juvenile idiopathic arthritis MedDRA version: 16.1 Level: LLT Classification code 10059177 Term: Juvenile arthritis System Organ Class: 100000004859
Conditions
Interventions
Trade Name: enbrel
Product Name: enbrel
Product Code: EU/1/99/126/001
Pharmaceutical Form: Injection
INN or Proposed INN: ETANERCEPT
CAS Number: 185243-69-0
Current Sponsor code: Pfizer Limited
Other
Sponsors
University Medical Center Utrecht
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with polyarticular course of any JIA subcategory (including extended oligoarthritis and polyarticular course of systemic JIA without systemic features) will be included at first confirmation of remission on medication, i.e. after clinically documented inactive disease (no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no active uveitis; no elevation in ESR or/and CRP attributable to JIA; physician’s global assessment of disease activity indicates no disease activity) for at least 6 months. Alternatively patients can be enrolled until 12 months (+/- 6 weeks) to ensure access to the study after 6 months of inactive disease. At the time remission is documented, patients may be ONLY on non-steroidal anti-inflammatory drugs (NSAIDs) plus DMARDs and/or biologics at a stable dose. Only approved medication is allowed during the study. Steroids must have been withdrawn at least 1 month before remission is documented. Intraarticular joint injections should not have been performed 6 months before remission is documented. At inclusion into this study patients will be considered being in clinically documented remission on medication. Are the trial subjects under 18? yes Number of subjects for this age range: 70 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients with persistent oligoarthritis subtype or systemic JIA having systemic features (within 1 year prior to inclusion) are excluded. In addition, patients may not have received treatment with steroids in the month before remission is first documented or treatment with intraarticular joint injections etc. in the 6 months before remission is first documented. Patient with a history of uveitis or macrophage activation syndrome are excluded. Patients may also not be included if withdrawal of any biological drug has ever been unsuccessful in the past.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - The main hypothesis of this study is that JIA patients at risk of a flare due to subclinical inflammatory activity may be identified by analysis of the phagocyte activity marker MRP8/14. The goal is a stratification of the therapeutic approach: Maintenance therapy for patients with elevated levels of the biomarker, stop of therapy if the biomarker is low.;Secondary Objective: - The second major hypothesis of this study is that a risk-stratified decision on withdrawal of therapy is superior to a random treatment stop time point (regarding the prevention of flares). - An additional hypothesis is that the current definition of remission may be refined, adding “immunological remission” as a status that will be robust enough to last after discontinuing medication. Other potentially useful markers, such as the granulocyte-activation markers S100A12 or hsCRP will be analyzed.;Primary end point(s): Patients in whom therapy is stopped will be compared with those who continue on maintenance therapy (=the two study groups). A comparison between these arms is mandatory as the main hypothesis is that withdrawal in a subgroup of patients with low risk of flares is safe, with flare rates not higher than in patients continuing medication. The stratification will be based upon S100A12/hsCRP levels measured in serum at each visit (i.e. every 3 months). After a watch and wait phase of 6 months in inactive disease, remission is confirmed according to the standard of care and patients will be stratified to stop therapy as soon as S100A12/hsCRP levels are below a specified threshold. As long as levels are above this threshold, patients will continue with maintenance therapy because a stable remission is not established. The stratification into these arms is dynamic.;Timepoint(s) of evaluation of this end point: after 30 months the individual has reached the end point | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The combined flare rate of all patients in the study will be compared to cohorts from previous studies providing robust data for a flare rate of 50% after random withdrawal of therapy shown independently in several studies. As it can be expected from our trial published in JAMA that the flare rate will be only around 25% with the stratified approach, we cannot withhold the chance of this superior approach from the patients included. The choice of comparisons was established in previous studies and for this purpose the BIKER-study will be used. The rationale for the biomarker to be tested, the units, and the cut off at 700 ng/ml was established in published work. Documentation is performed in intervals of 3 months in a prospective manner, starting with time point 0 month = first documentation of remission on medication. (alternatively 3 or 6 months). The documentation is planned using the PRINTO core set criteria, as well as draft criteria for definition of remission. 1) Patient data: Patient data will be collected as in CRFs 2) Patient history: Diagnosis, duration of disease, date of inclusion into the study, maximum of affected joints, maximal combined medication, time point of the discontinuation of DMARD/biological, time point of relapse (if applicable), date of examination 3) Joints: Joint with swelling, joints with limited motion, and joint pain. Joint with active arthritis is a joint with swelling not due to bony enlargement or, if no swelling is present, limitation of motion accompanied either by pain on motion and/or tenderness (16) 4) Core set criteria: a) MD global assessment (VAS scale 0-10cm); b) patient or parental assessment (VAS scale 0-10 cm); c) functional ability (CHAQ; grade 0-3 for 8 criteria; optionally CHAQ pain at defined time points); d) number of joints with active arthritis; e) number of joints with limited range of motion; f) erythrocyte sedimentation rate (ESR) 5) Criteria for clinical remission: a) No join | — |
Countries
Canada, Germany, Latvia, Netherlands, United States
Contacts
Public ContactBusiness Manager
University Medical Center Utrecht
Outcome results
None listed