Effects of adherence to treatment on short‐term outcomes in children with juvenile idiopathic arthritis

Objective

To determine the impact of adherence to treatment (medication and prescribed exercise) on outcomes in children with juvenile idiopathic arthritis (JIA).

Methods

In this longitudinal study, we studied parents of patients with JIA at the Montreal Children's Hospital and British Columbia Children's Hospital in Vancouver. Adherence was evaluated on a visual analog scale in the Parent Adherence Report Questionnaire. Outcomes of interest were active joint count, pain, child functional score on the Child Health Assessment Questionnaire, quality of life score on the Juvenile Arthritis Quality of Life Questionnaire, and parental global impression of overall well‐being. The association between adherence to treatment and subsequent outcomes was evaluated using generalized estimating equations and logistic regression.

Results

Mean age and disease duration of our sample of 175 children were 10.2 and 4.1 years, respectively. Moderate adherence to medication was associated with lower active joint count (odds ratio [OR] 0.47, 95% confidence interval [95% CI] 0.22–0.99). Moderate adherence to exercise was associated with better functional score (OR 0.13, 95% CI 0.03–0.54), and lower pain during the last week (OR 0.14, 95% CI 0.04–0.50). Both high and moderate adherence to exercise were associated with parental perception of global improvement.

Conclusion

Improved outcomes in patients who adhered to treatment underscores the need for clinicians to address adherence issues with their patients. Sustaining adherence, particularly to the more time‐consuming treatment of exercise, is a challenge.     

Comparison between children with juvenile idiopathic arthritis and their parents concerning perceived treatment adherence

OBJECTIVE: Adherence to treatment in juvenile idiopathic arthritis (JIA) may be associated with better outcomes. Clinicians must be aware of possible divergence between parents and children regarding adherence, in order to gain a better understanding of adherence and factors associated with it. The objective was to determine the level of agreement between children with JIA and their parents concerning perception of the child's adherence to the treatment regimen (for both medications and exercises). METHODS: Fifty patients and their parents, who attended the JIA clinic at the Montreal Children's Hospital, completed the Child Adherence Report Questionnaire and the Parent Adherence Report Questionnaire. Paired t-tests were used to compare parents' and children's scores for adherence questions and agreements were analyzed by intraclass correlation coefficients (ICCs). RESULTS: Parents reported that their children showed more negative reactions to taking medication and doing exercises, more helpfulness from the medication, and more difficulty to carry out the exercise program than their children reported. ICCs (95% confidence interval) for medications and exercises were, respectively, 0.32 (0.04, 0.56) and 0.77 (0.61, 0.87) for overall adherence, 0.33 (0.05, 0.57) and 0.39 (0.09, 0.62) for perceived difficulty to following treatment, and 0.37 (0.09, 0.60) and 0.45 (0.17, 0.67) for how often children had negative reactions following treatment. Levels of agreement for perceived helpfulness of treatments were quite low. CONCLUSION: Agreement between parents and children concerning adherence was at best moderate, and generally better for the exercise program than for prescribed medications.     

Perceived adherence to prescribed treatment in juvenile idiopathic arthritis over a one-year period

OBJECTIVE: To document perceived adherence to treatment (taking medications and performing exercises) in patients with juvenile idiopathic arthritis (JIA) over a 1-year period and to identify related factors. METHODS: We surveyed parents of patients with JIA at the Montreal Children's Hospital and British Columbia's Children's Hospital in Vancouver. Parents were asked to respond to a series of questionnaires every 3 months over a 12-month period. Perceived adherence was evaluated on a 100-mm visual analog scale (VAS) in the Parent Adherence Report Questionnaire (PARQ). Parental coping, distress, child function, disease severity and duration, perceived helpfulness of treatment, problems encountered, and sociodemographic data were also assessed. RESULTS: The mean age of our sample of 175 children was 10.2 years; mean age at diagnosis was 6.1 years and mean disease duration was 4.1 years. Perceived adherence to medications was consistently high, with average adherence at baseline, 3, 6, 9, and 12 months being 86.1, 91.7, 90.4, 92.0, and 88.8, respectively, on the PARQ VAS. Perceived adherence to exercise was lower but remained steady, with corresponding means of 54.5, 64.1, 61.2, 63.0, and 54.3, respectively. Using generalized estimating equation analysis, factors associated with higher perceived adherence to medications included perceived helpfulness of medications and lower disease severity; those associated with higher perceived adherence to exercise were younger age of the child, child involvement in responsibility for treatment, and higher perceived helpfulness of the treatment. CONCLUSION: Belief in helpfulness of treatment is associated with higher parental perceived adherence to treatment.     

