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Janneke Anink,
Marieke H Otten,
Simone L Gorter,
Femke H M Prince,
Marion A J van Rossum,
J Merlijn van den Berg,
Philomine A van Pelt,
Sylvia Kamphuis,
Danielle M C Brinkman,
Wijnand A A Swen,
Joost F Swart,
Nico M Wulffraat,
Koert M Dolman,
Yvonne Koopman-Keemink,
Esther P A H Hoppenreijs, Wineke Armbrust,
Rebecca Ten Cate,
Lisette W A van Suijlekom-Smit
[show abstract]
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ABSTRACT: Objectives. To evaluate differences in baseline characteristics between etanercept- and adalimumab-treated JIA patients and to reveal factors that influence the choice between these TNF inhibitors, which are considered equally effective in the recent ACR recommendations for JIA treatment.Methods. Biologic-naïve JIA patients with active arthritis who started treatment with adalimumab or etanercept between March 2008 and December 2011 were selected from the Dutch Arthritis and Biologicals in Children register. Baseline characteristics were compared. Focus group interviews with paediatric rheumatologists were performed to evaluate factors determining treatment choices.Results. A total of 193 patients started treatment with etanercept and 21 with adalimumab. Adalimumab-treated patients had longer disease duration prior to the start of biologics (median 5.7 vs 2.0 years) and more often a history of uveitis (71% vs 4%). Etanercept-treated patients had more disability at baseline (median Childhood Health Assessment Questionnaire score 1.1 vs 0.4) and more active arthritis (median number of active joints 6 vs 4). The presence of uveitis was the most important factor directing the choice towards adalimumab. Factors specific for the paediatric population-such as painful adalimumab injections-as well as the physician's familiarity with the drug accounted for the preference for etanercept.Conclusion. Although the two TNF inhibitors are considered equally effective, in daily practice etanercept is most often prescribed; adalimumab is mainly preferred when uveitis is present. In choosing the most suitable biologic treatment, paediatric rheumatologists take into account drug and patient factors, considering newly published data and cautiously implementing this into daily care.
Rheumatology (Oxford, England) 06/2013; · 4.24 Impact Factor
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Janneke Anink,
Marieke H Otten,
Femke H M Prince,
Esther P A H Hoppenreijs,
Nico M Wulffraat,
Joost F Swart,
Rebecca Ten Cate,
Marion A J van Rossum,
J Merlijn van den Berg,
Koert M Dolman,
Yvonne Koopman-Keemink, Wineke Armbrust,
Sylvia Kamphuis,
Philomine A van Pelt,
Simone L Gorter,
Lisette W A van Suijlekom-Smit
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ABSTRACT: Objective. Because TNF inhibitors are not approved for persistent oligoarticular JIA (oJIA), although they are used off-label, we evaluated their effectiveness in patients in this category.Methods. Persistent oJIA patients were selected from the Dutch Arthritis and Biologicals in Children (ABC) register, an ongoing multicentre prospective study that aims to include all Dutch children with JIA using biologic agents. Response was assessed by the JIA core-set disease activity variables and modified Wallace criteria for inactive disease.Results. Until February 2011, 16 persistent oJIA patients (68.8% females) had been included in the register. Median age of onset was 8.4 years [interquartile range (IQR) 2.1-13.5 years]; history of uveitis in 18.8%; ANA-positive 56.3%. All had previously used MTX, and 81.3% had used IA CSs. Median follow-up after the introduction of biologic treatment was 13.7 months (IQR 8.3-16.7 months). Fourteen patients started etanercept and two patients who had active arthritis as well as uveitis started adalimumab. Although patients with persistent oJIA had few affected joints [median of two active joints at the start of biologic (IQR 1-3)], the patient/parent assessments of pain [median visual analogue score (VAS) 51 (IQR 1-64)] and well-being [median VAS 44 (IQR 6-66)] were high. Additionally, their physician evaluated the disease activity as moderately high [median VAS 36 (IQR 4-65)]. After 3 months this decreased to 0 (IQR 0-30) and 63% achieved inactive disease. After 15 months the disease was inactive in 9/10 observed patients. TNF inhibitors were tolerated well.Conclusion. TNF blocking agents seem an effective and justifiable option in persistent oJIA when treatment with IA CS injections and MTX has failed.
