Compliance to Growth Hormone Therapy in Children and Adolescents with Growth Hormone Deficiency and Turner Syndrome and Impact on Height Velocity: A Prospective Study
Keywords:Compliance, Growth Hormone Treatment, Adherence, Height Velocity, Growth Hormone Deficiency
Adherence to recombinant growth hormone (rGH) in children is necessary to ensure good treatment outcome. Reported non-compliance to rGH in children varied from 5-82% with little data involving Asian population. The objectives of this study are to evaluate the compliance of children and adolescents to rGH, effect of non-compliance on growth and factors affecting non-adherence. Methods: This is a prospective cohort study over 1-year aiming at all patients age less than 18 years old treated with rGH in our centre. Compliance was assessed from the number of returned medications and electronic record within device. Poor compliance was defined as utilised dose <86% prescribed (equivalent to missing injection ≥1 per week). Result: Thirty-four patients were recruited including 20 (59%) patients with GH deficiency and 14 (41%) with Turner syndrome. Poor compliance was noted in 35% of patients. Poor compliance in GHD patients was significantly associated with an older age (mean 12.55 ± 3.33 vs 9.28 ± 3.20 years old, p=0.038) and longer duration of treatment (mean 5.41 ± 3.0 vs 2.93 ± 2.18 years, p=0.046). Frequent reasons for missing doses were forgetfulness and inadequate medications. Participants with poor compliance had significantly reduced height velocity (HV) and HV standard deviation score (SDS) compared to those with good compliance (p<0.05). Conclusion: Poor compliance is more common in adolescents, those on longer duration of treatment and leads to significantly reduced height velocity. Regular monitoring throughout the course of rGH is important. Measures to improve compliance must address the underlying reasons.
Flodh H. Human growth hormone produced with recombinant DNA technology: Development and production. Acta Paediatr Scand. 1986;75(SUPPL. 325):1–9.
Ministry of Health Malaysia. The use of growth hormone in children and adults- Clinical Practice Guidelines. 2010;1–84. Available from: http://www.moh.gov.myhttp//www.acadmed.org.myhttp://www.endocrine.my/index.php
Haverkamp F, Johansson L, Dumas H, Langham S, Tauber M, Veimo D, et al. Observations of nonadherence to recombinant human growth hormone therapy in clinical practice. Clin Ther. 2008;30(2):307–16.
Kapoor RR, Burke SA, Sparrow SE, Hughes IA, Dunger DB, Ong KK, et al. Monitoring of concordance in growth hormone therapy. Arch Dis Child. 2008;93(2):147–8.
Lustig RH. Optimizing growth hormone efficacy: an evidence-based analysis. Horm Res. 2004;62 Suppl 3(suppl 3):93–7.
Graham S, Weinman J, Auyeung V. Identifying potentially modifiable factors associated with treatment non-adherence in paediatric growth hormone deficiency: A systematic review. Horm Res Paediatr. 2019;90(4):221–7.
Haverkamp F, Gasteyger C. A review of biopsychosocial strategies to prevent and overcome early-recognized poor adherence in growth hormone therapy of children. J Med Econ. 2011;14(4):448–57.
Ooi HL, Wu LL. Final height in growth-hormone-treated children with idiopathic growth hormone deficiency: The Malaysian Experience. Med J Malaysia. 2011;66(5):479–83.
Fisher BG, Acerini CL. Understanding the growth hormone therapy adherence paradigm: A systematic review. Horm Res Paediatr. 2013;79(4):189–96.
Cutfield WS, Derraik JGB, Gunn AJ, Reid K, Delany T, Robinson E, et al. Non-compliance with growth hormone treatment in children is common and impairs linear growth. PLoS One. 2011;6(1):5–7.
Hindmarsh PC, Brook CGD, Ministry of Health Malaysia, Matsui DM, Cutfield WS, Karagiannis G, et al. Optimizing growth hormone efficacy: an evidence-based analysis. PLoS One [Internet]. 2008;18(1):929–41. Available from: http://www.moh.gov.myhttp//www.acadmed.org.myhttp://www.endocrine.my/index.php
Lanes R. Long-term outcome of growth hormone therapy in children and adolescents. Treat Endocrinol. 2004;3(1):53–66.
Acerini C, Albanese A, Casey A, Denvir L, Jones J, Mathew V et al. Initiating growth hormone therapy for children and adolescents. Br J Nurs. 2012;Oct 11-24;21(18):1091-7.
