Withdrawal of Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis - Full Text View

Purpose

The purpose of this study is to determine whether etanercept can be withdrawn successfully (i.e. no occurrence of flares) in juvenile idiopathic arthritis (JIA) patients in whom disease remission is reached.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

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.
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.

Condition	Intervention	Phase
Juvenile Idiopathic Arthritis	Drug: etanercept	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	When and in Whom to Stop Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis

Resource links provided by NLM:

Genetics Home Reference related topics: juvenile idiopathic arthritis

MedlinePlus related topics: Juvenile Rheumatoid Arthritis

Drug Information available for: Etanercept

U.S. FDA Resources

Further study details as provided by Erasmus Medical Center:

Primary Outcome Measures:

Flare-rate [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
To evaluate if the flare-rate is different between the 2 arms (continuation and discontinuation of etanercept).

Secondary Outcome Measures:

Duration of remission before withdrawal of etanercept [ Time Frame: 9 months ] [ Designated as safety issue: No ]
To evaluate between the 2 arms (continuation and discontinuation of etanercept) if time in remission on etanercept is an important factor in retaining remission after discontinuation of etanercept.
Predictors for successful discontinuation of etanercept [ Time Frame: 12 months after discontinuation of etanercept ] [ Designated as safety issue: No ]
Evaluation of predictors (patient or disease characteristics, including time in remission, and MRP8/MRP14) for successful discontinuation of etanercept in all JIA patient who discontinue etanercept.
Disease course after flaring [ Time Frame: 6 months after flare ] [ Designated as safety issue: No ]
After a flare (exacerbation) occurs: evaluation of time to flare and the effect of restarting etanercept after flaring.


Estimated Enrollment:	50
Study Start Date:	January 2011
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: STOP-arm Discontinuation of etanercept	Drug: etanercept Discontinuation of etanercept (half of the dosis for 3 months and discontinuation thereafter) Other Name: enbrel
No Intervention: CONTROL-arm Continuation of etanercept for another 9 months, and, if still meeting the eligibility criteria, discontinuation of etanercept thereafter.	Drug: etanercept Continuation of etanercept for another 9 months, and, if still meeting the eligibility criteria, discontinuation of etanercept thereafter. Other Name: enbrel

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


Ages Eligible for Study:	4 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287715

Contacts


Contact: LWA van Suijlekom-Smit, MD,PhD,MSCE	+31-10-7036146	l.vansuijlekom@erasmusmc.nl
Contact: MH Otten, MD	+31-10-7036778	m.otten@erasmusmc.nl

Locations


Netherlands
Academic Medical Centre Emma Children's Hospital	Not yet recruiting
Amsterdam, Netherlands
Contact: MAJ van Rossum, MD, PhD m.a.vanrossum@amc.uva.nl
Principal Investigator: MAJ van Rossum, MD, PhD
Reade Institute Amsterdam	Not yet recruiting
Amsterdam, Netherlands
Contact: MAJ van Rossum, MD, PhD m.a.vanrossum@amc.uva.nl
Principal Investigator: MAJ van Rossum, MD, PhD
Sint-Lucas Andreas Hospital	Active, not recruiting
Amsterdam, Netherlands
University Medical Centre Groningen	Not yet recruiting
Groningen, Netherlands
Contact: W Armbrust, MD, PhD w.armbrust@bkk.umcg.nl
Principal Investigator: W Armbrust, MD, PhD
Leiden University Medical Center	Not yet recruiting
Leiden, Netherlands
Contact: R ten Cate, MD, PhD r.tencate@lumc.nl
Principal Investigator: R ten Cate, MD, PhD
Maastricht University Medical Centre	Not yet recruiting
Maastricht, Netherlands
Contact: SL Gorter, MD, PhD sgo@sint.azm.nl
Principal Investigator: SL Gorter, MD, PhD
St Maartenskliniek	Not yet recruiting
Nijmegen, Netherlands
Contact: EPAH Hoppenreijs, MD, PhD e.hoppenreijs@cukz.umcn.nl
Principal Investigator: EPAH Hoppenreijs, MD, PhD
Erasmus MC Sophia Children's Hospital	Recruiting
Rotterdam, Netherlands
Contact: LWA van Suijlekom-Smit, MD,PhD,MSCE l.vansuijlekom@erasmusmc.nl
Principal Investigator: LWA van Suijlekom-Smit, MD,PhD,MSCE
Haga Hospital, Juliana Children's Hospital	Not yet recruiting
The Hague, Netherlands
Contact: Y Koopman, MD y.koopman@hagaziekenhuis.nl
Principal Investigator: Y Koopman, MD
Utrecht Medical Centre Wilhelmina Children's Hospital	Not yet recruiting
Utrecht, Netherlands
Contact: R van Royen, MD, PhD a.vanroyen@umcutrecht.nl
Principal Investigator: A van Royen, MD, PhD

Sponsors and Collaborators

Erasmus Medical Center

Dutch Arthritis Association

Investigators


Principal Investigator:	LWA van Suijlekom-Smit, MD,PhD,MSCE	Erasmus Medical Center

More Information

Additional Information:

Link to ABC-register (observational study including all JIA patients who use biological agents in The Netherlands) This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	L.W.A. van Suijlekom-Smit, MD, PhD, MSCE, Erasmus Medical Center Sophia Children's Hospital
ClinicalTrials.gov Identifier:	NCT01287715 History of Changes
Other Study ID Numbers:	NR 10-1-203
Study First Received:	January 31, 2011
Last Updated:	January 31, 2011
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:


Arthritis Arthritis, Juvenile Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Immunoglobulin G TNFR-Fc fusion protein Analgesics Analgesics, Non-Narcotic	Anti-Inflammatory Agents Anti-Inflammatory Agents, Non-Steroidal Antirheumatic Agents Central Nervous System Agents Gastrointestinal Agents Immunologic Factors Immunosuppressive Agents Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Sensory System Agents Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015

Withdrawal of Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis (ABC-STOP)