Rheumatology (Oxford, England) 12/2012; · 4.24 Impact Factor
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Marieke H Otten,
Femke H M Prince,
Janneke Anink,
Rebecca Ten Cate,
Esther P A H Hoppenreijs, Wineke Armbrust,
Yvonne Koopman-Keemink,
Philomine A van Pelt,
Sylvia Kamphuis,
Simone L Gorter,
Koert M Dolman,
Joost F Swart,
J Merlijn van den Berg,
Nico M Wulffraat,
Marion A J van Rossum,
Lisette W A van Suijlekom-Smit
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ABSTRACT: OBJECTIVE: To evaluate the effectiveness and safety of switching to a second or third biological agent in juvenile idiopathic arthritis (JIA) after etanercept failure. METHODS: The Arthritis and Biologicals in Children Register aims to include all Dutch JIA patients who have used biological agents. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates. RESULTS: Of 307 biologically naive JIA patients who started etanercept, 80 (26%) switched to a second and 22 (7%) to a third biological agent. During 1030 patient-years of follow-up after the introduction of etanercept, 49 switches to adalimumab, 28 infliximab, 17 anakinra, four abatacept and four trial drugs were evaluated. 84% (95% CI 80% to 88%) of patients who started etanercept as a first biological agent were, after 12 months, still on the drug, compared with 47% (95% CI 35% to 60%) who started a second and 51% (95% CI 26% to 76%) who started a third biological agent. Patients who switched because of primary ineffectiveness continued the second agent less often (32%, 95% CI 12% to 53%). After etanercept failure, drug continuation of adalimumab was similar to infliximab for patients with non-systemic JIA; anakinra was superior to a second TNF-blocker for systemic JIA. AE rates within first 12 months after initiation were comparable for each course and each biological agent. CONCLUSIONS: Switching to another biological agent is common, especially for systemic JIA patients. A second (and third) agent was less effective than the first. The choice of second biological agent by the physician mainly depends on availability and JIA category.
Annals of the rheumatic diseases 06/2012; · 8.11 Impact Factor
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Marieke H Otten,
Femke H M Prince, Wineke Armbrust,
Rebecca ten Cate,
Esther P A H Hoppenreijs,
Marinka Twilt,
Yvonne Koopman-Keemink,
Simone L Gorter,
Koert M Dolman,
Joost F Swart,
J Merlijn van den Berg,
Nico M Wulffraat,
Marion A J van Rossum,
Lisette W A van Suijlekom-Smit
[show abstract]
[hide abstract]
ABSTRACT: Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal.
To determine the response to therapy after initiation of etanercept therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment.
The Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, includes all Dutch JIA patients who used biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years.
Excellent response (inactive disease or discontinuation earlier due to disease remission), intermediate response (more than 50% improvement from baseline, but no inactive disease), and poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance) evaluated 15 months after initiation of etanercept.
At 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; adjusted odds ratio [OR] per point increase, 0.49; 95% CI, 0.33-0.74); fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43-0.95), and younger age at onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99). Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92; 95% CI, 1.26-6.80), and female sex (adjusted OR female vs male, 2.16; 95% CI, 1.12-4.18). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months (95% CI, 46.4-52.0) for patients with an excellent response after 15 months, 47.5 months (95% CI, 44.9-50.1) for patients with an intermediate response, and 17.4 months (95% CI, 13.6-21.2) for patients with a poor response.
Among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female sex.
JAMA The Journal of the American Medical Association 11/2011; 306(21):2340-7. · 30.03 Impact Factor
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Marieke H Otten,
Femke H M Prince,
Marinka Twilt,
Rebecca Ten Cate, Wineke Armbrust,
Esther P A H Hoppenreijs,
Yvonne Koopman-Keemink,
Nico M Wulffraat,
Simone L Gorter,
Koert M Dolman,
Joost F Swart,
J Merlijn van den Berg,
Marion A J van Rossum,
Lisette W A van Suijlekom-Smit
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the effectiveness and safety of biological agents in children with enthesitis-related arthritis (ERA).