Gower's sign in children with juvenile idiopathic arthritis

SIR, One clinical sign assessing proximal leg muscle weaknessis Gower's sign, the most important feature of which is theadoption of a prone position before standing. This can be seenduring normal development in toddlers up to the age of 36 months;only 6.5% of healthy children over 3 yr still roll prone duringstanding, while children with neuromuscular disorders have apositive early Gower's sign that persists after the age of 3yr [1]. Previous research in our     

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.     

Etanercept treatment improves longitudinal growth in prepubertal children with juvenile idiopathic arthritis

OBJECTIVE: Anti-tumor necrosis factor (TNF) therapy is known to decrease disease activity of juvenile idiopathic arthritis (JIA), but its effect on longitudinal growth in relation to puberty is not clear. We studied longitudinal growth in response to etanercept treatment in prepubertal and pubertal patients with JIA. METHODS: Out of 52 children treated with etanercept, we studied 20 prepubertal and 11 early/midpubertal patients adherent to treatment for at least 1 year. We collected data on growth and glucocorticoid medication and calculated each patient's height standard deviation score (SDS) in relation to the mid-parental height, the change of this value (DeltahSDS) from 1 to 0 and 0 to 1 year of treatment, and the change between the DeltahSDS values to assess growth improvement. RESULTS: In the prepubertal group, the relative height SDS (mean +/- standard error of the mean) was 1.8 +/- 0.2, 2.1 +/- 0.3, and 1.9 +/- 0.3, and in the pubertal group 1.1 +/- 0.4, 1.3 +/- 0.3, and 1.1 +/- 0.3 at 1, 0, and +1 year of treatment, respectively. The DeltahSDS before etanercept was 0.3 +/- 0.1 in prepubertal and 0.2 +/- 0.2 in pubertal patients. Over the first year with etanercept, DeltahSDS was +0.2 +/- 0.1 in prepubertal (p = 0.001 vs before etanercept; paired Student t-test) and +0.2 +/- 0.1 in pubertal patients (p = 0.071). Nevertheless, most prepubertal (17/20) and pubertal (8/11) patients had improved growth (DeltahSDS) in response to etanercept treatment when analyzed individually. The need for intraarticular glucocorticoid injections was negatively correlated to the improved growth (p = 0.001). CONCLUSION: TNF inhibition with etanercept improved growth in a majority of patients with JIA. Our data demonstrate that growth improvement with etanercept was independent of the pubertal growth spurt.     

Oral health of children with juvenile idiopathic arthritis

OBJECTIVE:s. To estimate dental disease indices and temporomandibular joint (TMJ) dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS: Indices were recorded for dental caries, bacterial dental plaque, gingival inflammation, and TMJ dysfunction in children with JIA and matched controls. RESULTS: There was no significant difference in dental caries experience or the mean plaque score between children with JIA and controls. The mean gingivitis score for the permanent teeth only was significantly greater in the JIA children compared with the controls (p = 0.02). There was a significantly greater proportion of children with JIA with signs of both left and right TMJ dysfunction (p = 0.05, p = 0.02) and symptoms (p = 0.0001, p = 0.0001) compared with controls. CONCLUSION: The low caries rate was attributed to the fact that children with JIA had received preventive dental care from an early age combined with sugar free medication.     

Clinical analysis in 202 children with juvenile idiopathic arthritis

This study attempts to characterize the clinical features of various subtypes of juvenile idiopathic arthritis (JIA) and try to investigate the prognostic factors. Patients with JIA hospitalized in Nanjing Children Hospital during April 2005 to April 2010 were enrolled. Clinical manifestations and laboratory parameters were retrospectively reviewed. A total of 202 cases were included, 105 males and 97 females, with average age at onset of 7.5 years. Patients with systemic JIA were most common, accounting for 47.0 %. Fever, rash, and arthritis were the most common clinical manifestations. The most commonly involved joints were the knee and ankle. Laboratory parameters were significantly different but not specific. Time from onset to treatment, hepatomegaly, and involvement of wrist may have a significant effect on the outcome. A total of 117 cases were followed up, with an average follow-up time of 2 years. Among them, 55 cases achieved complete remission, 27 cases with partial remission, and 29 cases without remission, and six died. JIA is a heterogeneous disease with varied onset and clinical manifestations, which makes treatment a serious challenge. Receiving treatment late, hepatomegaly, and impaired wrist were early risk factors for an unfavorable outcome.     

Perceived adherence to prescribed treatment in juvenile idiopathic arthritis over a one‐year period

Objective

To document perceived adherence to treatment (taking medications and performing exercises) in patients with juvenile idiopathic arthritis (JIA) over a 1‐year period and to identify related factors.

