study among adolescent outpatients with IBD and JIA addressing the frequency and type of CAM use during the past year. The patients were recruited at the Children’s Hospital, University of Helsinki, Finland.ResultsOf the 147 respondents, 97 had IBD (Crohn’s disease: nu2009=u200946; median age 15.5, disease duration 3.4xa0years) and 50 had JIA (median age 13.8, disease duration 6.9xa0years). During the past 12xa0months, 48% regularly used CAM while 81% reported occasional CAM use. Compared to patients with JIA, the use of CAM in IBD patients tended to be more frequent. The most commonly used CAM included probiotics, multivitamins, and mineral and trace element supplements. Self-imposed dietary restrictions were common, involving 27.6% of the non-CAM users but 64.8% of all CAM users. Disease activity was associated with CAM use in JIA but not in IBD.ConclusionsCAM use is frequent among adolescents with IBD and JIA and associates with self-imposed dietary restrictions. Reassuringly, adherence to disease modifying drugs is good in young CAM users. In JIA, patients with active disease used more frequently CAM than patients with inactive disease. As CAM use is frequent, physicians should familiarise themselves with the basic concepts of CAM. The potential pharmacological interaction or the toxicity of certain CAM products warrants awareness and hence physicians should actively ask their patients about CAM use.

Finding specific 10-joint Juvenile Arthritis Disease Activity Score (JADAS10) and clinical JADAS10 cut-off values for disease activity levels in non-systemic juvenile idiopathic arthritis: a Finnish multicentre study

OBJECTIVESnTo establish the cut-off values for inactive disease, as well as low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA) in non-systemic JIA based on the Juvenile Arthritis Disease Activity Score (JADAS) and assessed with the 10-joint JADAS (JADAS10) and clinical JADAS10 (cJADAS10).nnnMETHODSnIn a multicentre cross-sectional study consisting of ∼20% of all patients with JIA in Finland (n = 509), we obtained data on their most recent registered visits between January 2013 and January 2014. We calculated the JADAS10 and cJADAS10 and established the cut-off values of both of these scores using two different receiver operating characteristics-based statistical methods.nnnRESULTSnOf the 509 patients studied, 65.8% were females and 53.8% had polyarticular disease. The most suitable method for determining cut-off values was the Youden index. In oligoarticular patients, a JADAS10 score of 0-0.5 represented inactive disease, 0.6-2.7 LDA and ≥2.8 MDA. In polyarticular disease, a JADAS10 score of 0-0.7 represented inactive disease, 0.8-3.9 LDA and ≥4.0 MDA. The cut-off values for HDA were not possible to establish because only two visits fulfilled HDA criteria.nnnCONCLUSIONnWe established cut-off values for LDA and MDA. A reliable definition for HDA will require more patients. In the clinical setting, both the cJADAS10 and JADAS10 serve equally well both for research and quality control purposes. In the future, uniform clinical disease activity levels should be established. We also suggest revising and validating the criteria for HDA. Valid and robust cut-off values for disease activity levels can guide both clinicians and researchers and equip them for quality control.

Gluten-Free Diet in Juvenile Idiopathic Arthritis

Aim: Gluten-free diet may attenuate joint symptoms in adult rheumatoid arthritis. We conducted a groundwork study on the effect of a gluten-free diet in children with arthritis. Methods: 4 children (aged 5-12) with juvenile idiopathic arthritis (JIA) were recruited for a study including 3 months on a gluten-free diet. Articular symptoms and signs, and the presence of antibodies to gliadin, endomysium, transglutaminase, and milk were determined at 0, 3, and 6 months as well as immunoglobulins, blood count, ESR, CRP and markers for intestinal inflammation, alpha-1-antitrypsin, physician’s and patient’s VAS, a CHAQ-form, and JADAS10. Results: In a 5-year old boy articular and gastrointestinal symptoms improved during gluten-free diet. A 12-year old girl experienced some relief and disease activity scores showed moderate improvement. In two other patients the objective measurements were unaltered. In one of these two, antigliadin-IgG and milk-IgA antibodies remained elevated throughout the study. Conclusions: Results of this small prospective study on gluten free diet in patients with JIA were inconclusive although some subjective improvement was observed. A more extensive study including patients with more active disease seems warranted.

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.

Defining new clinical derived criteria for high disease activity in non-systemic juvenile idiopathic arthritis: a Finnish multicentre study

Abstract Objectives To redefine criteria for high disease activity (HDA) in JIA, to establish HDA cut-off values for the 10-joint Juvenile Arthritis Disease Activity Score (JADAS10) and clinical JADAS10 (cJADAS10) and to describe the distribution of patients’ disease activity levels based on the JADAS cut-off values in the literature. Methods Data on 305 treatment-naïve JIA patients were collected from nine paediatric units treating JIA. The median parameters of the JADAS were proposed to be the clinical criteria for HDA. The cut-off values were assessed by using two receiver operating characteristics curve–based methods. The patients were divided into disease activity levels based on currently used JADAS cut-off values. Results We proposed new criteria for HDA. At least three of the following criteria must be satisfied in both disease courses: in oligoarthritis, two or more active joints, ESR above normal, physician global assessment (PGA) of disease activity ≥2 and parent/patient global assessment (PtGA) of well-being ≥2; in polyarthritis, six or more active joints, ESR above normal, PGA of overall disease activity ≥4 and PtGA of well-being ≥2. The HDA cut-off values for JADAS10 (cJADAS) were ≥6.7 (6.7) for oligoarticular and ≥15.3 (14.1) for polyarticular disease. The distribution of the disease activity levels based on the JADAS cut-off values in the literature varied markedly based on which cut-offs were used. Conclusion New clinically derived criteria for HDA in JIA and both JADAS and cJADAS cut-off values for HDA were proposed.