All patients with ERA in whom a biological agent was initiated between 1999 and 2010 were selected from the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing multicenter observational register, data on the course of the disease and medication use are retrieved prospectively at the start of the biological agent, after 3 months, and yearly thereafter. Inactive disease was assessed in accordance with the Wallace criteria.
Twenty-two patients with ERA started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched from etanercept to infliximab). Characteristics: 77% were male, 77% had enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4-12.0) years; median followup from the start of the biological agent was 1.2 (IQR 0.5-2.4) years. Intention-to-treat analysis shows that inactive disease was achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after 15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients discontinued etanercept because of ineffectiveness, and switched to adalimumab (inactive disease achieved) or infliximab (decline in joints with arthritis after 3 months of treatment). One patient discontinued etanercept because of remission, but had flare and restarted treatment, with good clinical response. No serious adverse events occurred.
Tumor necrosis factor (TNF)-blocking agents seem effective and safe for patients with ERA that was previously unresponsive to 1 or more DMARD. However, a sustained disease-free state could not be achieved, and none discontinued TNF-blocking agents successfully.
The Journal of Rheumatology 08/2011; 38(10):2258-63. · 3.69 Impact Factor
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ABSTRACT: In Rheumatoid Arthritis (RA) and Juvenile Idiopathic Arthritis (JIA) elimination of autoreactive T-cells by FasL/Fas-mediated Activation-Induced Cell Death (AICD) appears to be inhibited resulting in the perpetuation of the inflammatory response and concomitant progressive tissue destruction. Here, we report on a novel strategy that aims to overcome the local inhibition of AICD by using rationally designed recombinant fusion proteins in which sFasL is genetically fused to a T-cell selective targeting domain. The series included sFasL fusion proteins with engineered binding specificity for various T-cell surface-expressed proteins including CD7, CD28, RANKL and CD40L. The proposed mode of action is that selective binding of a given sFasL fusion protein results in its accretion at the cell surface of T-cells only, displaying a surplus of sFasL that is available to reactivate AICD in pathogenic synovial T-cells. Of the series of T-cell targeting FasL fusion proteins a CD7-targeted fusion protein, designated scFvCD7:sFasL, proved to be the most potent, with significant pro-apoptotic activity towards synovial fluid T-cells in all patient samples tested (RA; n=22: JIA; n=6). Treatment with scFvCD7:sFasL induced up to 80% apoptosis in CD3-positive synovial T-cells. Importantly, scFvCD7:sFasL potently activated Fas-signaling in synovial T(H1)-cells as well as synovial T(reg) cells, but not in synovial T(H2) cells. These findings indicate that scFvCD7:sFasL may be of therapeutic value for the selective elimination of pathogenic synovial T-cells of the T(H1) subtype in both RA and JIA.
Immunology letters 04/2011; 138(2):161-8. · 2.91 Impact Factor
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Trudy D van Dijken,
Sebastiaan J Vastert,
Valeria M Gerloni,
Irene Pontikaki,
Kristina Linnemann,
Hermann Girschick, Wineke Armbrust,
Kirsten Minden,
Femke H M Prince,
Freddy T M Kokke,
Edward E S Nieuwenhuis,
Gerd Horneff,
Nico M Wulffraat
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ABSTRACT: With the increasing use of etanercept for juvenile idiopathic arthritis (JIA) new possible adverse events are reported including new autoimmune diseases. Our purpose was to examine if the incidence of inflammatory bowel disease (IBD) in patients with JIA using etanercept is higher than in the healthy age-matched population. We give the clinical characteristics of the IBD in patients with JIA using etanercept.
The national JIA registries for etanercept of The Netherlands, Germany, Finland, Denmark, and Italy were searched for patients with JIA and IBD. The total number of patient-years was used to calculate incidence. The physicians of the identified patients were asked to give clinical details.
Thirteen cases of IBD in JIA patients were identified in the registries between 1999 and 2008. The IBD incidence in JIA patients while using etanercept was 362 per 100,000 patient-years under etanercept, about 43 times higher than in the general pediatric population. Clinical presentation of IBD in JIA patients using etanercept was similar to that in non-JIA patients. The median time between onset of JIA and onset of IBD was 6 years and 10 months. The time between the start of etanercept and the first appearance of IBD symptoms was between 9 days and 4.5 years.
