A randomised trial of 6 months versus 12 months withdrawal of methotrexate in patients with Juvenile Idiopathic Arthritis (JIA) in clinical remission

• Register: ISRCTN
• Last refreshed on: 13 January 2015
• Main ID: ISRCTN18186313
• Date of registration: 16/02/2006
• Prospective Registration: No
• Primary sponsor: Pediatric Rheumatology International Trials Organisation (PRINTO) (Italy) and Wyeth Pharma
• Public title: A randomised trial of 6 months versus 12 months withdrawal of methotrexate in patients with Juvenile Idiopathic Arthritis (JIA) in clinical remission
• Date of first enrolment: 01/01/2005
• Target sample size: 300
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN18186313
• Study type: Interventional
• Study design: Prospective, randomised, clinical multi-centre study (Treatment)

Countries of recruitment

Argentina, Brazil, Chile, Croatia, Cuba, Czech Republic, Denmark, Finland, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Kuwait, Latvia, Mexico, Montenegro, Netherlands, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Slovakia, Spain, Switzerland, Turkey, United Kingdom

Contacts

• Name: Dirk Foell

Key inclusion & exclusion criteria

Inclusion criteria: Patients will be included at first confirmation of remission on medication i.e. after clinically documented inactive disease for at least three months (no joints with active arthritis, no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, no active uveitis, no elevation in Erythrocyte Sedimentation Rate [ESR] and/or C-Reactive Protein [CRP] attributable to JIA, physician?s global assessment of disease activity indicates no disease activity).

At three months, patients may be only be on a combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), low-dose steroids (0.2 mg/kg per day or 10 mg per day whichever is lower), and MTX (max 15 mg/m^2 per week); all the other drugs (e.g. biologics) must have been withdrawn before this date according to the physician?s decision.

Before inclusion into this study (study time point 0 months), patients will be considered to be in clinically documented remission on medication. At this time point, all medications other than NSAIDs and MTX with a dose range of 10 to 15 mg/m^2 per week have to be withdrawn. After discontinuation of MTX (study time point 6 i.e. after 6 months in group 1; study time point 12 i.e. after 12 months in group 2) treatment with NSAIDs should be stopped.
Exclusion criteria: Patients should not have received intra-articular corticosteroids up to three months prior to inclusion

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Juvenila Idiopathic Arthritis (JIA)
Musculoskeletal Diseases
Juvenila idiopathic arthritis

Intervention(s)

The study is designed as a prospective, randomised clinical trial with follow up documentation of 2 groups of patients.

Group 1:
At three months: first confirmation of remission on medication on the basis of signs of disease activity (no joints with active arthritis, no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, no active uveitis, no elevation in ESR and/or CRP attributable to JIA; physician?s global assessment of disease activity indicates no disease activity). At this point only on a combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), low-dose steroids (0.2 mg/kg per day or 10 mg per day whichever is lower), and MTX (max 15 mg/m^2 per week) is allowed, all the other drugs (e.g. biologics, intra-articular joint injections) must have been withdrawn before this date according to the physician decision. During the following three months low dose steroids and NSAIDS must be withdrawn according to the attending physician decision.

Time point zero months ? treatment with MTX is continued with dose range of 10 to 15 mg/m^2 per week (by oral, subcutaneous, intra-muscular or intravenous admission) after this time point. One NSAID is allowed.
Time point three months ? documentation of the clinical course after three months in remission.
6 months later ? confirmation of remission, discontinuation of MTX (and NSAID if applicable).

In further follow up examinations in intervals of three months the clinical course is documented over at least one year.

Group 2:
At time three months: first confirmation of remission on medication on the basis of signs of disease activity (no joints with active arthritis, fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA, no active uveitis, no elevation in ESR and/or CRP attributable to JIA, physician?s global assessment of disease activity indicates no disease activity). At this point only on a combination of Non-Steroidal Anti-Inflammatory Drugs (N

Primary Outcome(s)

Number of relapses

Secondary Outcome(s)

1. Time to relapse
2. Prediction of relapse by MRP8 or MRP14 serum concentrations

Secondary ID(s)

2005-001086-34

Source(s) of Monetary Support

Pediatric Rheumatology International Trials Organisation (PRINTO) (EU grant number 2001CVG4-808), Wyeth Pharma provided funding for patient insurance