Methods

We surveyed parents of patients with JIA at the Montreal Children's Hospital and British Columbia's Children's Hospital in Vancouver. Parents were asked to respond to a series of questionnaires every 3 months over a 12‐month period. Perceived adherence was evaluated on a 100‐mm visual analog scale (VAS) in the Parent Adherence Report Questionnaire (PARQ). Parental coping, distress, child function, disease severity and duration, perceived helpfulness of treatment, problems encountered, and sociodemographic data were also assessed.

Results

The mean age of our sample of 175 children was 10.2 years; mean age at diagnosis was 6.1 years and mean disease duration was 4.1 years. Perceived adherence to medications was consistently high, with average adherence at baseline, 3, 6, 9, and 12 months being 86.1, 91.7, 90.4, 92.0, and 88.8, respectively, on the PARQ VAS. Perceived adherence to exercise was lower but remained steady, with corresponding means of 54.5, 64.1, 61.2, 63.0, and 54.3, respectively. Using generalized estimating equation analysis, factors associated with higher perceived adherence to medications included perceived helpfulness of medications and lower disease severity; those associated with higher perceived adherence to exercise were younger age of the child, child involvement in responsibility for treatment, and higher perceived helpfulness of the treatment.

Conclusion

Belief in helpfulness of treatment is associated with higher parental perceived adherence to treatment.     

Hepatitis B vaccination in children with juvenile idiopathic arthritis

OBJECTIVES: To evaluate the responsiveness of children with juvenile idiopathic arthritis (JIA) to hepatitis B vaccination and to determine the most useful vaccination schedule. METHODS: 39 children with JIA were enrolled in the study; all were in remission and negative to serological testing for hepatitis B surface antigen (HbsAg). The control group consisted of 41 healthy children. There were two different vaccination schedules: group I was vaccinated at 0, 1, and 3 months; group II was vaccinated at 0, 1, and 6 months. Positive responsiveness to the vaccine was defined as an anti-hepatitis B antibody titre above 10 mIU/ml. RESULTS: All the children except one with systemic JIA developed an antibody response. None of the JIA patients experienced a flare up or clinical deterioration related to the vaccination. The antibody levels in children with JIA were significantly lower than in the healthy controls. Comparison of the antibody levels between the two vaccination schedules showed no statistical difference in the controls; in the JIA subjects the group II schedule resulted in a trend to a greater response than the group I schedule (p<0.07). Vaccine responsiveness was not influenced by either methotrexate or prednisolone treatment. CONCLUSIONS: Children with JIA had an adequate response to hepatitis B vaccination and the response was not affected by immunosuppressive treatment. A vaccination schedule at 0, 1, and 6 months seems to be preferable to 0, 1, and 3 months.     

Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.     

Improvement of functional ability in children with juvenile idiopathic arthritis by treatment with etanercept

The objective of the study is to investigate the functional ability, i.e., the physical aspect of the health-related quality of life and its determining factors during therapy with etanercept in children with juvenile idiopathic arthritis (JIA). Assessment of the Child Health Assessment Questionnaire (CHAQ), the number of active joints, duration of morning stiffness, ESR, C-reactive protein, parent’s global assessment of the overall patient’s well-being, physician’s global assessment of the overall disease activity, concomitant treatment with methotrexat, number of aids/devices needed, and calculation of the PedACR-score. Data of 437 children were analyzed for disease severity and impact of the disease on functional abilities. Data of 114 children with a complete data set and a continuous treatment for at least 24 months were used for analysis of the impact of treatment on functional abilities. Before treatment with etanercept, patients with systemic arthritis and seropositive or seronegative polyarthritis were disabled more heavily than those with other subtypes of JIA. There was a correlation between high CHAQ scores and the number of active joints, aids/devices needed, parent’s global assessment of the overall patient’s well-being, morning stiffness, physician’s global assessment of the overall disease activity, and C-reactive protein (P < 0.005). Of the eight areas, “dressing and grooming”, “arising”, “eating”, “walking”, “hygiene”, “reach”, “grip” and “activities”, the latter was most severely affected. 96.5, 93.8, and 90.3% of the patients reached a PedACR-30, -50 and -70 score upon treatment with etanercept for 24 months. The areas of eating and walking were best before therapy and showed highest improvement with therapy. Under therapy with etanercept patients of all JIA subgroups significantly improved their functional ability (P < 0.0001), but patients with polyarthritis less frequently improved their physical functioning. Disease activity and the physical aspect of health-related quality of life including functional ability improved significantly during therapy with etanercept in children with JIA. Duties of everyday life were easier to accomplish.     

