Juvenile Idiopathic ArthritisPhase 3AJIBIOREMNCT02840175
Treatment Tapering in JIA With Inactive Disease
A Phase 3 study testing etanercept, adalimumab and Abatacept in people with Juvenile Idiopathic Arthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Juvenile Idiopathic Arthritis
- What is being tested?
- etanercept, adalimumab and Abatacept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteFrance
- Study dates
- 18 May 2017to 1 Oct 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patient aged 2 to 17 years and treated with etanercept or tocilizumab or adalimumab, or patient aged 6 to 17 years and treated with abatacept.
- Patient with an oligoarticular or polyarticular rheumatoid factor negative JIA
- Patient treated with biologic treatment for persistent arthritis according to the marketing authorization.
- Patient who achieved inactive disease within two years of treatment with the last biologic agent administered, according to Wallace criteria : no joints with active arthritis, no active uveitis (as defined by the SUN Working Group), ESR or CRP level within normal limits in the laboratory where tested (or, if elevated, not attributable to JIA), physician's global assessment of disease activity score (< 10/100 visual analogue scale), and duration of morning stiffness < ou = 15 minutes (within 7 days before the visit).
- Patient with inactive disease achieved for less than 12 months.
- Patient with stable doses of non-steroidal anti-inflammatory drugs, Methotrexate (maximum 20 mg/m2/week), and other non biologic DMARD for at least one month before inclusion
Show all 9Show fewer
- Patient without steroids or joint injection or live vaccines injection for at least one month.
- Signed informed consent by both parents (or legal guardian) and patient's agreement.
- Patient affiliated to the National Health Assurance system.
Who cannot join
- Patient with systemic form, rheumatoid factor positive, psoriatic or associated with enthesitis related JIA.
- Patient undergoing biologic therapy due to JIA-associated uveitis or with active uveitis at time of randomization.
- Patient with any contraindication to continue ongoing biologic treatment, notably ongoing uncontrolled infection, suspicion or evidence of demyelinating disease of the central nervous system.
- Patient previously treated with the same biotherapy for which dose decreasing or biotherapy withdrawal was already tested in the past for inactive disease and then reintroduced.
- Pregnancy or absence of effective contraception (including abstinence) in a pubertal patient.
- Patient suffering from tuberculosis.
- Patient with moderate to severe cardiac failure (NYHA class III / IV).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment Tapering in Oligoarticular or Rheumatoid Factor Negative Polyarticular Juvenile Idiopathic Arthritis With Inactive Disease on Biologic Therapy
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.
Read the detailed description
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.
- Conditions
- Juvenile Idiopathic Arthritis
- Being tested
- etanercept, adalimumab, Abatacept, Tocilizumab
- Keywords
- Treatment tapering, Oligoarticular, Juvenile Idiopathic Arthritis, Inactive disease, Biologic therapy
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etanerceptDrug
Also called Enbrel®
will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks
adalimumabDrug
Also called Humira®
will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks
AbataceptDrug
Also called Orencia®
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
TocilizumabDrug
Also called RoActemra®
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | * Day 0 at Weeks 24 : Increase the interval between 2 doses of the biological agent (etanercept, adalimumab, tocilizumab, abatacept)
* Weeks 24 at Weeks 72: Stop the biological agent if inactive disease is maintained. Receives: Drug: etanercept; Drug: adalimumab; Drug: Abatacept; Drug: Tocilizumab |
| Control | Active comparator | * Day 0 at Weeks 24: Maintain the biological agent (etanercept, adalimumab, tocilizumab, abatacept) at the same dose.
* Weeks 24 at Weeks 48 : Increase the interval between 2 doses of the biological agent.
* Weeks 48 at Weeks 72: Stop the biological agent if inactive disease is maintained. Receives: Drug: etanercept; Drug: adalimumab; Drug: Abatacept; Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Persistence of inactive disease
Inactive disease is defined by the criterion of Wallace :
- No joints with active arthritis,
- No active uveitis as defined by the SUN Working Group2 (The Standardization of Uveitis Nomenclature (SUN) Working Group defines inactive anterior uveitis as "grade zero cells," indicating <1 cell in field sizes of 1 mm by a 1-mm slit beam),
- Erythrocyte sedimentation rate (ESR) ≤ 20 mm or C-reactive protein (CRP) level ≤ 10 mg/L (or ≤ 1 mg/dl or ≤ 100 µg/dl) or, if elevated, not attributable to JIA (if both ESR and CRP are available, both of them should be in the normal range)
- Physician's global assessment of disease activity score (< 10/100 visual analogue scale),
- and duration of morning stiffness < or egal to 15 minutes (within 7 days before the visit).