The incidence of IBD in JIA patients using etanercept seems to be markedly increased, analyzing data from European registries. This incidence of IBD in the etanercept registries cannot be compared to the incidence of IBD in JIA patients using other treatment without etanercept, because such registries do not exist yet in all European countries. These findings are in keeping with a report of 8 new IBD cases occurring in French children with JIA using etanercept. These findings illustrate the need for large international disease-specific registries focused on outcome and pharmacovigilance.
The Journal of Rheumatology 04/2011; 38(7):1441-6. · 3.69 Impact Factor
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Maja Bulatović,
Marloes W Heijstek,
Marleen Verkaaik,
E H Pieter van Dijkhuizen, Wineke Armbrust,
Esther P A Hoppenreijs,
Sylvia Kamphuis,
Wietse Kuis,
Toine C G Egberts,
Gerben Sinnema,
Carin M A Rademaker,
Nico M Wulffraat
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ABSTRACT: To design and validate a new questionnaire for identifying patients with methotrexate (MTX) intolerance, and to determine the prevalence of MTX intolerance in patients with juvenile idiopathic arthritis (JIA) using this questionnaire.
The MTX Intolerance Severity Score (MISS) questionnaire was constructed, consisting of 5 domains: stomach ache, nausea, vomiting, sore mouth, and behavioral symptoms. The domains each consisted of 3 questions pertaining to the presence of a symptom upon, prior to (anticipatory), and when thinking of (associative) MTX intake. The MISS questionnaire was validated in 86 patients by determining its discriminative power between patients with and those without MTX intolerance, identified as such by a gold standard (physician's opinion). Using the MISS questionnaire, the prevalence of MTX intolerance was determined in 297 JIA patients.
The MISS questionnaire discriminated well between MTX-intolerant and MTX-tolerant patients. A cutoff score of 6 yielded the best sensitivity (88%) and specificity (80%). MTX intolerance was found in 150 (50.5%) of 297 patients. Of 220 patients receiving oral MTX, 98 (44.5%) experienced MTX intolerance, whereas 67.5% of 77 patients receiving parenteral MTX experienced intolerance to the drug (P = 0.001).
Our findings indicate that the MISS questionnaire is a highly sensitive and specific tool for the diagnosis of MTX intolerance, and that there is a high prevalence of MTX intolerance among JIA patients. The prevalence of intolerance in patients receiving parenteral MTX exceeds that in patients receiving oral MTX. The frequent occurrence of anticipatory and associative symptoms suggests that classic conditioning plays an important role in MTX intolerance.
Arthritis & Rheumatism 03/2011; 63(7):2007-13. · 7.87 Impact Factor
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Marieke H Otten,
Femke H M Prince,
Rebecca Ten Cate,
Marion A J van Rossum,
Marinka Twilt,
Esther P A H Hoppenreijs,
Yvonne Koopman-Keemink,
Arnold P Oranje,
Flora B de Waard-van der Spek,
Simone L Gorter, Wineke Armbrust,
Koert M Dolman,
Nico M Wulffraat,
Lisette W A van Suijlekom-Smit
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ABSTRACT: To evaluate the effectiveness of tumour necrosis factor (TNF) blockers in juvenile psoriatic arthritis (JPsA).
The study was a prospective ongoing multicentre, observational study of all Dutch juvenile idiopathic arthritis (JIA) patients using biologicals. The response of arthritis was assessed by American College of Rheumatology (ACR) paediatric response and Wallace inactive disease criteria. The response of psoriatic skin lesions was scored by a 5-point scale.
Eighteen JPsA patients (72% female, median age onset 11.1 (range 3.3-14.6) years, 50% psoriatic skin lesions, 39% nail pitting, 22% dactylitis) were studied. The median follow-up time since starting anti-TNFα was 26 (range 3-62) months. Seventeen patients started on etanercept and one started on adalimumab. After 3 months of treatment 83% of the patients achieved ACR30 response, increasing to 100% after 15 months. Inactive disease reached in 67% after 39 months. There was no discontinuation because of inefficacy. Six patients discontinued treatment after a good clinical response. However, five patients flared and restarted treatment, all with a good response. During treatment four patients (two JPsA and two JIA patients with other subtypes) developed de novo psoriasis. In four of the nine patients the pre-existing psoriatic skin lesions improved.
