R. ten Cate

Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register

Objective: 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. Methods: 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. Results: 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). Conclusions: 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).

Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis

OBJECTIVE Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients. METHODS A cohort of 128 JIA patients treated with MTX were studied retrospectively. Eleven clinical parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related to the mechanism of action of MTX were compared between MTX responders and nonresponders using a multivariate regression analysis. RESULTS The time from diagnosis to start of MTX treatment, physicians global assessment at baseline, and the starting dose were significantly associated with the response to MTX at 6 months after initiation. Patients with a shorter time from diagnosis to start of MTX and a higher disease activity according to the physician but with a lower MTX dose showed an increased response. The effect of the starting dose on MTX response seemed to be mainly due to the influence of the systemic JIA subtype. The time from diagnosis to start of MTX treatment and physicians global assessment at baseline were highly correlated. Therefore, the precise effect size of each independent variable could not be determined. CONCLUSION In children with JIA, the time from diagnosis to start of MTX appears to be an important factor for MTX response. Our results suggest that an earlier start of MTX treatment will lead to an increased response.

Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis

Objective: To evaluate changes in health-related quality of life (HRQoL) in patients with refractory juvenile idiopathic arthritis (JIA) who are being treated with etanercept. Methods: 53 patients with JIA from seven Dutch centres were included. HRQoL was measured by the Childhood Health Assessment Questionnaire (CHAQ), Child Health Questionnaire (CHQ) and Health Utilities Index mark 3 (HUI3) at the start and after 3, 15 and 27 months of treatment. At the same time points the following JIA disease activity variables were collected; physician’s global assessment through the visual analogue scale (VAS), number of active and limited joints and erythrocyte sedimentation rate. A statistical method linear mixed models was used to assess outcomes over time. Results: During etanercept treatment both disease-specific and generic HRQoL outcomes improved dramatically. Significant improvements were shown after 3 months and these improvements continued at least up to 27 months of treatment. The disease-specific CHAQ, including VAS pain and wellbeing, showed a significant improvement in all domains. The generic health-profile measure CHQ improved for all the health concepts except for “family cohesion”, which was normal. The generic preference-based HUI3 showed impairment and, subsequently, significant improvement in the more specific domains (“pain”, “ambulatory”, “dexterity”). In accordance disease activity variables also improved significantly over time. Conclusion: This study shows that the HRQoL of patients with refractory JIA can be substantially improved by the use of etanercept for all aspects impaired by JIA. Information on HRQoL is crucial to understand the complete impact of etanercept treatment on patients with JIA and their families.

Long-term follow-up of autologous stem cell transplantation for refractory juvenile idiopathic arthritis

Summary:Since 1997, autologous stem cell transplantation (ASCT) had been applied to more than 40 children with polyarticular or systemic juvenile idiopathic arthritis (JIA). For this review, results of the follow-up are available from 25 children with systemic JIA and six with polyarticular JIA that were reported in detail from eight different pediatric European transplant centers. Before ASCT all children had progressive disease despite the use of corticosteroids, methotrexate (MTX) up to 1 mg/kg/week, cyclosporin (2.5 mg/kg/day) and/or anti-TNFα therapy. The clinical follow-up of these children ranges from 8 to 60 months (median 33 months).

Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years.

Development of a web-based register for the Dutch national study on biologicals in JIA: www.ABC-register.nl

OBJECTIVES Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study. METHODS We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data. RESULTS The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved. CONCLUSIONS By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

PReS-FINAL-2145: MRP8/14 serum complexes as predictor of response to etanercept treatment in juvenile idiopathic arthritis

Biological therapy has dramatically improved the treatment of patients with JIA. However, there is still a group of patients that shows a lack of clinical response to this treatment. The use of robust predictive markers of response to identify individuals who are likely to respond to etanercept may provide guidance in optimizing treatment strategies.

Does incorporation of aids/devices and help, make a difference in the childhood health assessment questionnaire disability index? Analysis from the printo juvenile idiopathic arthritis database

Open Access Poster presentation Does incorporation of aids/devices and help, make a difference in the childhood health assessment questionnaire disability index? Analysis from the printo juvenile idiopathic arthritis database C Saad-Magalhaes*, A Pistorio, A Ravelli, R Brik, D Mihaylova, R Ten Cate, B Andersson-Gare, V Ferriani, K Minden, P Hashkes, M Rygge, MJ Sauvain, H Venning, A Martini and Ruperto for the Paediatric Rheumatology International Trials Organisation (PRINTO) N

Development of a web-based register for the Dutch national study on biologicals in juvenile idiopathic arthritis: http://www.abc-register.nl

Address: 1Erasmus MC Sophia Childrens Hospital, Rotterdam, Netherlands, 2UMCG Beatrix Childrens Hospital, Groningen, Netherlands, 3Leiden University Medical Centre, Leiden, Netherlands, 4Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 5Hagaziekenhuis Juliana Childrens Hospital, Den Haag, Netherlands, 6AMC Emma Childrens Hospital, Amsterdam, Netherlands and 7Academic Hospital Maastricht, Maastricht, Netherlands * Corresponding author