Nicoletta Solari

Development and validation of a preliminary definition of minimal disease activity in patients with juvenile idiopathic arthritis

OBJECTIVE To develop and validate a definition of minimal disease activity (MDA) in patients with juvenile idiopathic arthritis (JIA). METHODS The clinical charts of JIA patients followed over a 16-year period were reviewed to identify visits with high disease activity and MDA, defined on the basis of therapeutic decisions made by the attending physician. For each JIA activity measure recorded at the time of the visit, the cutoff value that best identified states of MDA was calculated by means of the area under the receiver operating characteristic curve analysis. A definition of MDA for oligoarthritis and polyarthritis was set up after testing the relative power of each variable in a multivariate analysis. Validation procedures included assessment of discriminant and construct validity. RESULTS The definition that resulted from the analyses led to establish that a state of MDA could be defined as the presence of a physician global assessment < or =2.5 cm and a swollen joint count of 0 in patients with oligoarthritis; and as the presence of a physician global assessment < or =3.4 cm, a parent global assessment < or =2.1 cm, and a swollen joint count < or =1 in patients with polyarthritis. Validation procedures demonstrated that the MDA definition had good discriminant and construct validity in the context of both observational studies and controlled trials. CONCLUSION We developed a preliminary definition of MDA in patients with JIA that represents a useful treatment target state and is proposed for inclusion as an outcome measure in future observational studies and clinical trials in patients with JIA.

Parent and child acceptable symptom state in juvenile idiopathic arthritis.

Objective. To explore the parent and child acceptable symptom state in juvenile arthritis (JA-PASS and JA-CASS, respectively) and estimate the JA-PASS and JA-CASS cutoff values for outcome measures. Methods. Children with juvenile idiopathic arthritis (JIA) and their parents completed a multi-dimensional questionnaire that included parent-reported and child-reported outcomes and a question about whether they considered the disease state as satisfactory. Additional assessments included demographic data, physician-reported outcomes, and acute-phase reactant levels. Stepwise logistic regression was used to assess contributors to JA-PASS and JA-CASS. Cutoff values of outcome measures that defined JA-PASS and JA-CASS were determined using both 75th percentile and receiver-operating characteristic (ROC) curve methods. Testing procedures included evaluation of discriminative and construct validity of the satisfaction question and assessment of reliability of JA-PASS and JA-PASS cutoffs. Results. Of 584 parents, 385 (65.9%) considered their child in JA-PASS. Of 343 children, 236 (68.8%) considered themselves in JA-CASS. Significant contributors to being in either JA-PASS or JA-CASS were absence of active joints, better rating of overall well-being, and better physical function or health. Cutoff values yielded by 75th percentile and ROC curve methods were similar. Parent, child, and physician global ratings yielded the lowest percentage of false-positive misclassification and the best tradeoff between sensitivity and specificity. The satisfaction question showed good discriminative and construct validity and the JA-PASS and JA-PASS cutoffs were found to be stable over time. Conclusion. The acceptable symptom state is a relevant concept for children with JIA and their parents and constitutes a valid outcome measure that is potentially applicable in routine practice and clinical trials.

Assessing current outcomes of juvenile idiopathic arthritis: A cross-sectional study in a tertiary center sample

OBJECTIVE To investigate the disease outcomes of a cross-sectional sample of children with longstanding juvenile idiopathic arthritis (JIA) seen between September 2002 and December 2006, and to provide a benchmarking of outcomes obtained with current treatment. METHODS All consecutive patients were included if they met the following criteria: diagnosis of JIA, disease duration > or = 5 years, and informed consent. Outcome assessments included disease activity, inactive disease, minimal disease activity, pain, physical function, health-related quality of life (HRQOL), auxometric measurements, and articular and extraarticular damage. RESULTS A total of 310 patients were included. At study visit, patients had on average a low level of disease activity. However, only 21.8% met the criteria for inactive disease, and less than 50% met the definition of minimal disease activity. Additionally, 19.2% had moderate to severe Childhood Health Assessment Questionnaire disability and 3.6% were in Steinbrocker class III-IV. Approximately 10% had major impairment in HRQOL. A total of 34.2% had damage in > or = 1 joint or joint group and 26.1% showed extraarticular damage. Of the 125 patients who underwent a wrist radiograph, 35.2% had significant structural damage and 8.7% had growth retardation. CONCLUSION Our patients had on average a low level of disease activity, little or no physical disability, and a satisfactory HRQOL. However, a sizable proportion of patients had persistently active disease, impaired function, and damage. These findings underscore the critical need for treatments and treatment strategies that have the ability to better control disease activity and to reduce the development of disease-related morbidities.