Long-term outcomes and predictors of outcomes for patients with juvenile idiopathic arthritis

Prediction of the long-term outcome for patients with juvenile idiopathic arthritis requires assessment of disability, psychosocial and socioeconomic function. Measures for the first have evolved from Steinbrocker functional classifications to validated self-administered questionnaires. The proportion of patients with severe disability has decreased during the past three decades but significant numbers of patients enter adulthood with some disability detected with the newer measures. Despite careful study, few early predictors of a poor outcome have been identified. The most consistent are early age at onset, persistent fever and thrombocytosis in patients with systemic juvenile idiopathic arthritis. Reports of psychosocial and socioeconomic outcomes are controversial and further analyses of these spheres are required. An increased risk of osteoporosis and osteopenia has been reported in adults with juvenile idiopathic arthritis. The most significant problem faced by patients during adulthood is persistent disease activity as disability, radiographic damage and the risk of osteoporosis all increase with increasing duration of disease.     

Effects of long‐term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis

Objective

To evaluate the effects of long‐term etanercept treatment, with or without methotrexate, on growth in children with selected categories of juvenile idiopathic arthritis (JIA).

Methods

We conducted a 3‐year, open‐label, nonrandomized registry of 594 patients with polyarticular or systemic JIA treated with etanercept only, etanercept plus methotrexate, or methotrexate only. Height, weight, and body mass index (BMI) were assessed at baseline and at years 1, 2, and 3, using percentiles derived from US Centers for Disease Control and Prevention standardized growth charts.

Results

Statistically significant increases in the mean height percentiles from baseline were observed in etanercept‐treated patients at year 3 (4.8 percentile points) and in patients treated with etanercept plus methotrexate at years 1, 2, and 3 (2.4, 3.3, and 5.6 percentile points, respectively). Statistically significant increases from baseline in the mean weight percentiles were observed at years 1, 2, and 3 in both the etanercept group (7.4, 10.0, and 13.0 percentile points) and the etanercept‐plus‐methotrexate group (2.9, 6.9, and 8.4 percentile points, respectively). Statistically significant increases from baseline in the mean BMI percentiles were observed in both the etanercept group (range 9.6–13.8 percentile points) and the etanercept‐plus‐methotrexate group (range 2.1–5.2 percentile points). The mean height, weight, and BMI percentiles did not change significantly in patients in the methotrexate‐only group.

Conclusion

Etanercept treatment, with or without methotrexate, may contribute to the restoration of normal growth in children with JIA.

     

Effects on growth and body composition of growth hormone treatment in children with juvenile idiopathic arthritis requiring steroid therapy

OBJECTIVE: Decreased growth velocity and abnormal body composition including severe osteoporosis are common in glucocorticoid-treated patients with juvenile idiopathic arthritis (JIA). We evaluated the effects of recombinant human growth hormone (GH) given for 3 years on growth velocity, height standard deviation score (SDS), and body composition, together with potential adverse effects on glucose tolerance. METHODS: Thirteen patients received GH (0.46 mg/kg/week) for 3 years. Body composition was assessed by dual-energy x-ray absorptiometry and glucose tolerance by annual oral glucose tolerance tests. RESULTS: Median growth velocity increased from 2.1 to 6.0 cm/year (p = 0.002) in the first year and remained higher than baseline in the second year of treatment. Height SDS did not change significantly (-4.6 SDS at baseline vs -4.3 SDS at study completion), but the growth response varied markedly across patients. Compared with baseline, lean mass increased by 33%, fat mass remained stable, and lumbar bone mineral density increased by 36.6%. Transient glucose intolerance developed in 6 patients, but glycosylated hemoglobin concentrations did not change significantly and diabetes mellitus did not occur. CONCLUSION: Treatment with GH restored linear growth without inducing catch-up growth, significantly improved body composition, and prevented further bone loss. Prolonged followup is needed to assess the benefits of GH and longterm consequences of hyperinsulinism.     

Safety of anti-TNFalpha therapy in children with juvenile idiopathic arthritis

Anti-TNFalpha agents are frequently used in the treatment of severe JIA. Etanercept, a fully human soluble recombinant tumour necrosis factor p75 receptor Fc fusion protein, has been registered for the treatment of polyarticular course JIA patients who fail to respond to or do not tolerate methotrexate (MTX). Infliximab, a chimeric human-mouse monoclonal antibody to TNFalpha, is expected to be registered soon for JIA and Crohn's disease (CD) in children. As in adults, both agents are effective in controlling inflammation and inhibiting the progression of joint destruction. Despite this good clinical efficacy, the physician must remain alert for potential side effects, especially after prolonged use. This review gives an overview of the reported adverse events.