For all the visits, joint counts and physician global assessment of disease activity will be performed by an investigator blinded from patient study group.
Measured: 24 weeks
Secondary outcomes (12)
Adverse and serious adverse events or of special interest
Measured: Weeks 12, 24, 36, 48, 60, 72
Persistent inactive disease as defined by Wallace criteria
Measured: 72 weeks
Juvenile Arthritis Disease Activity Score (JADA score)
Measured: Day 0, Weeks 12, 24, 48, 72
Biological agent concentrations
according to drug administration (Etanercept or Abatacept or Tocilizumab or Adalimumab)
Measured: Day 0, weeks 12, 24, 36, 48, 60
Anti-drugs antibodies concentrations
anti-Etanercept or anti-Abatacept or anti-Tocilizumab or anti-Adalimumab
Measured: Day 0, weeks 12, 24, 36, 48, 60
Proteins S100 concentrations (MRP8/14 level)
Measured: Day 0, weeks 24, 48, 72
Concentration of additional informative markers (cytokines, chemokines)
Measured: Day 0, weeks 24, 48, 72
score of quality of life with the Paediatric Quality of Life (PedsQL)
Measured: Day 0, weeks 24, 36, 72
score of quality of life with the Childhood Health Assessment Questionnaire (CHAQ)
Measured: Day 0, weeks 12, 24, 36, 72
score of quality of life with the Life Quality Questionnaire related to the health (EQ-5D Y)
Measured: Day 0, weeks 24, 36, 72
cost of early treatment tapering and withdrawal
Measured: weeks 12, 24, 36, 60, 72
cost of late treatment tapering and withdrawal
Measured: weeks 12, 24, 36, 60, 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2016 (estimated)
- Study start18 May 2017
- Primary completion29 Oct 2019
- Study completion1 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Juvenile Idiopathic ArthritisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Florence UETTWILLER, PhD, Study chair, Necker Children's Hospital, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02840175
- Sponsor's protocol ID
- P 150902
- Other IDs
- 2016-000312-15, 2016
- Acronym
- AJIBIOREM
- Status last verified
- Mar 2026
- First submitted
- 19 Jul 2016
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Tapering in Oligoarticular or Rheumatoid Factor Negative Polyarticular Juvenile Idiopathic Arthritis With Inactive Disease on Biologic Therapy
- ClinicalTrials.gov ID
- NCT02840175
- Acronym / sponsor ID
- AJIBIOREM / P 150902
- Conditions
- Juvenile Idiopathic Arthritis
- Keywords
- Treatment tapering, Oligoarticular, Juvenile Idiopathic Arthritis, Inactive disease, Biologic therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 18 May 2017 (actual)
- Primary completion
- 29 Oct 2019 (actual)
- Study completion
- 1 Oct 2020 (actual)
- First posted
- 21 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: etanercept, Drug: adalimumab, Drug: Abatacept, Drug: Tocilizumab* Day 0 at Weeks 24 : Increase the interval between 2 doses of the biological agent (etanercept, adalimumab, tocilizumab, abatacept) * Weeks 24 at Weeks 72: Stop the biological agent if inactive disease is maintained. |
| Control | Active comparator | Drug: etanercept, Drug: adalimumab, Drug: Abatacept, Drug: Tocilizumab* Day 0 at Weeks 24: Maintain the biological agent (etanercept, adalimumab, tocilizumab, abatacept) at the same dose. * Weeks 24 at Weeks 48 : Increase the interval between 2 doses of the biological agent. * Weeks 48 at Weeks 72: Stop the biological agent if inactive disease is maintained. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Patient aged 2 to 17 years and treated with etanercept or tocilizumab or adalimumab, or patient aged 6 to 17 years and treated with abatacept.
- Patient with an oligoarticular or polyarticular rheumatoid factor negative JIA
- Patient treated with biologic treatment for persistent arthritis according to the marketing authorization.
- Patient who achieved inactive disease within two years of treatment with the last biologic agent administered, according to Wallace criteria : no joints with active arthritis, no active uveitis (as defined by the SUN Working Group), ESR or CRP level within normal limits in the laboratory where tested (or, if elevated, not attributable to JIA), physician's global assessment of disease activity score (< 10/100 visual analogue scale), and duration of morning stiffness < ou = 15 minutes (within 7 days before the visit).
- Patient with inactive disease achieved for less than 12 months.
