A time to grow: practical strategies for navigating dynamic patient and parent preferences in an evolving pediatric growth hormone deficiency treatment landscape

Introduction

It is estimated that 1 in 4,000 to 10,000 children worldwide have growth hormone deficiency (GHD)^1,2, a rare condition that occurs when the anterior pituitary gland doesn’t produce enough growth hormone. GHD is most commonly associated with short stature and delayed skeletal maturation in children, and may also cause muscle, skeletal, and metabolic abnormalities, psychosocial challenges, cognitive deficiencies, and reduced quality of life.^3-5 GHD can result from genetic causes, brain abnormalities, traumatic head injuries, or damage to the pituitary gland, but can also occur spontaneously for an unknown cause.^6-7

For decades, daily injections of synthetic growth hormone (somatropin) were the standard of care for pediatric GHD. However, the data point to low patient adherence with daily somatropin injections and to resulting suboptimal growth outcomes.^8,9 More recently, long-acting growth hormone (LAGH) formulations, which require less frequent injections, have been introduced. These formulations provide greater convenience compared with daily injections and may help improve adherence and outcomes.⁹

Because many children with GHD begin treatment at a young age, the treatment choice is often made by parents. As children mature, they may want to have a more active and vocal role in decisions regarding their own care. Additionally, family dynamics and daily routines may evolve as families grow and children become more independent. For children who began treatment on a daily somatropin regimen, a variety of factors may lead them and their parents to consider transitioning to a LAGH formulation.

Candid conversation is essential for optimizing GHD treatment as children mature

Although the first LAGH received FDA approval for the treatment of pediatric GHD in 2021, about 85% of my patients still use a daily somatropin regimen. In discussing a potential switch to a LAGH formulation with patients and their families, I’ve learned that there is no “one-size-fits-all” approach. Helping patients and their parents select a regimen most likely to achieve desired growth trajectories requires discerning and working within the confines of parents’ perspectives on what is best for their children while also respecting and considering the child’s preferences. Oftentimes this may be a bit of a balancing act, especially as children mature and begin establishing their independence.

Many of my patients begin treatment when they are in elementary school, a time when a daily regimen is more readily incorporated into families’ daily routines. However, for children who are afraid of needles or experience more than minimal injection site pain, this regimen can become a source of daily conflict and anxiety. In these cases, switching to a LAGH formulation provides a simple yet effective way to reduce injection frequency and associated familial stress while ensuring that the child receives the GH dose they need to maintain their target growth trajectories. I find this may be the case in busy households in which both parents work and/or in which there are multiple children on different schedules, both of which may lead to missed doses. In these settings, a LAGH formulation can provide 2 benefits. First, it can simplify the family’s overall schedule by requiring 1 injection each week rather than 7 injections. Secondly, the slower release of GH in the LAGH formulation may allow for flexibility if a dose is administered a day late.

A key strategy to ensuring continued adherence to a treatment regimen—whether daily or weekly—is to maintain the conversation around treatment choices as children get older. In my practice, I’ve learned that patient and family attitudes and preferences regarding therapy evolve as children enter middle school. At this age (usually around 12 to 13 years), there are several factors that can drive a change in regimen. These include patients’ increasing independence and ability/desire to be more engaged in their own health care; busier schedules that may make daily dosing more challenging; and more opportunities for patients to be away from home (sleepovers at friends’ houses, summer camp, school trips, etc). With respect to the former, children at this age are becoming better able to administer injections to themselves. In the latter instances, daily dosing may not be practical if refrigeration isn’t readily available/accessible or if children have concerns about sharing their disease status or injecting themselves in front of others.

In my practice, many patients at this age want to take control of their health care and may advocate for switching to a LAGH formulation that simplifies their treatment regimen and reduces the need for injections in settings outside their homes. Sometimes this change is made with the support and encouragement of parents, but sometimes adolescent and parent views and desires are not entirely aligned. I’ve also observed that parents may support such a switch in theory, but are constrained by the realities of their insurance coverage. In these cases, I strive to promote the patient’s choice (assuming I agree with it from a medical perspective) while being respectful of parents’ concerns and the limits of coverage. I also direct families to relevant patient assistance programs when insurance coverage is a limiting factor in switching to a LAGH formulation regimen.

Assessing therapeutic efficacy

Whether daily or long-acting, GH replacement therapy is effective only when patients adhere to their chosen regimen. Periodic assessment of endogenous GH levels is routinely used to monitor treatment adherence in pediatric GHD. This is done by measuring levels of insulin-like growth factor 1 (IGF-1), which is a surrogate marker for GH activity.¹⁰

This testing is typically performed every 3 to 4 months, and, in my practice, I typically check every other visit. With daily GH, levels can be checked at any time and are done during a routine office visit. However with LAGH, ideally it is best to check 4 to 4.5 days after injection to assess the average IGF-1 level. There is a “corrective” factor for each LAGH that can be used to adjust test results performed outside the 4 to 4.5 day window. However, this is less than ideal and, in some cases, may result in patients having IGF-1 levels checked outside the clinic visit at their local laboratory. This can add burden to patients’ (and their parents’) schedules.

Balancing near-term preferences with long-term growth outcomes

In my experience, the most effective way to ensure adherence to a GH replacement therapy regimen is to help children and their parents understand how near-term treatment choices and actions impact long-term growth outcomes. The reality is that the most effective treatment option is the one to which patients are most likely to adhere. A LAGH formulation that is injected less frequently and improves treatment convenience may improve adherence and outcomes.⁹ In treatment-naïve patients and those who switched from a daily GH formulation, the LAGH called Skytrofa, which is administered with an autoinjector, has been shown to provide growth benefits compared with LAGH formulations administered by pen or syringe.^11-13

Safety is another important factor in selecting and adhering to a given treatment regimen. In discussions of switching from a daily to a LAGH formulation, patients and parents often have more questions about safety than they do about efficacy. A growing body of clinical evidence demonstrates that the autoinjector LAGH formulation and daily somatropin formulations have comparable safety.^12-14 Sharing safety and efficacy data of all therapeutic options are essential for informed decision-making. It’s been my experience that adherence is better when patients and their parents understand and are comfortable with the near- and long-term risk and benefits of whichever regimen they choose.

Treatment duration is the final step in an evolving care journey

Identifying if and when GH replacement therapy is no longer needed is a critical component in patients’ evolving treatment needs and optimizing their long-term health. Treatment is usually ended when growth velocity decelerates to less than 2 cm per year and the patient’s bone age is more than 16 years (boys) and 14 to 15 (girls).¹⁵ However, it is important to determine if patients produce sufficient GH to meet adult needs or if they meet the criteria for a diagnosis of adult GHD.¹⁰ Many patients have normal GH levels once they attain late adolescence, but identifying those who don’t and who may require continued GH replacement therapy is essential.¹⁵ Accurate assessment of endogenous GH levels can be done once the patient has discontinued GH replacement therapy for 1 to 3 months.¹⁵

In my experience, many patients are unaware of the important role that GH plays in a variety of physiologic systems beyond linear bone growth and may not appreciate the important benefits that GH treatment can provide throughout life. Adults with GHD have an increased likelihood of experiencing comorbidities and complications, including metabolic syndrome, osteoporosis, muscle wasting, and fatigue and have increased cardiovascular risk and decreased quality of life. Adult GHD also is associated with economic burdens due to increased health care utilization, loss of productivity, and burdens associated with disease-related comorbidities.^16,17 This underscores the importance of helping affected patients of all ages achieve a healthy future.

Conclusions

The evolving pediatric GHD landscape provides opportunities and challenges for patients and their parents. Clinicians can best help these patients achieve optimal treatment outcomes by remaining up to date on the latest clinical evidence regarding treatment options and helping patients and parents choose a regimen to which they can adhere. Revisiting treatment choices as family dynamics change and pediatric patients mature and take greater control of their health care is important for maintaining adherence. Periodic assessment of IGF-1 is a useful tool for identifying potential issues around adherence and optimizing treatment. Managing care for minors can be challenging if patient and parent preferences are not fully aligned or if insurance coverage is an issue. Keeping the patient’s long-term health outcomes at the center of conversation and helping families make data-driven decisions is how I turn these challenges into win-win opportunities.

References

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