Anti-TNFα therapy in JPsA seems effective in treating arthritis. However, in most patients the arthritis flared up after treatment discontinuation, emphasising the need to investigate optimal therapy duration. The psoriatic skin lesions did not respond well and four patients developed de novo psoriasis.
Annals of the rheumatic diseases 11/2010; 70(2):337-40. · 8.11 Impact Factor
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Dirk Foell,
Nico Wulffraat,
Lucy R Wedderburn,
Helmut Wittkowski,
Michael Frosch,
Joachim Gerss,
Valda Stanevicha,
Dimitrina Mihaylova,
Virginia Ferriani,
Florence Kanakoudi Tsakalidou, [......],
María Luz Gamir,
Julia García-Consuegra,
Loredana Lepore,
Gordana Susic,
Fabrizia Corona,
Pavla Dolezalova,
Angela Pistorio,
Alberto Martini,
Nicolino Ruperto,
Johannes Roth
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ABSTRACT: Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions.
To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares.
Prospective, open, multicenter, medication-withdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined.
Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after induction of disease remission.
Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed.
Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P = .86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P = .61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1 110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P = .003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90).
In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate.
isrctn.org Identifier: ISRCTN18186313.
JAMA The Journal of the American Medical Association 04/2010; 303(13):1266-73. · 30.03 Impact Factor
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Marieke H Otten,
Femke H M Prince,
Marinka Twilt,
Marion A J van Rossum, Wineke Armbrust,
Esther P A H Hoppenreijs,
Sylvia Kamphuis,
Yvonne Koopman-Keemink,
Nico M Wulffraat,
Simone L Gorter,
Rebecca Ten Cate,
Lisette W A van Suijlekom-Smit
[show abstract]
[hide abstract]
ABSTRACT: To evaluate response in patients with juvenile idiopathic arthritis (JIA) who failed to meet response criteria after 3 months of etanercept treatment.
This was a prospective ongoing multicenter observational study of all Dutch patients with JIA using etanercept. Response according to American College of Rheumatology Pediatric 30 criteria was assessed at study start and at 3 and 15 months.
In total we studied 179 patients of median age 5.8 years at disease onset; 70% were female. Thirty-four patients did not respond after 3 months, of which 20 continued etanercept and 11 achieved response thereafter.
The delayed clinically relevant response in a substantial proportion of patients who initially did not respond justifies the consideration of continuing therapy to at least 6 months.
The Journal of Rheumatology 03/2010; 37(3):665-7. · 3.69 Impact Factor
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ABSTRACT: Patients with juvenile idiopathic arthritis (JIA) are less physically active than healthy peers. Therefore, we developed an Internet-based intervention to improve physical activity (PA). The aim of this study was to examine the effectiveness of the program in improving PA.
PA was determined by activity-related energy expenditure, PA level, time spent on moderate to vigorous PA, and the number of days with > or =1 hour of moderate to vigorous activity, and was assessed with a 7-day activity diary. Aerobic exercise capacity was assessed by means of a Bruce treadmill test and was recorded as maximum endurance time. Disease activity was assessed by using the JIA core set. Adherence was electronically monitored.
Of 59 patients, 33 eligible patients were included and randomized in an intervention (n = 17, mean +/- SD age 10.6 +/- 1.5 years) or control waiting-list group (n = 16, mean +/- SD age 10.8 +/- 1.4 years). All patients completed baseline and T1 testing. PA significantly improved in both groups. Maximum endurance time significantly improved in the intervention group but not in the control group. In a subgroup analysis for patients with low PA (intervention: n = 7, control: n = 5), PA improved in the intervention group but not in the control group. The intervention was safe, feasible, and showed a good adherence.
An Internet-based program for children with JIA ages 8-12 years directed at promoting PA in daily life effectively improves PA in those patients with low PA levels. It is also able to improve endurance and it is safe, feasible, and has good adherence.
Arthritis care & research. 01/2010; 62(5):697-703.
