Effects of Sulfasalazine Treatment in Juvenile Idiopathic Arthritis: Clinical and Radiological Observations

In Nederland heeft ongeveer één op de duizend kinderen jeugdreuma. De ziekte kenmerkt zich door chronische gewrichtsontstekingen die kunnen leiden tot blijvende gewrichtsschade. Onderzoeken naar de behandeling en de effecten hiervan op de lange termijn zijn beperkt. Het proefschrift van Marion van Rossum beschrijft een landelijk onderzoek naar de korte- en langetermijnuitkomst van kinderen met jeugdreuma die deelnamen aan een placebo gecontroleerde studie naar de werkzaamheid van het antireumaticum sulfasalazine. De resultaten van de studie laten zien dat sulfasalazine effectiever is dan een placebo in het onderdrukken van gewrichtsontstekingen en het vertragen van radiologisch zichtbare gewrichtsschade. Om de radiologische bevindingen te beschrijven werd een gestandaardiseerde radiologische scoringsmethode ontwikkeld. Deze is gevalideerd en geschikt voor studies bij kinderen met jeugdreuma. De studie naar de langetermijnuitkomst toont dat er nog veel te winnen valt in de behandeling van jeugdreuma. Bij een vervolgstudie die negen jaar na aanvang van de sulfasalazine-studie werd uitgevoerd, werd 90% van de oorspronkelijk deelnemers opnieuw onderzocht (leeftijd 18-25 jaar). 74% van de patiënten had nog steeds ontstoken gewrichten. Aanvullende analyses laten zien dat patiënten die op jonge leeftijd met sulfasalazine waren behandeld ook op latere leeftijd betere ziekte-uitkomstscores hadden dan de oorspronkelijke placebogroep. Bovendien maakten ze in de tussenliggende periode minder gewrichtsontstekingen door en hadden ze een minder intensieve anti-reumatische behandeling nodig. De vervolgstudie laat ook zien dat patiënten met een goede therapietrouw een betere ziekte-uitkomst op de lange termijn hebben. Deze bevindingen ondersteunen het belang van vroegtijdig starten van effectieve anti-reumatische behandeling en een goede therapietrouw bij jeugdreuma.Dijkmans, B.A.C. [Promotor]Boers, M. [Promotor]Soesbergen, R.M. van [Copromotor

Psychometric properties of the pediatric patient-reported outcomes measurement information system item banks in a Dutch clinical sample of children with juvenile idiopathic arthritis

Objective To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic arthritis (JIA).Methods A total of 154 Dutch children (mean +/- SD age 14.4 +/- 3.0 years; range 8-18 years) with JIA completed 8 pediatric version 1.0 PROMIS item banks (anger, anxiety, depressive symptoms, fatigue, pain interference, peer relationships, physical function mobility, physical function upper extremity) twice and the Pediatric Quality of Life Inventory (PedsQL) and the Childhood Health Assessment Questionnaire (C-HAQ) once. Structural validity of the item banks was assessed by fitting a graded response model (GRM) and inspecting GRM fit (comparative fit index [CFI], Tucker-Lewis index [TLI], and root mean square error of approximation [RMSEA]) and item fit (S-X-2 statistic). Convergent validity (with PedsQL/C-HAQ subdomains) and discriminative validity (active/inactive disease) were assessed. Reliability of the item banks, short forms, and computerized adaptive testing (CAT) was expressed as the SE of theta (SE[theta]). Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) and smallest detectable change.Results All item banks had sufficient overall GRM fit (CFI >0.95, TLI >0.95, RMSEA 0.001). High correlations (>0.70) were found between most PROMIS T scores and hypothesized PedsQL/C-HAQ (sub)domains. Mobility, pain interference, and upper extremity item banks were able to discriminate between patients with active and inactive disease. Regarding reliability, PROMIS item banks outperformed legacy instruments. Post hoc CAT simulations outperformed short forms. Test-retest reliability was strong (ICC >0.70) for all full-length item banks and short forms, except for the peer relationships item bank.Conclusion The pediatric PROMIS item banks displayed sufficient psychometric properties for Dutch children with JIA. PROMIS item banks are ready for use in clinical research and practice for children with JIA.Transplantation and immunomodulatio

Dutch–Flemish translation of nine pediatric item banks from the Patient-Reported Outcomes Measurement Information System (PROMIS)®

Purpose: The Patient-Reported Outcomes Measurement Information System (PROMIS®) is a new, state-of-the-art assessment system for measuring patient-reported health and well-being of adults and children. It has the potential to be more valid, reliable, and responsive than existing PROMs. The items banks are designed to be self-reported and completed by children aged 8–18 years. The PROMIS items can be administered in short forms or through computerized adaptive testing. This paper describes the translation and cultural adaption of nine PROMIS item banks (151 items) for children in Dutch–Flemish. Methods: The translation was performed by FACITtrans using standardized PROMIS methodology and approved by the PROMIS Statistical Center. The translation included four forward translations, two back-translations, three independent reviews (at least two Dutch, one Flemish), and pretesting in 24 children from the Netherlands and Flanders. Results: For some items, it was necessary to have separate translations for Dutch and Flemish: physical function—mobility (three items), anger (one item), pain interference (two items), and asthma impact (one item). Challenges faced in the translation process included scarcity or overabundance of possible translations, unclear item descriptions, constructs broader/smaller in the target language, difficulties in rank ordering items, differences in unit of measurement, irrelevant items, or differences in performance of activities. By addressing these challenges, acceptable translations were obtained for all items. Conclusion: The Dutch–Flemish PROMIS items are linguistically equivalent to the original USA version. Short forms are now available for use, and entire item banks are ready for cross-cultural validation in the Netherlands and Flanders

A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: Initial 3-months results of the BeSt for Kids-study

Background: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study. Methods: Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported. Results: 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported. Conclusion: After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy. Trial registration:NTR1574. Registered 3 December 2008

Selecting Magnetic Resonance Imaging (MRI) Outcome Measures for Juvenile Idiopathic Arthritis (JIA) Clinical Trials: First Report of the MRI in JIA Special Interest Group

Pathophysiology and treatment of rheumatic disease

Frequency of joint involvement in juvenile idiopathic arthritis during a 5-year follow-up of newly diagnosed patients: implications for MR imaging as outcome measure

Pathophysiology and treatment of rheumatic disease