Key exclusion criteria (7 listed)
- Patient with systemic form, rheumatoid factor positive, psoriatic or associated with enthesitis related JIA.
- Patient undergoing biologic therapy due to JIA-associated uveitis or with active uveitis at time of randomization.
- Patient with any contraindication to continue ongoing biologic treatment, notably ongoing uncontrolled infection, suspicion or evidence of demyelinating disease of the central nervous system.
- Patient previously treated with the same biotherapy for which dose decreasing or biotherapy withdrawal was already tested in the past for inactive disease and then reintroduced.
- Pregnancy or absence of effective contraception (including abstinence) in a pubertal patient.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etanerceptAlso: Enbrel®will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks | Drug | Control, Experimental |
| adalimumabAlso: Humira®will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks | Drug | Control, Experimental |
| AbataceptAlso: Orencia®will be tapered from every 4 weeks to every 6 weeks for 24 weeks | Drug | Control, Experimental |
| TocilizumabAlso: RoActemra®will be tapered from every 4 weeks to every 6 weeks for 24 weeks | Drug | Control, Experimental |
Primary outcome
Persistence of inactive disease
Time frame: 24 weeks
Inactive disease is defined by the criterion of Wallace : * No joints with active arthritis, * No active uveitis as defined by the SUN Working Group2 (The Standardization of Uveitis Nomenclature (SUN) Working Group defines inactive anterior uveitis as "grade zero cells," indicating <1 cell in field sizes of 1 mm by a 1-mm slit beam), * Erythrocyte sedimentation rate (ESR) ≤ 20 mm or C-reactive protein (CRP) level ≤ 10 mg/L (or ≤ 1 mg/dl or ≤ 100 µg/dl) or, if elevated, not attributable to JIA (if both ESR and CRP are available, both of them should be in the normal range) * Physician's global assessment of disease activity score (< 10/100 visual analogue scale), * and duration of morning stiffness < or egal to 15 minutes (within 7 days before the visit). For all the visits, joint counts and physician global assessment of disease activity will be performed by an investigator blinded from patient study group.
12 secondary outcomes
Adverse and serious adverse events or of special interest
Time frame: Weeks 12, 24, 36, 48, 60, 72
Persistent inactive disease as defined by Wallace criteria
Time frame: 72 weeks
Juvenile Arthritis Disease Activity Score (JADA score)
Time frame: Day 0, Weeks 12, 24, 48, 72
Biological agent concentrations
Time frame: Day 0, weeks 12, 24, 36, 48, 60
Anti-drugs antibodies concentrations
Time frame: Day 0, weeks 12, 24, 36, 48, 60
Proteins S100 concentrations (MRP8/14 level)
Time frame: Day 0, weeks 24, 48, 72
Concentration of additional informative markers (cytokines, chemokines)
Time frame: Day 0, weeks 24, 48, 72
score of quality of life with the Paediatric Quality of Life (PedsQL)
Time frame: Day 0, weeks 24, 36, 72
score of quality of life with the Childhood Health Assessment Questionnaire (CHAQ)
Time frame: Day 0, weeks 12, 24, 36, 72
score of quality of life with the Life Quality Questionnaire related to the health (EQ-5D Y)
Time frame: Day 0, weeks 24, 36, 72
cost of early treatment tapering and withdrawal
Time frame: weeks 12, 24, 36, 60, 72
cost of late treatment tapering and withdrawal
Time frame: weeks 12, 24, 36, 60, 72
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Juvenile Idiopathic Arthritis
RecruitingPhase 3
A Study of Baricitinib in Participants From 1 Year to Less Than 18 Years Old With Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis
Recruiting
The Use of Infrared Cameras for Detecting Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis, Infrared Thermography
Not yet recruitingPhase 4
Withdrawal Versus Continued TNF Inhibitor Monotherapy Treatment in Children With Inactive Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis (JIA)
RecruitingObservational study
Tofacitinib in Juvenile Idiopathic Arthritis
Juvenile Idiopathic Arthritis (JIA)
RecruitingPhase 3
An Open-label Study to Evaluate the Pharmacokinetics and Safety of Bimekizumab in Pediatric Study Participants With Active Juvenile Idiopathic Arthritis Subtypes Enthesitis-related Arthritis (Including Juvenile-onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis
Enthesitis-related Arthritis, Juvenile Psoriatic Arthritis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florence UETTWILLER, PhD study chair
Necker Children's Hospital, Paris, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing etanercept, adalimumab and Abatacept in people with Juvenile Idiopathic Arthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Persistence of inactive disease (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.