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ABSTRACT: To explore physical activity (PA) in adolescents with juvenile idiopathic arthritis (JIA) compared with a healthy population and to examine associations between PA and disease-related factors.
Total energy expenditure (TEE), activity-related energy expenditure (AEE), PA level, and PA pattern were assessed with a 3-day activity diary. Aerobic capacity was assessed using a Symptom Limited Bicycle Ergometry test. Functional ability was assessed with the Childhood Health Assessment Questionnaire. Disease activity was assessed using Paediatric Rheumatology International Trials Organisation core set criteria. Overall well-being was measured using a visual analog scale, and time since diagnosis was assessed by retrospective study from patients' charts. We used a cross-sectional study design. Reference data were collected from healthy Dutch secondary school children.
Thirty patients and 106 controls were included (mean+/-SD age 17.0+/-0.6 and 16.7+/-0.9 years, respectively). TEE, AEE, and PA level were significantly lower in the JIA group. The JIA group spent more time in bed and less time on moderate to vigorous PA. Only 23% of the JIA patients met public health recommendations to perform >or=1 hour daily moderate to vigorous PA compared with 66% in the reference group. Higher PA was associated with higher levels of well-being and maximal oxygen consumption.
Adolescents with JIA have low PA levels and are at risk of losing the benefits of PA. Low PA is not related to disease activity, and control over the disease does not restore previous PA levels. Interventions by pediatric rheumatologists are needed to increase PA levels in patients with JIA.
Arthritis & Rheumatism 11/2008; 59(10):1379-84. · 7.87 Impact Factor
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ABSTRACT: 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.
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.
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).
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).
Annals of the rheumatic diseases 05/2008; 68(5):635-41. · 8.11 Impact Factor
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ABSTRACT: To assess the effect of measles, mumps and rubella (MMR) vaccination on disease activity in children with juvenile idiopathic arthritis (JIA).
A retrospective observational multicentre cohort study was performed in 314 patients with JIA, born between 1989 and 1996. Disease activity and medication use were compared during the period of 6 months before vaccination versus 6 months after vaccination. Disease activity was measured by joint counts, the Physician's global assessment scale and erythrocyte sedimentation rate. Next, we compared disease activity in patients vaccinated between 8 and 9 years of age with the activity in patients who had not been vaccinated at this time (who received MMR between the ages of 9 and 10 years).
No increase in disease activity or medication use was seen in the 6 months after MMR vaccination (n = 207), including in patients using methotrexate (n = 49). No overt measles infections were noted. When disease activity in vaccinated patients (n = 108) was compared with activity in those not yet vaccinated (n = 86), there were no significant differences.
The MMR booster vaccination does not seem to aggravate disease activity in JIA. This indicates that the most patients with JIA can be vaccinated safely with the MMR vaccine. A prospective study is recommended.
Annals of the Rheumatic Diseases 11/2007; 66(10):1384-7. · 8.73 Impact Factor
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ABSTRACT: To examine the aerobic and anaerobic exercise capacity in adolescents with juvenile idiopathic arthritis (JIA) compared with age- and sex-matched healthy individuals, and to assess associations between disease-related variables and aerobic and anaerobic exercise capacity.
Of 25 patients enrolled in a JIA transition outpatient clinic, 22 patients with JIA were included in this study (mean +/- SD age 17.1 +/- 0.7 years, range 16-18 years). Aerobic capacity was examined using a Symptom Limited Bicycle Ergometry test. Anaerobic capacity was assessed with the Wingate Anaerobic Test. Functional ability was assessed with the Childhood Health Assessment Questionnaire. Pain and overall well-being were measured using a visual analog scale. Disease duration and disease activity were also assessed.
Absolute and relative maximal oxygen consumption in the JIA group were significantly impaired (85% and 83% for boys, respectively; 81% and 78% for girls, respectively) compared with healthy controls. Mean power was also significantly impaired (88% for boys and 74% for girls), whereas peak power was significantly impaired for girls and just failed significance for boys (67% for girls and 92% for boys). A post hoc analysis correcting for underweight and overweight demonstrated that body composition did not influence the results substantially.
This study demonstrated that adolescents with JIA have an impaired aerobic and anaerobic exercise capacity compared with healthy age- and sex-matched peers. The likely cause for this significant impairment is multifactorial and needs to be revealed to improve treatment strategies.
