Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis

Abstract

Objective: To determine whether aggressive treatment initiated early in the course of rheumatoid factor (RF)-positive or RF-negative polyarticular juvenile idiopathic arthritis (JIA) can induce clinical inactive disease within 6 months.

Methods: Between May 2007 and October 2010, a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 2 aggressive treatments was conducted in 85 children ages 2-16 years with polyarticular JIA of <12 months' duration. Patients received either methotrexate (MTX) 0.5 mg/kg/week (maximum 40 mg) subcutaneously, etanercept 0.8 mg/kg/week (maximum 50 mg), and prednisolone 0.5 mg/kg/day (maximum 60 mg) tapered to 0 by 17 weeks (arm 1), or MTX (same dosage as arm 1), etanercept placebo, and prednisolone placebo (arm 2). The primary outcome measure was clinical inactive disease at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous clinical inactive disease) at 12 months.

Results: By 6 months, clinical inactive disease had been achieved in 17 (40%) of 42 patients in arm 1 and 10 (23%) of 43 patients in arm 2 (χ(2) = 2.91, P = 0.088). After 12 months, clinical remission on medication was achieved in 9 patients in arm 1 and 3 patients in arm 2 (P = 0.053). There were no significant interarm differences in adverse events.

Conclusion: Although this study did not meet its primary end point, early aggressive therapy in this cohort of children with recent-onset polyarticular JIA resulted in clinical inactive disease by 6 months and clinical remission on medication within 12 months of treatment in substantial proportions of patients in both arms.

Trial registration: ClinicalTrials.gov NCT00443430.

Figure 1

Treatment Arm 1: MTX 0.5mg/kg/wk subcutaneously (max 40 mg/wk) + daily prednisolone 0.5mg/kg/d (max 60 mg) with forced taper to zero by 17 wks + etanercept 0.8mg/kg/wk subcutaneously (max 50mg). Treatment Arm 2: MTX as in Arm 1 + placebo prednisolone tapered to zero + placebo etanercept injected weekly. Dark shaded boxes indicate the study flow for the patient if the end-points were achieved; Lighter shaded boxes indicate the study flow for the patient if the endpoints were not achieved. Solid lines represent the pivotal phase of the study. Dotted lines represent the exploratory phase of the study. Maximum total study duration = 12 months. CID = Clinical Inactive Disease CRM= Clinical Remission on Medications

FIGURE 2

Flow diagram of subject progress through the trial. Dark shaded boxes indicate assessments done under double-blind conditions.

FIGURE 3

Proportions of patients who had ACR pediatric 70 response rates (Figure 3A) and Clinical Inactive Disease (Figure 3B) at 1, 2, 4, 5, 6, and 12 months. Open = MTX, etanercept and prednisolone; Arm 1 = MTX, etanercept and prednisolone; Arm 2= MTX and placebo etanercept and placebo prednisolone.