Lass N, Reinehr T. Low treatment adherence in pubertal children treated with thyroxin or growth hormone. Horm Res Paediatr. 2015;84(4):240–7.
Rosenfeld RG, Bakker B. Compliance and persistence in pediatric and adult patients receiving growth hormone therapy. Endocr Pract. 2008;14(2):143–54.
Aydın BK, Aycan Z, Şıklar Z BM, Öcal G, Çetinkaya S et al. Adherence to growth hormone therapy: Results of a multicenter study. Endocr Pract. 2014;Jan;20(1):46–51.
Hartmann K, Ittner J, Müller-Rossberg E, Schönau E, Stephan R, Ullrich KP, et al. Growth hormone treatment adherence in prepubertal and pubertal children with different growth disorders. Horm Res Paediatr. 2013;80(1):1–5.
Van Dommelen P, Koledova E, Wit JM. Effect of adherence to growth hormone treatment on 0-2 year catch-up growth in children with growth hormone deficiency. PLoS One. 2018;13(10):1–12.
Arnao MDR, Sánchez AR, López ID, Fernández JR, De La Vega JAB, Fernández DY, et al. Adherence and long-term outcomes of growth hormone therapy with easypodTM in pediatric subjects: Spanish ecos study. Endocr Connect. 2019;8(9):1240–9.
Koledova E, Tornincasa V, Van Dommelen P. Analysis of real-world data on growth hormone therapy adherence using a connected injection device. BMC Med Inform Decis Mak. 2020;20(1):1–7.
Blanco-López A, Antillón-Ferreira C, Saavedra-Castillo E, Barrientos-Pérez M, Rivero-Escalante H, Flores-Caloca O, et al. Adherence to treatment in children with growth hormone deficiency, small for gestational age and Turner syndrome in Mexico: results of the EasypodTM connect observational study (ECOS). J Endocrinol Invest [Internet]. 2020;43(10):1447–52. Available from: https://doi.org/10.1007/s40618-020-01218-4
Smith SL, Hindmarsh PC BC. Compliance with growth hormone treatment – are they getting it? Arch Dis Child. 1995;73: 277.
Bagnasco F, Iorgi N Di, Roveda A, Gallizia A, Haupt R, Maghnie M. Prevalence and correlates of adherence in children and adolescents treated with growth hormone: A multicenter Italian study. Endocr Pract. 2017;23(8):929–41.
Matsui DM. Drug compliance in pediatrics: Clinical and research issues. Pediatr Clin North Am. 1997;44(1):1–14.
Hunter I, deVries C MA. Human growth hormone therapy: poor adherence equals poor growth. Arch Dis Child. 2000;82: A8.
Mohseni S, Heydari Z, Qorbani M, Radfar M. Adherence to growth hormone therapy in children and its potential barriers. J Pediatr Endocrinol Metab. 2018;31(1):13–20.
Friedman IM LI. Adolescents’ compliance with therapeutic regimens. Psychological and social aspects and intervention. J Adolesc Heal Care. 1987;8: 52–67.
Oyarzabal M, Aliaga M, Chueca M E, G UA. Multicentre survey on compliance with growth hormone therapy: what can be improved? Acta Paediatr. 1998;87: 387–39.
Wickramasuriya BPN, Casey A, Akhtar S Z, R, Ehtisham S, Barrett TG et al. Factors determining patient choice of device for GH therapy. Horm Res. 2006;65: 18–22.
Höybye C, Sävendahl L, Christesen HT, Lee P, Pedersen BT, Schlumpf M, et al. The NordiNet® International Outcome Study and NovoNet® ANSWER Program®: Rationale, design, and methodology of two international pharmacoepidemiological registry-based studies monitoring long-term clinical and safety outcomes of growth hormone therapy.Nor. Clin Epidemiol. 2013;5(1):119–27.
Stanhope R, Moyle L MM. Patient knowledge and compliance with growth hormone treatment.le. Arch Dis Child. 1993;68:525.
Miller BS, Velazquez E YK. Long-acting growth hormone preparations – current status and future considerations. J Clin Endocrinol Metab. 2020;105(6):e21:1–31.
Luo X, Hou L, Liang L, Dong G, Shen S, Zhao Z, et al. Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: Phase II and phase III multicenter, randomized studies. Eur J Endocrinol. 2017;177(2):195–205.
How to Cite
Copyright (c) 2022 Malaysian Journal of Paediatrics and Child Health
This work is licensed under a Creative Commons Attribution 4.0 International License.