Factors Associated with Achievement of Inactive Disease in Children with Juvenile Idiopathic Arthritis Treated with Etanercept

Objective. To evaluate the rate of inactive disease in children with juvenile idiopathic arthritis (JIA) treated with etanercept, and to identify clinical characteristics associated with attainment of inactive disease. Methods. Clinical charts of patients who were given etanercept between January 2002 and January 2011 were evaluated retrospectively. For each patient, all visits from initiation of etanercept to the last followup evaluation in which the patient was still receiving etanercept were examined to establish whether the patient had reached the state of inactive disease and to identify the first visit in which inactive disease was documented. Clinical characteristics associated with achievement of inactive disease were determined through univariate analyses and Cox regression procedures. Results. A total of 173 patients who received etanercept for a median of 2.2 years (range 0.5–10.5 yrs) were studied. Eighty-seven patients (50.3%) achieved inactive disease after a median of 0.6 years (range 0.1–2.5 yrs) of therapy. At last followup evaluation, 85 patients (49.1%) still had inactive disease and 70 (40.5%) were in clinical remission on medication. The probability of achievement of inactive disease after 6, 12, and 24 months of therapy was 24%, 46% and 57%, respectively. On Cox regression analysis, the attainment of inactive disease was associated with lack of wrist involvement and an age at disease onset < 3.6 years. Conclusion. Around half of our patients with JIA treated with etanercept achieved a state of inactive disease. Children who lacked wrist involvement and were younger at disease onset had a greater likelihood of achieving inactive disease.

Development and initial validation of composite parent‐ and child‐centered disease assessment indices for juvenile idiopathic arthritis

To develop and validate a parent‐centered and a child‐centered composite disease assessment index for juvenile idiopathic arthritis (JIA): the Juvenile Arthritis Parent Assessment Index (JAPAI) and the Juvenile Arthritis Child Assessment Index (JACAI), respectively.

Agreement between physicians and parents in rating functional ability of children with juvenile idiopathic arthritis

ObjectiveTo investigate concordance between physicians and parents in rating the degree of functional ability of children with juvenile idiopathic arthritis (JIA).MethodsThe attending physician and a parent were asked to rate independently the level of physical functioning of 155 patients with disease duration ≥ 5 years on a 6-point scale ranging from 1 = no disability (i.e. the child can do without difficulty all activities that children of his/her age can do) to 6 = severe disability (i.e. all activities are difficult for the child). At study visit, measures of JIA activity and damage were assessed. Agreement was evaluated with weighted kappa (<0.40 = poor agreement; 0.41–0.60 = moderate agreement; 0.61–0.80 = substantial agreement; >0.80 excellent agreement). Physician/parent evaluations were divided in 3 groups: 1) concordance; 2) parent over-rating = parent assessment over-rated relative to physician assessment; 3) physician over-rating = physician assessment over-rated relative to parent assessment. Factors affecting concordance/discordance were evaluated by means of Kruskal-Wallis or Chi-square/Fisher exact test.ResultsConcordance, parent over-rating and physician over-rating were observed in 107 (69%), 29 (18.7%) and 19 (12.3%) evaluations, respectively. Kappa value was 0.69. Parent over-rating was associated with greater intensity of pain (p = 0.01) and higher Childhood Health Assessment Questionnaire (C-HAQ) score (p = 0.004), whereas physician over-rating was associated with more severe joint disease (p = 0.04 to <0.001), higher C-reactive protein (p = 0.03) higher frequency of Steinbrocker functional class = II (p < 0.001), and greater articular damage, as measured with the Juvenile Arthritis Damage Index (p < 0.001).ConclusionPhysicians and parents revealed fair concordance in rating functional ability of children with JIA. Parent over-rating was associated with greater childs pain and worse C-HAQ score, whereas physician over-rating was associated with greater severity of joint inflammation and damage.

Preliminary validation of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) in 403 clinic patients

Methods The JAMAR includes: Juvenile Arthritis Functionality Scale (JAFS) (0 = normal; 30 = worst), Pediatric Rheumatology Quality of Life (PRQL) questionnaire (0 = best; 30 = worst); visual analogue scales (0 = best; 10 = worst) for parent/patient rating of well-being (WB), pain (P), disease activity (DA); parent/patient assessment of morning stiffness, disease status, satisfaction about disease outcome.

Agreement between objective and subjective definitions of inactive disease, remission and minimal disease activity in juvenile idiopathic arthritis

Background In juvenile idiopathic arthritis (JIA), substantial disagreement between physicians, parents and children over disease remission can lead to difficulty in assessing the efficacy of treatments. It is, therefore, important to ascertain whether clinicians’, parents’ and children’s opinions converge and diverge and whether the recently developed criteria for inactive disease (ID) or minimal disease activity (MDA) may help enhance concordance. Objective

The diagnostic role of hyperferritinemia in a tertiary care pediatric rheumatology setting

Results More than 4000 determinations of ferritin requested by the study unit were performed between January 2004 and December 2007 by the central laboratory of the study hospital. Hyperferritinemia was found in 408 determinations in 87 patients. The most common specific diagnoses in patients with hyperferritinemia were the following: systemic juvenile idiopathic arthritis (sJIA) (48.3%), systemic lupus erythematosus (SLE) (5.7%), protein intolerance with lysinuria (4.6%), virus-associated haemophagocytic syndrome (3.4%), hematologic disorders (3.4%), juvenile dermatomyositis (2.3%), polyarticular JIA (2.3%), systemic vasculitis (2.3%), autoinflammatory syndrome (2.3%). Twelve patients (13.8%) had a nonspecific systemic inflammatory syndrome. Twenty-seven (31%) of the 87 patients with hyperferritinemia developed features consistent with MAS.