Arthritis & Rheumatism 09/2007; 57(6):898-904. · 7.87 Impact Factor
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ABSTRACT: Promoting Physical Activity in Children With Juvenile Idiopathic Arthritis Through an Internet-Based Program: Results of a Pilot Randomized Controlled Trial OTTO T. H. M. LELIEVELD,1 WINEKE ARMBRUST,2 JAN H. B. GEERTZEN,3 INEZ DE GRAAF,2 MIEK A. VAN LEEUWEN,1 PIETER J. J. SAUER,2 ELLEN VAN WEERT,3 AND JELTE BOUMA4 Objective. Patients with juvenile idiopathic arthritis (JIA) are less physically active than healthy peers. Therefore, we developed an Internet-based intervention to improve physical activity (PA). The aim of this study was to examine the effectiveness of the program in improving PA. Methods. PA was determined by activity-related energy expenditure, PA level, time spent on moderate to vigorous PA, and the number of days with >1 hour of moderate to vigorous activity, and was assessed with a 7-day activity diary. Aerobic exercise capacity was assessed by means of a Bruce treadmill test and was recorded as maximum endurance time. Disease activity was assessed by using the JIA core set. Adherence was electronically monitored. Results. Of 59 patients, 33 eligible patients were included and randomized in an intervention (n _ 17, mean _ SD age 10.6 _ 1.5 years) or control waiting-list group (n _ 16, mean _ SD age 10.8 _ 1.4 years). All patients completed baseline and T1 testing. PA significantly improved in both groups. Maximum endurance time significantly improved in the intervention group but not in the control group. In a subgroup analysis for patients with low PA (intervention: n _ 7, control: n _ 5), PA improved in the intervention group but not in the control group. The intervention was safe, feasible, and showed a good adherence. Conclusion. An Internet-based program for children with JIA ages 8–12 years directed at promoting PA in daily life effectively improves PA in those patients with low PA levels. It is also able to improve endurance and it is safe, feasible, and has good adherence. INTRODUCTION Children and adolescents with juvenile idiopathic arthritis (JIA) have reduced aerobic and anaerobic exercise capacity (1–3). There is also evidence that they are less physically active as compared with healthy peers (4,5). As a result, they may perceive difficulties in joining regular sport activities and in social interaction. It is unclear if this is the cause of the low exercise capacity or the result of it. Physical activity (PA) and physical fitness are interrelated (6). PA can be described as all leisure and non-leisure body movements resulting in an increased energy output from the resting condition (7). To become and remain physically fit, it is necessary to become physically active and to adopt and maintain a physically active lifestyle (8). Evidence is accumulating that PA is effective in the primary and secondary prevention of several chronic conditions (9 –11). PA is also associated with a reduction in all-cause mortality (11). There is evidence that in youth ages 6–16 years, PA controls body weight; reduces blood pressure in hypertensive youth; improves aerobic capacity, muscular strength, endurance, and skeletal health; reduces anxiety and depression; and improves self-concept (12). PA also has a positive effect on academic performance, concentration, memory, and classroom behavior (12). For children with JIA and other chronic diseases, it is recognized that they could take advantage of the same health benefits (13,14). Evidence supports the fact that PA . 1Otto T. H. M. Lelieveld, BSc, Miek A. van Leeuwen, MD, PhD: University Medical Center Groningen, Groningen, The Netherlands; 2Wineke Armbrust, MSc, Inez de Graaf, BSc, Pieter J. J. Sauer, PhD: Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, The Netherlands; 3Jan H. B. Geertzen, MD, PhD, Ellen van Weert, PhD: University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; 4Jelte Bouma, PhD: University of Groningen, Groningen, The Netherlands. Address correspondence to Otto T. H. M. Lelieveld, BSc, Center for Rehabilitation, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. E-mail: o.t.h.m.lelieveld@rev.umcg.nl. Submitted for publication September 28, 2009; accepted in revised form January 6, 2010. Arthritis Care & Research Vol. 62, No. 5, May 2010, pp 697–703 DOI 10.1002/acr.20085 © 2010, American College of Rheumatology ORIGINAL ARTICLE 697