Fecal calprotectin in juvenile idiopathic arthritis patients related to drug use

BackgroundPatients with juvenile idiopathic arthritis (JIA) on non-steroidal anti- inflammatory drugs (NSAIDs) may experience abdominal pain. In adults, NSAID use has been linked to an increase in fecal calprotectin (FC) levels, a surrogate marker for gut inflammation. In JIA, data on gut inflammation related to drug use is scarce.MethodsJIA patients followed up at the outpatient pediatric rheumatology clinic in Children’s Hospital, Helsinki University Hospital, Helsinki, Finland were routinely assessed for FC if they complained about abdominal pain, had an elevated erythrocyte sedimentation rate (ESR) or used NSAIDs on a daily basis. The FC levels were related to the presence of abdominal pain, to ESR, and to the presence of HLA-B27.ResultsOf the total group of 90 patients (median age 9.1 years; 45 JIA patients with disease modifying anti-rheumatic drugs (DMARDs), 25 without DMARD medication, and 20 arthralgia patients as controls), approximately 50% used NSAIDs, of whom 40% complained about abdominal pain. In patients with abdominal pain, one-third had elevated FC values (>100 μg/g). The FC values, for the most part, declined along with the discontinuation or reduction of NSAIDs and after intensifying the DMARD medication, where after the pain disappeared. In patients with an elevated ESR, the FC values and ESR normalized in parallel. The presence of HLA-B27 was not associated with FC levels.ConclusionIn patients with JIA and abdominal pain, it may be useful to determine the FC when evaluating the need for further gastrointestinal examinations.

THU0516 Health-Related Quality of Life in Patients with Newly Diagnosed JIA with Different Treatment Strategies (Acute-JIA Study): Table 1.

Background Health-related quality of life (HrQoL) is impaired in patients with juvenile idiopathic arthritis (JIA). Objectives To study HrQoL in patients with newly diagnosed JIA on three treatment strategies. Methods In ACUTE-JIA Study (1), 60 patients were randomized into three treatment arms: infliximab with methotrexate (TNF); a combination of methorexate, hydroxychloroquine, and sulphasalazine (COMBO), or methotrexate monotherapy (MTX). During the first year, at seven study visits, efficacy was measured with ACRped criteriae and HrQoL with Child Health Questionnaire (CHQ). Results All 20 patients continued intended therapy until week 54 in the TNF, 16 in COMBO, and 11 in MTX group. The last CHQ scores before discontinuation of the therapy were carried forward. Physical summary scores (PhS) and Psychosocial summary scores (PsS) improved from week 0 to 54 (Table 1) in all treatment groups with no differences between the groups. In all groups, significant improvements in PhS occurred over time until week 24 of the study, but not after that. In univariate analyses, CHAQ at weeks 0 (β=20.07; p<0.001) and 12 (β=-14.75; p=0.04), and cumulative use of steroids (β=-3.89; p=0.006) correlated with absolute change in PhS from week 0 to 54 (R2=0.381). Table 1. Psychosocial Summary scores (PsS) and Physical Summary scores (PhS) (median [range]) at onset (0) and at week 54 All Anti-TNF COMBO MTX p PsS0 52.63 [27.11-65.84]* 54.47 [27.11-58.53] 47.64 [37.08-62.64] 53.02 [40.23-65.84] 0.28 PsS54 54.62 [40.60-64.61] 55.13 [45.38-65.61] 55.58 [40.60-62.79] 53.84 [44.20-63.77] 0.98 PhS0 27.30 [-19.29-59.17]* 25.65 [10.52-51.82] 31.17 [-19.29-59.17] 19.49 [-6.41-51.11] 0.61 PhS54 51.69 [-2.21-65.81] 54.31 [13.34-62.81] 52.68 [0-62.87] 47.14 [6.35-65.18] 0.37* PsS0 vs PsS54 p<0.001; PhS0 vs PhS54 p<0.001 Wilcoxon signed rank test. Conclusions During the first year of treatment of JIA, HrQoL improved in all treatment categories. Patients and parents seem to acknowledge a significant change in PhS during the first half-year, but not thereafter. References Tynjälä P, Vähäsalo P, Tarkiainen M, et al. Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011 Sep;70(9):1605-12. Disclosure of Interest None declared

Finding specific cut-off values of JADAS-10 and JADAS3-10 for disease activity levels in juvenile idiopathic arthritis: a finnish multicenter study

It’s crucial to observe the changes in disease activity in JIA in order to investigate reliably the effects of the new treatments and to optimize their use. Several tools for outcome measurements have been developed. Juvenile Arthritis Disease Activity Score (JADAS) is an independent measure of the treatment response and enables the comparison between cohorts. However, the use of ESR restricts the feasibility of JADAS. That’s why a JADAS index excluding ESR has been tested (JADAS3). In order to simplify the interpretation of the JADAS score, efforts have been made to define cut-off values of JADAS for low and high diease activity. Cut-off values of JADAS for disease activity levels, as defined by ACR, have not been developed. Neither have any cut-off values for JADAS3 been defined.