Clinical Outcome and Long-term Remission in JIA.

PURPOSE OF REVIEW: This review assesses the long-term remission and predictors of clinical outcome in patients with juvenile idiopathic arthritis (JIA). A comprehensive literature search was performed including articles published between January 1, 2004 and February 28, 2017. Studies, with a minimum follow-up of 24 months, were selected independently by two reviewers based on in- and exclusion criteria. The objective outcome was inactive disease/clinical remission as defined by the Wallace criteria at last follow-up. RECENT FINDINGS: The probability of achieving inactive disease and/or clinical remission is dependent on the JIA subcategories studied in the different articles. Overall, a significant proportion of JIA patients still showed signs of active disease at last follow-up. Some studies include patient populations followed for 15 years or more and these patients were exposed to different treatment protocols at disease presentation than patients diagnosed in the biologic era. Although the severity of the morbidity and associated mortality risk has decreased over time, a significant proportion of the current JIA patients still do not reach an inactive disease status within a 2-year follow-up window. Studying the long-term outcome of patients with JIA remains challenging due to the heterogeneity of the study designs and study populations. Although improvement has been shown in the biologic era, we still need to enhance the number of patients with inactive disease within the first 2 years after diagnosis.

Remission rate is not dependent on the presence of antinuclear antibodies in juvenile idiopathic arthritis.

Recently, it has been hypothesized that the subcategories of the ILAR classification of juvenile idiopathic arthritis (JIA) are not homogeneous, and that the presence of antinuclear antibodies (ANA) should lead to a separate entity. Therefore, the aim of this study was to evaluate ANA positivity as a predictor of achieving remission. A retrospective single-center cohort study including all JIA patients diagnosed between January 2000 and May 2014. A minimum follow-up of 1 year was required plus the ANA status. ANA positivity was defined as at least two positive results with a titer ≥1:160. Demographic and clinical features were collected. Remission at last follow-up was defined by the Wallace criteria. A total of 625 patients met the inclusion criteria and 230 (37%) were found ANA positive. Analysis showed no difference in remission rate between ANA-positive and ANA-negative patients. Additionally, joint count at diagnosis and at last follow-up were comparable in both groups. ANA positivity was correlated to a female predominance and young age at diagnosis (p < 0.001). Remission rates are not different in ANA-positive patients than in ANA-negative patients. This does not support the hypothesis to possibly divide JIA patients based on their ANA status.

Accelerometer-assessed daily physical activity in relation to pain cognition in juvenile idiopathic arthritis.

OBJECTIVES: Pain has been known to predict low physical activity (PA) in juvenile idiopathic arthritis (JIA) and high levels of pain are related to maladaptive coping rather than disease severity. Objectively monitored PA in JIA has recently been shown not to be related to pain intensity, emphasizing the need to explore pain more deeply. The aim of this study was to examine accelerometer-assessed PA in relation to pain cognition in children with JIA. METHOD: Data gathered included disease activity, functional ability, and pain cognition. PA was monitored with a GT1M Actigraph accelerometer. RESULTS: Sixty-one patients were included. Disease activity, functional impairment, and pain intensity scores were relatively low. Accelerometry was correlated positively to the specific belief of having control of pain ('Control') but negatively to disease activity. There was no correlation with functional ability, pain intensity, coping strategies, or other pain beliefs. When isolated, disease activity (measured by the 27-joint count Juvenile Arthritis Disease Activity Score, JADAS-27) contributed significantly to the variance in accelerometry, while 'Control' could not significantly explain a unique part of the variance. CONCLUSIONS: Objectively measured PA was negatively correlated to disease activity but not to pain intensity. The only pain cognition measurement to reach higher levels of PA was to be in control of pain.

Accelerometry-based monitoring of daily physical activity in children with juvenile idiopathic arthritis.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) may cause functional impairment, reduced participation in physical activity (PA) and, over time, physical deconditioning. The aim of this study was to objectively monitor daily free-living PA in 10-16-year-old children with JIA using accelerometry with regard to disease activity and physical variables and to compare the data with those from healthy age- and gender-matched controls. METHOD: Patients underwent an evaluation of disease activity, functional ability, physical capacity, and pain. Accelerometer monitoring was assessed using the GT1M ActiGraph. Normative data from two major studies on PA in Danish schoolchildren were used for comparison. RESULTS: Data of accelerometry were available for 61 JIA patients and 2055 healthy controls. Of the JIA patients, 57% showed below-average values of maximal physical capacity (fitness level). JIA patients showed low disease activity and pain and were physically well functioning. Accelerometer counts were lower in JIA patients than in controls. Accelerometer measurements were negatively correlated with disease activity, erythrocyte sedimentation rate (ESR), and number of joints with swelling and/or limited range of motion (ROM). No correlation was found between PA and pain scores, functional ability, and hypermobility. Patients with involvement of ankles or hips demonstrated significantly lower levels of PA. CONCLUSIONS: Children with JIA are less physically active and have lower physical capacity and fitness than their age- and gender-matched healthy peers despite good disease control. The involvement of hips or ankles is associated with lower PA.

Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis.

OBJECTIVE: To evaluate changes in health-related quality of life (HRQoL) in patients with refractory juvenile idiopathic arthritis (JIA) who are being treated with etanercept. METHODS: 53 patients with JIA from seven Dutch centres were included. HRQoL was measured by the Childhood Health Assessment Questionnaire (CHAQ), Child Health Questionnaire (CHQ) and Health Utilities Index mark 3 (HUI3) at the start and after 3, 15 and 27 months of treatment. At the same time points the following JIA disease activity variables were collected; physician's global assessment through the visual analogue scale (VAS), number of active and limited joints and erythrocyte sedimentation rate. A statistical method linear mixed models was used to assess outcomes over time. RESULTS: During etanercept treatment both disease-specific and generic HRQoL outcomes improved dramatically. Significant improvements were shown after 3 months and these improvements continued at least up to 27 months of treatment. The disease-specific CHAQ, including VAS pain and wellbeing, showed a significant improvement in all domains. The generic health-profile measure CHQ improved for all the health concepts except for "family cohesion", which was normal. The generic preference-based HUI3 showed impairment and, subsequently, significant improvement in the more specific domains ("pain", "ambulatory", "dexterity"). In accordance disease activity variables also improved significantly over time. CONCLUSION: This study shows that the HRQoL of patients with refractory JIA can be substantially improved by the use of etanercept for all aspects impaired by JIA. Information on HRQoL is crucial to understand the complete impact of etanercept treatment on patients with JIA and their families.

Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register.

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).

Development of a web-based register for the Dutch national study on biologicals in JIA: www.ABC-register.nl.

OBJECTIVES: Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study. METHODS: We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data. RESULTS: The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved. CONCLUSIONS: By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

Incidence of temporomandibular involvement in juvenile idiopathic arthritis.

OBJECTIVE: Temporomandibular joint (TMJ) involvement is a frequent feature in cross-sectional prevalence studies among juvenile idiopathic arthritis (JIA) patients. The cross-sectional design makes it almost impossible to study the incidence. Follow-up data on TMJ involvement are sparse. In this study patients were reviewed with an interval of a minimum of 1 year and a maximum of 2 years to study the yearly incidence of TMJ involvement and to obtain follow-up data on TMJ involvement and orthopantomogram (OPT) alterations. METHODS: Children with JIA from a previous study on TMJ involvement were included. OPTs were scored according to Rohlin's grading system (grade 0-5). A paediatric rheumatologist measured the level of disease activity during the interval. RESULTS: Eighty-nine of the 97 patients were included in this study with a mean follow-up of 14 months. The yearly incidence of TMJ involvement was 7.1% in patients with JIA. Improvement on the OPT was seen in 27 patients (66%), and 19 of these patients no longer showed any signs of TMJ involvement. Worsening on the OPT was seen in four patients (10%). Disease activity was significantly lower in the improved patients than in the patients with worsening. CONCLUSION: Condylar lesions due to arthritis can improve over time, indicating a regenerative capacity of the mandibular condyle. As condylar improvement seems to be associated with low disease activity, it is important to consider the TMJ when deciding on a therapeutic regimen.

Facioskeletal changes in children with juvenile idiopathic arthritis.

OBJECTIVE: To investigate the facioskeletal morphology in patients with juvenile idiopathic arthritis (JIA) with and without temporomandibular joint (TMJ) involvement. METHODS: Eighty five patients were included. TMJ involvement was defined by orthopantomogram alterations. Lateral cephalograms were used to determine linear and angular measurements and occlusion. RESULTS: Patients regardless of their TMJ status had a 67% chance for retrognathia and a 52% chance for posterior rotation of the mandible and, respectively, 82% and 58% if TMJ involvement were present. Changes were not uniformly distributed among the different subtypes. CONCLUSION: Patients with JIA have an altered facial morphology, especially in the presence of TMJ involvement.