ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 9.15 | DOI: 10.1530/ey.16.9.15

Paediatric Rheumatology International Trials Organisation and the Pediatric Rheumatology Collaborative Study Group


To read the full abstract: J Rheumatol. 2018; 45(8): 1173

In recent years, biologic agents have clearly been shown to be effective in maintaining remission and improving linear growth in children with inflammatory bowel disease and other chronic inflammatory diseases (1–3). This prospective cohort study analyzed growth in 187 patients (143 females, mean age 11±4 years; including 123 with Tanner stage ≤3 at baseline) with polyarticular-course juvenile idiopathic arthritis treated with the biologic drug tocilizumab, an anti-Interleukin-6 (IL-6) receptor antibody. Tocilizumab was associated with improved growth profiles from baseline to the end of the second year of therapy: height SDS increased in 72% of patients, with mean height gain +0.40 SDS.

The study did not include essential auxological elements, such as target height and bone age evaluation. Patients with chronic inflammatory diseases often show pubertal delay and blunted pubertal growth spurt; for these reasons Tanner stage assessment was planned at “selected visits”, but the pubertal progression was neither analysed nor commented on. A further limitation is the lack of laboratory measurements, such as IGF-1 and bone turnover markers. Finally, a significant proportion of patients (46%) were concurrently treated with steroids, but the impact of steroid therapy dose and duration on growth was not considered.

IL-6 appears to be the major proinflammatory cytokine involved in growth retardation in chronic inflammatory diseases. Previously, a 50% to 70% reduction in growth rate was observed in transgenic mice expressing high levels of circulating IL-6, associated with low IGF-1 levels and partially reversed by the administration of an anti–IL-6 receptor antibody (4). The pathophysiological link between IL-6 and IGF-1 is clearly interesting, but a more complete evaluation of the factors interfering with linear growth and pubertal spurt is needed.

The therapeutic switch from chronic glucocorticoid therapy to the use of biologic agents has profoundly changed the clinical scenario of chronic inflammatory diseases, even if a few data suggest a vanishing effect with time. A role of biological agents in improving growth of patients with chronic inflammatory diseases has been suggested by previous studies (1–3), and this effect has been directly correlated with early response to therapy and sustained remission. Nevertheless, new longitudinal studies should include an accurate assessment of height velocity, puberty, essential laboratory data, and confounding effects of steroid treatment.

References: 1. Marino A, Stagi S, Simonini G, Carli N, Caparello MC, Giani T, Pagnini I, De Masi S, Cimaz R. Growth and body mass index in a cohort of patients with juvenile idiopathic arthritis: effects of second line treatments. Clin Exp Rheumatol. 2018; 36: 929–933.

2. Church PC, Guan J, Walters TD, Frost K, Assa A, Muise AM, Griffiths AM. Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn’s disease. Inflamm Bowel Dis. 2014; 20: 1177–1186.

3. Walters TD, Faubion WA, Griffiths AM, Baldassano RN, Escher J, Ruemmele FM, Hyams JS, Lazar A, Eichner S, Huang B, Li Y, Thakkar RB. Growth Improvement with Adalimumab Treatment in Children with Moderately to Severely Active Crohn’s Disease. Inflamm Bowel Dis. 2017; 23: 967–975.

4. De Benedetti F, Alonzi T, Moretta A, Lazzaro D, Costa P, Poli V, Martini A, Ciliberto G, Fattori E. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J Clin Invest 1997; 99: 643–650.

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