Preliminary validation of clinical remission criteria using the OMERACT filter for select categories of juvenile idiopathic arthritis.
ABSTRACT To begin the validation process of the preliminary criteria for inactive disease (ID), clinical remission on medication (CRM), and clinical remission off medication (CR) in children with select forms of juvenile idiopathic arthritis (JIA).
We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter's 3 components: truth, discrimination, and feasibility, in 5 categories of JIA: systemic arthritis, persistent and extended oligoarthritis, and rheumatoid factor-positive and negative polyarthritis. Data sources for determining validity estimates included a Delphi questionnaire survey sent to 246 pediatric rheumatologists in 34 countries, a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries, a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years, and the literature.
Truth component: face and content validity. These aspects of validity were largely established via the Delphi questionnaire exercise and the consensus conference. Using an 80% consensus level, participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID, CRM, and CR. Criterion validity could not be irrefutably established because no gold standard for inactive disease exists for JIA. As an alternative, published investigations of remission in JIA were used to estimate concurrent and convergent validity, as surrogates for criterion validity and as indicators of overall construct validity. Correlational analyses revealed the new criteria to have good construct validity. Discrimination component: the criteria demonstrated moderate to high levels of classification, prognosis, and responsiveness (sensitivity to change) using data from the chart review. Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM. Responsiveness was evidenced by the ability of the criteria to allow movement of most patients between the disease states, consistent with what is known of the course of the disease. Feasibility component: Results of the Delphi and consensus conference produced a set of criteria that are easily, quickly, and inexpensively completed in the physician's office, and present minimal or no risk to the patient.
The preliminary criteria demonstrated moderate to excellent validity characteristics in some, but not all components of the OMERACT filter. Prospective validation studies are under way.
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ABSTRACT: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood, with many children requiring immunomodulatory therapies for many years following diagnosis. A considerable proportion of children experience therapeutic inefficacy or substantial adverse effects, or both, but a lack of reliable clinical indicators and biomarkers to predict treatment response prevents optimization of existing therapies. The identification of valid candidate gene variants involved in the pathways of methotrexate and etanercept, the most commonly used medications in JIA, has seen little success to date. The limited success of these studies is possibly due to the presence of confounding variables in the study populations, the heterogeneity of outcome parameters used to determine treatment response and the small number of candidate gene variants analysed. The first genome-wide pharmacogenetic study in JIA has identified gene regions of particular biological interest, but these findings require validation. Moreover, epigenetic mechanisms as well as ontogeny processes might be additional factors influencing drug responses. Access to large, well-documented JIA cohorts and the rapid development of advanced genome analytics is ushering in a personalized approach to treatment. The discovery of new pharmacogenomic biomarkers and systems pathways can provide new drug targets and predictive tools for improved drug response and fewer adverse drug reactions in JIA.Nature Reviews Rheumatology 08/2014; · 9.75 Impact Factor
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ABSTRACT: Objective Up to 90% of adults with rheumatoid arthritis (RA) in clinical remission have persistent synovitis and/or bone marrow lesions (BMLs) on magnetic resonance imaging (MRI). MRI findings in patients with juvenile idiopathic arthritis (JIA) in clinical remission have not been described. We utilized 3T MRI with contrast enhancement to examine JIA patients with hand and/or wrist involvement who were in clinical remission and compared them with a cohort of adult RA patients. Methods In total, 11 JIA patients and 10 RA patients with arthritis involving the hands and/or wrists were identified by their primary rheumatologist as being in physician-defined clinical remission, having no signs or symptoms of active arthritis and no medication changes for at least 6 months. A study rheumatologist performed a joint evaluation for tenderness, swelling, and limitation of motion, and study participants self-reported tender joint counts. The participants underwent MRI with intravenous contrast enhancement of 1 hand and wrist with a history of prior symptoms. A pediatric musculoskeletal radiologist blinded to the clinical data scored the MRIs for synovitis, tenosynovitis, and/or BMLs. ResultsSixty-three percent of the JIA cohort and 70% of the RA cohort had MRI findings of synovitis, BMLs, and/or tenosynovitis. All pediatric patients with MRI abnormalities had normal physician tender and swollen joint counts. The patients' self-report of painful joint counts did not predict MRI abnormalities. Conclusion Over one-half of the patients in clinical remission had MRI evidence of persistent inflammation, defined as the presence of synovitis, tenosynovitis, or BMLs. A substantial portion of patients with JIA may have subclinical disease despite clinical remission.Arthritis Care & Research. 12/2012; 64(12).
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ABSTRACT: To conduct a prospective cohort study using anakinra, a recombinant IL-1 receptor antagonist (IL-1Ra), as first-line therapy in patients with new-onset systemic juvenile idiopathic arthritis (JIA). Therapy with recombinant IL-1Ra (2 mg/kg) was initiated in 20 patients who fulfilled the International League of Associations for Rheumatology criteria for systemic JIA, before systemic steroid treatment was administered. Patients were monitored clinically and immunologically. The protocol contained a stop strategy for patients who met at least the adapted American College of Rheumatology 90% criteria for improvement in JIA (ACR Pediatric 90 [ACR Pedi 90]) after 3 months. We included consecutive patients with new-onset systemic JIA. The mean followup period was 32 months (range 12-54 months). At the 3-month time point, 85% of the patients showed an adapted ACR Pedi 90 response or had inactive disease; 75% of the patients achieved this response while receiving recombinant IL-1Ra alone. After 1 year, 17 of the 20 patients met the criteria for clinically inactive disease, and 13 of these patients met these criteria while receiving monotherapy with recombinant IL-1Ra. However, because of persistent disease activity, 7 of the 20 patients required additional therapy besides recombinant IL-1Ra. According to our stop strategy, 73% of patients with at least an adapted ACR Pedi 90 response at 3 months could stop recombinant IL-1Ra treatment within 1 year. After 2 years, 12 (86%) of 14 patients met the criteria for disease remission, either while receiving (n = 4) or not receiving (n = 8) medication. After 3 years, 10 (91%) of 11 patients met the criteria for disease remission, either while receiving (n = 2) or not receiving (n = 8) medication. This is the first prospective study in which recombinant IL-1Ra was used as first-line therapy in patients with systemic JIA. We observed excellent responses in nearly all patients within 3 months. In the majority of responding patients, treatment with recombinant IL-1Ra could be stopped within 1 year, with remission being preserved during followup. In approximately one-third of patients, concomitant therapy was required for maintenance of clinical response.Arthritis & rheumatology (Hoboken, N.J.). 04/2014; 66(4):1034-43.