Treatment Tapering in JIA With Inactive Disease (AJIBIOREM)

March 19, 2026 updated by: Assistance Publique - Hôpitaux de Paris

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Paris
      • Paris, Paris, France, 75015
        • Necker Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 17 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: etanercept
will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks
Other Names:
  • Enbrel®
Drug: adalimumab
will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks
Other Names:
  • Humira®
Drug: Abatacept
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
  • Orencia®
Drug: Tocilizumab
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
  • RoActemra®
Active Comparator: Control
  • 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.
Drug: etanercept
will be tapered from every week to every 2 weeks for 12 weeks then to every 3 weeks for 12 weeks
Other Names:
  • Enbrel®
Drug: adalimumab
will be tapered from every 2 weeks to every 3 weeks for 12 weeks and to every 4 weeks for 12 weeks
Other Names:
  • Humira®
Drug: Abatacept
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
  • Orencia®
Drug: Tocilizumab
will be tapered from every 4 weeks to every 6 weeks for 24 weeks
Other Names:
  • RoActemra®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse and serious adverse events or of special interest
Time Frame: Weeks 12, 24, 36, 48, 60, 72
Weeks 12, 24, 36, 48, 60, 72
Persistent inactive disease as defined by Wallace criteria
Time Frame: 72 weeks
72 weeks
Juvenile Arthritis Disease Activity Score (JADA score)
Time Frame: Day 0, Weeks 12, 24, 48, 72
Day 0, Weeks 12, 24, 48, 72
Biological agent concentrations
Time Frame: Day 0, weeks 12, 24, 36, 48, 60
according to drug administration (Etanercept or Abatacept or Tocilizumab or Adalimumab)
Day 0, weeks 12, 24, 36, 48, 60
Anti-drugs antibodies concentrations
Time Frame: Day 0, weeks 12, 24, 36, 48, 60
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)
Time Frame: Day 0, weeks 24, 48, 72
Day 0, weeks 24, 48, 72
Concentration of additional informative markers (cytokines, chemokines)
Time Frame: Day 0, weeks 24, 48, 72
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
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
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
Day 0, weeks 24, 36, 72
cost of early treatment tapering and withdrawal
Time Frame: weeks 12, 24, 36, 60, 72
weeks 12, 24, 36, 60, 72
cost of late treatment tapering and withdrawal
Time Frame: weeks 12, 24, 36, 60, 72
weeks 12, 24, 36, 60, 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
URC-CIC Paris Descartes Necker Cochin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Florence UETTWILLER, PhD, Necker Children's Hospital, Paris, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 18, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 29, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 19, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 20, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P 150902
  • 2016-000312-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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