Clinical trial NCT01287715: Withdrawal of Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis
Official title: When and in Whom to Stop Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Arthritis Association
First posted: 2011-02-01
Enrollment: 50
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether etanercept can be withdrawn successfully (i.e. no occurrence of flares) in juvenile idiopathic arthritis (JIA) patients in whom disease remission is reached.

Goals:

1. to investigate in a randomized controlled trial:

   * which proportion of JIA patients in remission can successfully discontinue etanercept compared to JIA patients in remission who continue etanercept;
   * if time in remission on etanercept is an important factor in retaining remission after discontinuation of etanercept.
2. to investigate in alle JIA patients who discontinue etanercept (including the control group):

   * predicting factors (patient or disease characteristics, including time in remission, and MRP8/MRP14) for successfully discontinuation of etanercept;
   * the disease course after discontinuation of etanercept (time to flare) and the effect of restarting etanercept after flaring.

Detailed description: Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in children. Etanercept has proven to be an effective treatment for JIA. Considering the risk of occurrence of long-term side-effects and to prevent the burden of the weekly injections and costs, it is a logical step to discontinue etanercept after reaching remission (no disease activity for at least six months). Especially since there are concerns about the long-term effect of suppressing the immune system with etanercept. However, little is known about if successful discontinuation is possible or when to stop. Risk is that the disease might flare (reactivate) again.

For this study, JIA patients in remission will be selected from the ABC-register (an observational study including all Dutch JIA patients who use etanercept). Eligible patients will be randomized to stop etanercept or continue it for another 9 months. Patients are followed with standard visits evaluating disease activity until 12 months after discontinuation of etanercept. In case of a disease flare etanercept therapy will be reintroduced immediately and the patient will be treated according to the insight of their treating physician. Expected is that JIA patients who were in remission for more than 12 months before discontinuation have a better chance to retain remission.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Juvenile Idiopathic Arthritis (all subtypes) by the International League of Associations of Rheumatology (ILAR) criteria
* On etanercept therapy
* No MTX or low dose MTX (maximum 10 mg/m2)
* 3 or more months in remission according to the criteria of Wallace (i.e. 9 or more months of inactive disease)
* Age ≥4 and \<18 years at start of study
* Written informed consent from parents and patients 12 years and over

Exclusion Criteria:

* Systemic corticosteroids (up to 9 months prior to inclusion)
* Intra-articular corticosteroids (up to 6 months prior to inclusion)
* Synthetic DMARDs besides low dose MTX (up to 9 months prior to inclusion)
* Biologic DMARDs besides etanercept (up to 9 months prior to inclusion)

Primary outcomes:
measure: Flare-rate
timeFrame: 9 months
Secondary outcomes:
measure: Duration of remission before withdrawal of etanercept
timeFrame: 9 months
measure: Predictors for successful discontinuation of etanercept
timeFrame: 12 months after discontinuation of etanercept
measure: Disease course after flaring
timeFrame: 6 months after flare
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre Emma Children's Hospital
city: Amsterdam
country: Netherlands
facility: Reade Institute Amsterdam
city: Amsterdam
country: Netherlands
facility: Sint-Lucas Andreas Hospital
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Nijmegen
country: Netherlands
facility: St Maartenskliniek
city: Rotterdam
country: Netherlands
facility: Erasmus MC Sophia Children's Hospital
city: The Hague
country: Netherlands
facility: Haga Hospital, Juliana Children's Hospital
city: Utrecht
country: Netherlands
facility: Utrecht Medical Centre Wilhelmina Children's Hospital
Study officials:
affiliation: Erasmus Medical Center
name: LWA van Suijlekom-Smit, MD,PhD,MSCE
role: PRINCIPAL_INVESTIGATOR
References: