Adherence in growth hormone therapy & approach to improve it!!

1. ABDULMOEIN AL-AGHA, MBBS,DCH, FRCPH)UK(
PROFESSOR & PEDIATRIC ENDOCRINOLOGIST
AAGHA@KAU.EDU.SA
Adherence to GH therapy & approaches to
improve !!

2. Overview
• Introduction to GH therapy.
• Challenges of GH therapy.
• Factors of poor response to GH treatment.
• Factors contributing to non adherence to GH therapy.
• Strategies to improve GH treatment adherence.
• Easy use of GH devices.
• Near -Future long acting once weekly GH therapy.

3. GH therapy
• The treatment for children with growth hormone
deficiency has significantly developed since its first uses
from human cadavers (1958), until the arrival of
recombinant human growth hormone (1985).
• The biotechnological advance has allowed an expansion in
its uses due to a greater availability, as well as a greater
biological safety.
• Recombinant GH, is used for treatment of several
conditions including:
– GHD, Turner’s syndrome, idiopathic short stature, SGA, PWS,
CRF & Noonan’s syndrome …….. etc.

4. Targets of GH Therapy
Albertson Wikland, Horm Res 2012

5. Effects of GH Therapy in Children

6. GH Therapy
• The recommended GH dose is calculated based on
body weight & vary according to specific condition (i.e.
dose of GHD is different from that of CRF or ISS).
• In case of GHD, treatment with GH should be initiated
early & be monitored by a pediatric endocrinologist
every 3–6 months in order to:
– verify growth velocity.
– identify possible side effects.
– titrating the GH dose by measuring IGF-1 & using prediction
modules !!).
– Checking for patients compliance (adherence).

7. Challenges in GH Therapy
WHY OTHER
CHILDREN
MUCH TALLER
THAN ME?

8. • Growth hormone deficiency (GHD) is one of the most
important endocrine treatable causes of short stature.
• Variability in response to treatment from one child to
another has been observed in the clinical practice &
documented in many studies due to several endogenous
& exogenous factors.

9. Factors influencing the response to GH?
• Indication of GH therapy ( GH Deficiency, Turner Syndrome, SGA…).
• Age of starting GH therapy.
• Pubertal status.
• GH dose.
• GH dose titration 3-6 monthly.
• Treatment adherence.
• Birth Weight (SGA).
• Concomitant medication.
• Associated co-morbidity.
• Rarely, development of GH antibodies.
• Cultural believes (spreading not true side effects)
• Family education and uncertain worries on side effects
• Limited parents information on GH therapy.

10. • Optimization of GH therapy is a prime challenge in the
treatment of GHD.
• It requires evaluation of the response of an individual to the
therapy.
• To analyze or predict the probable amount of growth that can
be expected during treatment, researchers have developed
prediction models.
• The second important challenge which limits the effectiveness
of GH therapy is patient adherence.
• A literature search has found several studies which identified
that poor adherence is the major factor that reduces the
effectiveness of GH therapy

11. The existence of non-responder phenotypes,
commonly due to lack of therapeutic compliance,
can pose severe limitations regarding effectiveness,
with the corresponding economic impact for Health
System.

13. Non Adherence
• Non adherence rates in the setting of long-term medication
regimens average only 50%.
• Poor adherence has an impact on:
– Suboptimal growth response
– Affecting growth outcome (final adult height not reached
the target height)
– Future health (osteoporosis, abdominal obesity, premature
atherosclerosis ….)
– Economic consequences
Al Herbish AS, et al. Expert Rev Endocrinol Metab 2014; 9:319–325.

14. Significant proportion of patients are poor
responders

15. Factors associated with GH poor Adherence
• Daily subcutaneous injection.
• Long-term treatment (for many years).
• Complexity of treatment device.
• Age: usually young age groups (reject needles) or
adolescents (rejects everything in life!!).
• Individual & family dynamics.
• Patient or family's understanding of treatment benefits &
consequences of non-adherence.
• Expensive therapy: the annual cost for a 30 kg child has been
estimated as US$ 15,000 to US$ 20,000 per annum.
• Cultural false believes on GH side effects.

16. Adherence to GH Therapy
• Poor adherence to GH therapy is more common than we think !!

17. Solutions

18. Strategies
• As no method can directly assess the adherence to
GH treatment, the simplest & most efficacious
means of detecting the real degree of adherence is
to regularly interview the patients.
• However, a single intervention is not sufficient, but
several strategies should be available to reduce
issues contributing to poor adherence.

19. Suggestions for the management of non-adherence in
GHD children treated with GH
• Non-aggressively interview the patient & his/her family
in order to assess the adherence status.
• Discuss the reasons for non-adherence.
• To encourage patients & caregivers awareness
campaigns and educational programs (deficient in our
community).
• If needed, change the device (Ease use devices).
• Educational intervention & motivational support.
• Long - Acting Growth hormone products.

20. Education & Motivation
• Educational interventions that explain the
importance of GH treatment & final outcomes are
considered very useful to the patient &family.
• Appropriate motivational support is essential to
ensure that the child’s & parents’ commitment to
GH treatment does not diminish over time.

21. GH Device
• Recent evaluations of patient, caregiver and healthcare
professional preferences for growth hormone administration
devices have indicated that the most important attributes for
such devices include:
– ease of use
– Reliability
– lack of pain during injection
– safety
– easy steps for preparation & administration of growth hormone.

22. Electronic autoinjector device
• In 2007, an electronic autoinjector device (easypod™, Merck Serono S.A.,
Geneva, Switzerland) was introduced for the administration of rhGH
(Saizen®, Merck Serono S.A.)
• Easypod is a hidden-needle autoinjector device that records:
– date & time of injection.
– prescribed dose (mg)
– injected dose (mg) and injection status (dose setting, performed, missed or partial
injection).
• Owing to the electronic registration of each rhGH injection, patient
adherence can be monitored accurately.
• The device has been well accepted by patients, with 98% of survey
respondents in one study reporting a ‘good' or ‘very good' overall impression
of this device and 90% of children in another study wanting to continue
using the device.
Journal of Endocrinological Investigation (2019) 42:1241–1244

23. Easypod™, Merck Serono S.A., Geneva, Switzerland

24. Genotropin® GoQuick®: Pre-set dosing
 Allows the correct dose to be given
every time
 Gives patients reassurance that the correct dose
is being administered, regardless of who is
injecting
 Gives prescriber confidence that the correct dose
is given every time, regardless of who is injecting
 No daily dose setting reduces injection time and
minimises mistakes

25. Genotropin® GoQuick®: Available in two doses
• GoQuick is available in two doses and comes in two
different colours to represent the different doses:
• Helps to ensure patients can quickly identify and check
they have been dispensed the correct dose
• All GoQuick Pens are prepared and used in the same way
BLUE:
5.3 mg somatropin
PURPLE:
12 mg somatropin

26. Once-Weekly Administration of Sustained-Release
Growth
• Available rhGH products require subcutaneous injection 6 - 7
times a week for the entire treatment period, which may
reduce the treatment compliance.
• With the progress in molecular biotechnology, enabling large-
scale production of recombinant human growth hormone
(rhGH).
• TransCon™ Growth Hormone “Ascendis Pharma” in the
treatment of Pediatric Growth Hormone Deficiency: Results of
the Phase 3 height Trial (expected to go for FDA approval in
April 2020).

27. Ascendis Pharma Announces Once-weekly TransCon™ Growth Hormone
Demonstrated Superiority on Primary Endpoint Compared to a Daily
Growth Hormone in Phase 3 heiGHt Trial for Pediatric Growth Hormone
Deficiency
• The trial met its primary objective, demonstrating that TransCon hGH
was observed to be non-inferior and, additionally, superior to the daily
hGH on the primary endpoint of annualized height velocity (AHV) at 52
weeks
• March 04, 2019 06:30 ET | Source: Ascendis Pharma A/S

28. Conclusions
• GH therapy requires daily injections over many years and
compliance can be difficult to sustain.
• As growth hormone (GH) is expensive, non-compliance is
likely to lead to suboptimal growth, at considerable cost.
• Non-compliance with GH treatment is common, and
associated with reduced linear growth.
• Non-compliance should be considered in all patients
with apparently suboptimal response to GH treatment.

29. Conclusions
• Patients and parents should be actively encouraged and
educated to carefully adhere to prescribed therapeutic
procedures to avoid short final stature.
• Encourage patients & caregivers awareness campaigns
and educational programs.
• Important to select easy method of GH delivery.
• Educational intervention & motivational support.
• Long - Acting Growth hormone products (once weekly
injection) is coming in near future ‫ﷲ‬ ‫ﺷﺎء‬ ‫ان‬ , which is
hopefully will improve GH adherence.

30. Thanks