Effects of the use of growth hormone in children and adolescents with juvenile idiopathic arthritis: a systematic review

Frittoli, Renan Bazuco; Longhi, Barbara Sugui; Silva, Amanda Meireles; Barros, Antônio de Azevedo; Monteiro, Maria Ângela Reis de Góes; Appenzeller, Simone

doi:10.1016/j.rbre.2016.07.009

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Revista Brasileira de Reumatologia

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Original articles • Rev. Bras. Reumatol. 57 (2) • Mar-Apr 2017 • https://doi.org/10.1016/j.rbre.2016.07.009 copy

Effects of the use of growth hormone in children and adolescents with juvenile idiopathic arthritis: a systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction:

Children with juvenile idiopathic arthritis (JIA) often have impaired growth and short stature. There is evidence that the therapeutic use of growth hormone (GH) is useful and safe in these patients.

Objective:

To analyze the effects of GH use in patients with JIA.

Method:

A systematic review of the literature over the last 18 years in Medline and Embase databases. The criteria were analyzed independently by the researchers. We used the following keywords: "growth hormone", "arthritis, juvenile", "arthritis, rheumatoid", "child" and "adolescent".

Results:

Among the 192 identified articles, 20 corresponded to the inclusion criteria. Seventeen longitudinal studies and 3 case reports were found. Most studies analyzed observed increased growth, muscle mass and bone mass using GH. Adverse effects observed were glucose intolerance, diabetes, bone deformities, osteonecrosis, reactivation of the disease and low final height.

Conclusion:

The majority of studies reported positive effects after the therapeutic use of GH, but some variability in response to treatment was observed. The combination of growth hormone with other drugs seems to be a good option.

Keywords:
Artrite idiopática juvenil; Hormônio de crescimento; Crianças; Adolescentes

Article	Sample	Age group (years)	Disease duration (years)	GH dose (mg/kg/day)	Treatment duration (years)	GH effect
Bechtold, 2012¹¹11 Bechtold S, Beyerlein A, Ripperger P, Roeb J, Dalla PR, Hafner R, et al. Total pubertal growth in patients with juvenile idiopathic arthritis treated with growth hormone: analysis of a single center. Growth Horm IGF Res. 2012;22:180-5. (Deutschland)	39 patients (systemic/polyarticular JIA) 24 controls	(8-13)	≅5	0.047	6.32 ± 1.96	GH had positive effects on height and pubertal development
Bismuth E, 2010²⁸28 Bismuth EA, Chevenne DB, Czernichow PA, Simon DA. Moderate deterioration in glucose tolerance during high-dose growth hormone therapy in glucocorticoid-treated patients with juvenile idiopathic arthritis. Horm Res Paediatr. 2010;73:465-72. (France)	43 patients (systemic/polyarticular JIA) 15 controls	(4-14) (4-8)	3.9 ± 2.7 4.3 ± 2.9	0.065	3	GH combined with glucocorticoids was associated with a significant increase in fasting insulin level
Bechtold, 2010¹²12 Bechtold S, Ripperger P, Dalla PR, Roth J, Hafner R, Michels H, et al. Dynamics of body composition and bone in patients with juvenile idiopathic arthritis treated with growth hormone. J Clin Endocrinol Metab. 2010;95:178-85. (Deutschland)	12 patients (systemic/polyarticular JIA)	(9-14)	8.49 ± 2.9	-	5.35 ± 0.7	Benefits in anthropometric levels, and fat levels stabilized
Bechtold, 2007¹³13 Bechtold S, Ripperger P, Dalla PR, Bonfig W, Hafneer R, Michels H. Growth hormone increases final height in patients with juvenile idiopathic arthritis: data from a randomized controlled study. J Clin Endocrinol Metab. 2007;92:3013-8. (Deutschland)	31 patients (systemic/polyarticular JIA) 18 controls	(10-14)	3,7 ± 1,2	0.047	8.4	Patients reached the height within the standard target set
Simon, 2007¹⁴14 Simon D, Prieur AM, Quartier P, Charles Ruiz J, Czernichow P. Early recombinant human growth hormone treatment in glucocorticoid-treated children with juvenile idiopathic arthritis: a 3-year randomized study. J Clin Endocrinol Metab. 2007;92:2567-73. (France)	30 patients (systemic/polyarticular JIA)	(7-12)	-	0.065	3	Benefits in anthropometric levels Bone mineralization with no significant difference Increased blood glucose
Bechtold, 2005¹⁵15 Bechtold S, Ripperger P, Bonfig W, Pozza RD, Haefner R, Schwarz HP. Growth hormone changes bone geometry and body composition in patients with juvenile idiopathic arthritis requiring glucocorticoid treatment: a controlled study using peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005;90:3168-73. (Deutschland)	17 patients (systemic/polyarticular JIA)	(12-17)	8.2 ± 4.4	(0.036-0.047)	4	GH had positive and significant effects on height and muscle mass
Saha, 2004¹⁶16 Saha MT, Haapasaari J, Hannula S, Sarna S, Lenko HL. Growth hormone is effective in the treatment of severe growth retardation in children with juvenile chronic arthritis. Double blind placebo-controlled followup study. J Rheumatol. 2004;31:1413-7. (Finland)	25 patients (12 polyarticular JIA, 10 oligoarticular JIA and 3 systemic JIA)	(8-11)	-	0.033	0.5 (6 months)	Patients with GH treatment grew faster versus control group
Bechtold, 2004¹⁷17 Bechtold S, Ripperger P, Bonfig W, Schmidt H, Bitterling H, Hafner R, et al. Bone mass development and bone metabolism in juvenile idiopathic arthritis. J Rheumatol. 2004;31:1407-12. (Deutschland)	11 patients (systemic/polyarticular JIA)	(9-11)	3.7 ± 1.4	0.047	4	Significant increase in height, and improvement in bone remodeling
Bechtold, 2003¹⁸18 Bechtold S, Ripperger P, Häfner R, Said E, Schwarz HP. Growth hormone improves height in patients with juvenile idiopathic arthritis: 4-year data of a controlled study. J Pediatr. 2003;143:512-9. (Deutschland)	38 patients (systemic/polyarticular JIA)	(5.5-13.8)	≅3.8	(0.028-0.047)	4	Significant increase in final height
Simon, 2003¹⁹19 Simon D, Lucidarme N, Prieur AM, Ruiz JC, Czernichow P. Effects on growth and body composition of growth hormone treatment in children with juvenile idiopathic arthritis requiring steroid therapy. J Rheumatol. 2003;30:2492-9. (France)	30 patients (systemic/polyarticular JIA)	(6.8-13.0)	8.2 (4.5-15.6)	0.065	3	Improvement in growth rate Increases in lean body mass and bone mineral density Glucose intolerance observed in 6 patients Increase of glycosylated hemoglobin
Simon, 2001⁵5 Simon D, Lucidarme N, Prieur AM, Ruiz JC. Czernichow linear growth in children suffering from juvenile idiopathic arthritis requiring steroid therapy: natural history and effects of growth hormone treatment on linear growth. J Pediatr Endocrinol Metab. 2001;6:1483-6. (France)	14 patients (systemic/polyarticular JIA)	≅9.7	≅3	0.065	1	Improved growth rate and prevention of metabolic complications
Al-Mutair, 2000²⁰20 Al-Mutair A, Bahabri S, Al-Mayouf S, Al-Ashwal A. Efficacy of recombinant human growth hormone in children with juvenile rheumatoid arthritis and growth failure. J Pediatr Endocrinol Metab. 2000;13:899-905. (Saudi Arabia)	10 patients (systemic/polyarticular JIA)	(6-15)	-	0.027	1 and 3	Improved growth in the final height One patient developed deformities in both knees
Touati, 2000²¹21 Touati G, Ruiz JC, Porquet D, Kindermans C, Prieur AM, Czernichow P. Effects on bone metabolism of one year recombinant human growth hormone administration to children with juvenile chronic arthritis undergoing chronic steroid therapy. J Rheumatol. 2000;27:1287-93. (France)	14 patients (systemic/polyarticular JIA)	(6-14)	≅3	0.066	1	Significant increases in bone resorption markers Plasma level of osteocalcin was the best variable predictive of growth
Rooney, 2000²²22 Rooney M, Davies UM, Reeve J, Preece M, Ansell BM, Woo PM. Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis. J Rheumatol. 2000;27:1073-81. (England)	20 patients (systemic/polyarticular JIA)	7.6	-	-	1	Improvement of bone metabolism and height
Simon, 2000²³23 Simon D, Prieur A, Czernichow P. Treatment of juvenile rheumatoid arthritis with growth hormone. Horm Res. 2000;53:82-6. (France)	14 patients (systemic/polyarticular JIA)	≅9	-	0.06	2	Increases in growth rate and lean mass Increase in bone mineral density
Simon, 1999²⁴24 Simon D, Touati G, Prieur AM, Ruiz JC, Czernichow P. Growth hormone treatment of short stature and metabolic dysfunction in juvenile chronic arthritis. Acta Paediatr Suppl. 1999;88:100-5. (France)	14 patients (systemic/polyarticular JIA)	(9-12)	3 (9 months to ≅8 years)	0.067	1	Improvement in growth rate Decrease in glucose tolerance and increase in glycosylated hemoglobin levels
Touati, 1998²⁵25 Touati G, Prieur AM, Ruiz JC, Noel M, Czernichow P. Beneficial effects of one-year growth hormone administration to children with juvenile chronic arthritis on chronic steroid therapy. I. Effects on growth velocity and body composition. J Clin Endocrinol Metab. 1998;83:403-9. (France)	14 patients (systemic/polyarticular JIA)	≅9	-	0.066	1-2	Increase in growth Increase in lean mass and decrease in fat mass Increase of glucose tolerance and increase in glycosylated hemoglobin

Article	Sample	Age group (years)	Disease duration (years ± SD)	GH dose (mg/kg/day)	Treatment duration (years)	GH effect
Kim, 2014⁹9 Kim JY, Kim HS, Park SH. Disease flare after 7 year-remission of systemic type juvenile idiopathic arthritis: is growth hormone therapy a culprit or innocent bystander. Int J Rheum. 2015;18:377-8. (South Korea)	1 patient (Systemic JIA)	16	7	0.04	0.75 (9 months)	GH had positive effects on height Possible effect of GH on the reactivation of the disease
Nikishina, 2011¹⁰10 Nikishina IP, Rodionovskaya SR, Shapovalenko AN, Filippova LY, Jostareva OM. An experience of sequental use of three biologics and recombinant growth hormone in a patient with juvenile idiopathic arthritis associated with unsuccessful outcome of hip damage. Pediatr Rheumatol. 2011;9:143. (Russia)	1 patient (polyarticular JIA)	14	-	0.05	-	GH had positive effects on height Possible effect of GH in the development of osteonecrosis
Pun, 2011²⁷27 Pun T, Chandurkar V. Growth hormone deficiency, short stature, and juvenile rheumatoid arthritis in a patient with autoimmune polyglandular syndrome type 1: case report and brief review of the literature. ISRN Endocrinol. 2011;2011:62759. (Canada)	1 patient (JIA + Autoimmune polyglandular syndrome type 1)	16	13	-	-	Atypical findings including growth hormone deficiency even with use of the treatment, short stature

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[1] *Corresponding author. E-mail: appenzellersimone@yahoo.com (S. Appenzeller).