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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000312-15 | EudraCT Number |
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| Name | Class |
|---|---|
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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As biologic treatments are expensive and associated with some concerns regarding long-term safety, investigator hypothesize that early tapering and then withdrawal of biological agent, in an homogenous group of children with juvenile idiopathic arthritis achieving inactive disease, is safe and not inferior to the maintenance of stable treatment intensity over 24 weeks. In addition, investigator also hypothesize that an earlier tapering of treatment is associated with a better quality-of-life and a general cost saving effect. MRP8/14 will be studied as a potential biomarker for the risk of relapse. A study for biologic agent, anti-biologic agent antibodies and a pharmacogenomic approach will complete the research, as pharmacokinetic study during withdrawal of biologic treatment are rare in children.
Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis of unknown etiology starting before the age of 16. There are four to five thousand paediatric patients with JIA in France. Most of these patients are diagnosed with oligoarticular or rheumatoid factor negative polyarticular JIA. The prognosis of the disease has dramatically improved thanks to the introduction of biologic agents in patients with an extended oligoarticular or rheumatoid factor negative polyarticular JIA and inadequate response to methotrexate. Inactive disease and long-lasting clinical remission are achieved in most cases. "Treat to target" approaches are increasingly recommended, with earlier introduction of biologics, however the way to taper or withdraw treatment in patients achieving inactive disease is not codified. As biologic treatments are expensive and associated with some concerns regarding long-term safety, this study aim to test, in a randomized fashion, the hypothesis that early tapering of biologic agents (i.e. increasing the intervals between injections as soon as inactive disease is documented) is safe and non-inferior to the maintenance of stable treatment intensity over 24 weeks, and therefore test the possibility of early biologic agent withdrawal. It will also study concentrations of different biological agent, the occurrence of anti-drugs antibodies while tapering and then withdrawing biologics, and their possible association with a higher risk of relapse. In addition, investigators will test if the serum level of proteins 100 (MRP8/14) could be predictive of flares. Finally, pharmaco-economic analyses and quality of life studies will be conducted.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental | Experimental |
|
|
| Control | Active Comparator |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| etanercept | Drug | will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Persistence of inactive disease | Inactive disease is defined by the criterion of Wallace :
For all the visits, joint counts and physician global assessment of disease activity will be performed by an investigator blinded from patient study group. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse and serious adverse events or of special interest | Weeks 12, 24, 36, 48, 60, 72 | |
| Persistent inactive disease as defined by Wallace criteria | 72 weeks | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Florence UETTWILLER, PhD | Necker Children's Hospital, Paris, France | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Necker Children's Hospital | Paris | Paris | 75015 | France |
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| ID | Term |
|---|---|
| D001171 | Arthritis, Juvenile |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D000068800 | Etanercept |
| D000068879 | Adalimumab |
| D000069594 | Abatacept |
| C502936 | tocilizumab |
| ID | Term |
|---|---|
| D007141 | Immunoglobulin Fc Fragments |
| D007128 | Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
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| adalimumab | Drug | will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks |
|
|
| Abatacept | Drug | will be tapered from every 4 weeks to every 6 weeks for 24 weeks |
|
|
| Tocilizumab | Drug | will be tapered from every 4 weeks to every 6 weeks for 24 weeks |
|
|
| Juvenile Arthritis Disease Activity Score (JADA score) |
| Day 0, Weeks 12, 24, 48, 72 |
| Biological agent concentrations | according to drug administration (Etanercept or Abatacept or Tocilizumab or Adalimumab) | Day 0, weeks 12, 24, 36, 48, 60 |
| Anti-drugs antibodies concentrations | anti-Etanercept or anti-Abatacept or anti-Tocilizumab or anti-Adalimumab | Day 0, weeks 12, 24, 36, 48, 60 |
| Proteins S100 concentrations (MRP8/14 level) | Day 0, weeks 24, 48, 72 |
| Concentration of additional informative markers (cytokines, chemokines) | Day 0, weeks 24, 48, 72 |
| score of quality of life with the Paediatric Quality of Life (PedsQL) | Day 0, weeks 24, 36, 72 |
| score of quality of life with the Childhood Health Assessment Questionnaire (CHAQ) | Day 0, weeks 12, 24, 36, 72 |
| score of quality of life with the Life Quality Questionnaire related to the health (EQ-5D Y) | Day 0, weeks 24, 36, 72 |
| cost of early treatment tapering and withdrawal | weeks 12, 24, 36, 60, 72 |
| cost of late treatment tapering and withdrawal | weeks 12, 24, 36, 60, 72 |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D007127 | Immunoglobulin Constant Regions |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D018124 | Receptors, Tumor Necrosis Factor |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D018796 | Immunoconjugates |