Growth hormone: is it a personal choice medication or medical necessity in patients with PWS?

Luis Emilio 5th birthday party!

Luis Emilio's Father (Hjalmar) I hope he gave the toy back!

The good news:  Luis Emilio’s growth hormone (GH) will no longer be paid out of pocket!! This has the whole family very happy.

To be fair:  I want to clarify that by no means did I mean to single out  Aetna health insurance, they just happen to be the first on a list of health insurances that were in alphabetical order. Another important point is that by no means is this a complete and thorough review of the evidence available.

My concern:
GH is the only drug approved by the U.S. Food & Drug Administration (FDA) for the treatment of Prader-Willi syndrome. I thought that if Luis Emilio can now get his medication for free in Nicaragua, patients in the USA are probably having their GH covered by their insurance as well. I looked at the Aetna 2011 Preferred drug pocket guide for Emory members and found that GH is a Tier 4  (personal choice) medication.  This insurance company technically covers the mediation. The patient will have to pay $100 co-pay though.

The same guide also states “Emory’s plan goal is to help keep the cost of prescription drugs affordable and provide you with access to the medications you need to stay healthy.” This brings up a lot of questions. Is $100 dollars affordable for most families? What makes a medication a personal choice? The most important question is:  Does the evidence show that growth hormone treatment (GHT) is needed in patients with PWS to stay healthy?

Lets look at some of the evidence:

We know the best evidence will be from randomized controlled trials (RCT).  One randomized study of twenty-five children with PWS, ages 4-37 months; found that the group that received GHT had: ¹

1. Increased Height
2. Improved language skills
3. Improved cognitive skills
4. Decrease body fat
5. Improved motor ability
6. One PWS subject experienced scoliosis progression.

If you are wondering about scoliosis and GHT, a RCT  found that GH treated children had similar onset of scoliosis and curve progression as randomized controls. ²

Another benefit of GHT found in a randomized, controlled GH trial in infants and prepubertal children (n=85) was:  ³

1. Improved HDLc/LDLc ratio. (Cholesterol)

GHT has also been studied in adults with PWS.  Forty-six adults with PWS were randomized to GHT or placebo treatment for 12 months in a double-blind trial and found that the group that received the GHT had:⁴

1. Decrease in visceral fat mass
2. Decreased abdominal fat mass
3. Decreased thigh fat mass
4. Increase muscle mass
5. Lean body mass improved
6. Total fat mass decreased
7. No major side effects were seen.

Not all studies that have been done on GHT in individuals with PWS are RCT. The results of these other studies add to the body of evidence in different ways:

1. They show consistency in the results. “Study findings that are replicated in different populations and by different investigators carry more weight than those that are not.” ⁵

Researchers compared 21 children (6-9 years old) treated with hGH for 6 years with 27 children of similar ages (5-9 years old) prior to treatment with hGH.  They found that PWS children treated with hGH demonstrated:⁶

1. Decreased body fat
2. Increased height
3. Greater motor strength
4. Increased high-density lipoprotein (good cholesterol)
5. Decreased low-density lipoprotein (bad cholesterol)

2. A study that followed 20 patient with PWS that received GHT proved a dose response: “The cumulative dose of rhGH over 10 years correlated inversely with the total body fat percentage” ⁷

Other concerns:

There have been concerns about Sleep disorders in patients treated with GH. One case report showed Obstructive sleep Apnea (OSA) developed after 6 months of treatment and resolved after stopping GH.⁸ Like I’ve mentioned in other post though, case reports are at the bottom of the list when it comes to quality of evidence.

 One study that looked at sleep disorders before starting GHT and 6 weeks after starting GHT found no significant changes in sleep-related disorders before and after starting GHT.  It would have been nice if this study would have been longer. In the case report it took 6 months before she developed OSA! 12 infants did have an increase in the frequency of obstructive events associated with either upper respiratory infections or a diagnosis of gastroesophageal reflux after starting GHT. After the upper respiratory infection or GERD resolved so did the increase in frequency of obstructive events. ⁹ 

Current available information argues against a cause and effect relationship between rhGH treatment and increase mortality. Dr. Phillip D.K. Lee reviews the evidence in regards to this relationship in detail and can be found at the web site:  http://www.gghjournal.com/volume22/2/featureArticle.cfm

