Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: A randomized clinical trial

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Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis

in remission: A randomized clinical trial

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JAMA, 04/07/10

The objective of this study was to analyze whether longer methotrexate

treatment during remission of JIA prevents flares after withdrawal of

medication and whether specific biomarkers identify patients at risk for

flares. In patients with JIA in remission, a 12-month vs 6-month withdrawal

of methotrexate did not reduce the relapse rate. Higher MRP8/14

concentrations were associated with risk of relapse after discontinuing

methotrexate.

Methods

Prospective, open, multicenter, medication-withdrawal randomized clinical

trial including 364 patients (median age, 11.0 years) with JIA recruited in

61 centers from 29 countries between February 2005 and June 2006

Patients were included at first confirmation of clinical remission while

continuing medication

At the time of therapy withdrawal, levels of the phagocyte activation marker

myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined

Patients randomly assigned to continue with methotrexate therapy for either

6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after

induction of disease remission

Primary outcome was relapse rate in 2 treatment groups; secondary outcome

was time to relapse

In a prespecified cohort analysis, the prognostic accuracy of MRP8/14

concentrations for the risk of flares was assessed

Results

Intention-to-treat analysis of the primary outcome revealed relapse within

24 months after the inclusion into the study in 98 of 183 patients (relapse

rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2

OR for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P = .86)

Median relapse-free interval after inclusion was 21.0 months in group 1 and

23.0 months in group 2

HR for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P = .61)

Median follow-up duration after inclusion was 34.2 and 34.3 months in groups

1 and 2

Levels of MRP8/14 during remission were significantly higher in patients who

subsequently developed flares (median, 715 [iQR, 320-1 110] ng/mL) compared

with patients maintaining stable remission (400 [iQR, 220-800] ng/mL; P =

..003)

Low MRP8/14 levels indicated a low risk of flares within the next 3 months

following the biomarker test (area under the receiver operating

characteristic curve, 0.76; 95% CI, 0.62-0.90)