Improvements in growth parameters in children with juvenile idiopathic arthritis associated with the effect of methotrexate on disease activity

Abstract

Objective. – To assess changes in growth parameters associated with the response to methotrexate (MTX) therapy in pre-pubertal children with juvenile idiopathic arthritis (JIA) and who had not been treated with steroids.

Methods. – We enrolled 27 pre-pubertal children with JIA who had been treated with MTX but not with steroids. The children were considered to have responded to treatment if the number of joints with active disease decreased by at least 50% 1 year after treatment initiation. We compared growth parameters (height, growth rate, weight and body mass index (BMI)) in responders and non-responders.

Results. – Twenty-one children (77.8%) responded to MTX therapy. The growth parameters were similar in the responders and non-responders before the onset of treatment. After 1 year, height (P = 0.025), growth rate (P = 0.03), weight (P = 0.007) and BMI (P = 0.05) increased significantly in the responder group, but not in the non-responder group. This increase was maintained for growth rate and weight after 2 and 3 years of treatment. After 1 year, height (P = 0.023) and growth rate (P = 0.0009) were significantly higher in the responders than in the non-responders, and these differences were still significant after 3 years (P = 0.01 and P = 0.033, respectively).

Conclusion. – In pre-pubertal children with JIA, a clinical response to MTX therapy is associated with a significant increase in growth parameters.

Introduction

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease. The polyarticular and systemic onset forms are often complicated by growth retardation. Local growth disturbances may be observed in the oligoarticular forms, but height and weight curves are normal. Growth retardation involves many factors, including 1) disease activity, resulting in low concentrations of insulin-like growth factor 1 (IGF1) [1], 2) poor nutritional status, with low protein and calorie intakes, and 3) prolonged corticosteroid therapy [2], [3], [4]. Bone mineral formation is also reduced in JIA, and is correlated with disease activity, whereas bone mineral resorption is normal [5]. Non-steroidal anti-inflammatory drugs (NSAID) can adequately control the disease activity in about one third of JIA patients [6], whereas more aggressive therapy is required in other patients. Methotrexate (MTX) is currently the most commonly used disease-modifying anti-rheumatic drug (DMARD) [6], [7], although new drugs such as etanercept have recently been shown to be effective for the control of polyarticular JIA [8]. MTX has been widely used in all subtypes of JIA since 1980 [9]. The clinical response rate ranges from 52 to 75% [10], [11], [12], [13]. However, MTX seems to be less effective in systemic onset forms [14], [15]. Tolerance is generally good [16], [17], [18], [19].

The aim of this study was to assess growth parameters associated with the response to MTX therapy in pre-pubertal children who had not been treated with steroids.