My thoughts:

I don't know how health insurance companies determine if a medication is a "personal choice" and classify it as a higher tier. With out an alternative treatment available, I don't think this policy is helping their goal of keeping prescription drugs affordable for their clients. Based on the evidence available I think GHT is a medical necessity for patients with PWS. The benefits go beyond increased height.  Hjamar (Luis Emilio's father) can confirm how I pushed for GHT to be started for Luis Emilio.   It wasn't an easy task. I had to convince my family that the health benefits were greater then the risk; and that the benefits were worth the $300- $400 a week they had to pay out of pocket when he started therapy. 

I understand the insurance companies have to make these same decisions on a larger scale. They may feel that even though GHT  increases height, reduces body fat, improves language, motor and cognitive skills; patient's with out GHT are not at risk of becoming acutely ill or having a life threatening condition if they don't start treatment. Since lack of treatment does not put patients at risk of harm, it may be a personal choice to start treatment. 

If they can't afford it, it is not a personal choice all patients with PWS can make. Luis Emilio did have periods where GHT was discontinued because the medication was too expensive.

Bibliography: 
1. Myers SE, Whitman BY, Carrel AL, Moerchen V, Bekx MT, Allen DB. Two years of growth hormone therapy in young children with Prader-Willi syndrome: physical and neurodevelopmental benefits. Am J Med Genet A. 2007 Mar 1;143(5):443-8. PubMed PMID: 17103437.
2. de Lind van Wijngaarden RF, de Klerk LW, Festen DA, Duivenvoorden HJ, Otten BJ, Hokken-Koelega AC. Randomized controlled trial to investigate the effects of  growth hormone treatment on scoliosis in children with Prader-Willi syndrome. J Clin Endocrinol Metab. 2009 Apr;94(4):1274-80. Epub 2009 Jan 21. PubMed PMID: 19158197.
3. de Lind van Wijngaarden RF, Cianflone K, Gao Y, Leunissen RW, Hokken-Koelega AC. Cardiovascular and metabolic risk profile and acylation-stimulating protein levels in children with Prader-Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab. 2010 Apr;95(4):1758-66. Epub 2010 Feb 19. PubMed PMID: 20173020.
4. Sode-Carlsen R, Farholt S, Rabben KF, Bollerslev J, Schreiner T, Jurik AG, Christiansen JS, Höybye C. One year of growth hormone treatment in adults with Prader-Willi syndrome improves body composition: results from a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2010 Nov;95(11):4943-50. Epub  2010 Aug 11. PubMed PMID: 20702523.
5. Gordis, Leon. (2009). Epidemiology, fourth edition. Philadelphia, PA: Saunders Elsevier.
6. Carrel AL, Myers SE, Whitman BY, Eickhoff J, Allen DB. Long-term growth hormone therapy changes the natural history of body composition and motor function in children with prader-willi syndrome. J Clin Endocrinol Metab. 2010 Mar;95(3):1131-6. Epub 2010 Jan 8. PubMed PMID: 20061431; PubMed Central PMCID: PMC2841537.
7. Sipilä I, Sintonen H, Hietanen H, Apajasalo M, Alanne S, Viita AM, Leinonen E. Long-term effects of growth hormone therapy on patients with Prader-Willi syndrome. Acta Paediatr. 2010 Nov;99(11):1712-8. doi: 10.1111/j.1651-2227.2010.01904.x. Epub 2010 Jul 5. PubMed PMID: 20545932.
8. Nixon GM, Rodda CP, Davey MJ. Longitudinal association between growth hormone  therapy and obstructive sleep apnea in a child with Prader-Willi syndrome. J Clin Endocrinol Metab. 2011 Jan;96(1):29-33. Epub 2010 Oct 13. PubMed PMID: 20943780.
9. Miller JL, Shuster J, Theriaque D, Driscoll DJ, Wagner M. Sleep disordered breathing in infants with Prader-Willi syndrome during the first 6 weeks of growth hormone therapy: a pilot study. J Clin Sleep Med. 2009 Oct 15;5(5):448-53. PubMed PMID: 19961030; PubMed Central PMCID: PMC2762717.