Human Growth Hormone Replacement Therapy
DESCRIPTION
Human growth hormone (GH) is synthesized in the anterior pituitary. GH binds to the surfaces of cells and stimulates the production of the insulin-like growth factor-I (IGF-l). IGF-I is responsible for many of the growth promoting effects attributed to GH. Recombinant GH (rhGH) is a category of pharmaceutical agents used to treat growth hormone deficiency (GHD).
Examples of preparations of recombinant human growth hormone are Genotropin®, Humatrope®, Norditropin®, Nutropin®, Saizen®, Serostim®, and Zorbtive™.
REFER TO DECISION SUPPORT TREE
POLICY
Recombinant human growth hormone therapy, for conditions related to proven GHD, growth failure, specific types of short stature, acquired immune deficiency (AIDS), short bowel syndrome, and the promotion of wound healing for burns is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Recombinant human growth hormone therapy for other conditions including but not limited to those unrelated to GHD, growth failure, and the promotion of wound healing for burns or AIDS is considered investigational.
MEDICAL APPROPRIATENESS
Recombinant human growth hormone therapy is considered medically appropriate if any of the following criteria are met:
Children or post pubescent children with proven GHD and growth failure as indicated by epiphyseal opening with x-ray evidence (See Additional Information for definition and discontinuation of therapy); or
Adults with proven GHD alone (See Additional Information for definition) or with any of the following conditions:
Multiple hormone deficiencies, such as hypopituitarism, as a result of hypothalamic or pituitary disease, radiation therapy, surgery, or trauma; or
Childhood onset that was not confirmed until adulthood by a negative response to standard growth hormone stimulation tests; or
Proven GHD with any of the following conditions:
Growth failure due to genetically confirmed Prader-Willi syndrome; or
Growth failure due to any of the following conditions:
Chronic renal insufficiency (i.e., renal insufficiency is defined as a glomerular filtration rate (GFR) less than 60ml/minute/1.73 meter squared) prior to renal transplantation; or
Short stature due to any of the following conditions:
Turner's syndrome (i.e., 45, XO genotype); or
SHOX (short stature homeobox-containing gene) deficiency when epiphyses are not closed; or
Idiopathic short stature, (i.e., non-growth hormone deficient short stature) with all of the following:
Height standard deviation less than -2.25; and
Growth rates that are unlikely to permit attainment of adult height in normal range; and
Epiphyses remain open; and
AIDS wasting or cachexia in adults with greater than 10% of baseline weight loss that cannot be explained by a concurrent illness other than HIV infection; and simultaneous treatment with antiviral agents; or
Short bowel syndrome in individuals receiving specialized nutritional support when used in conjunction with optimal management of short bowel syndrome; or
Wound healing for burns.
Human growth hormone is considered not medically appropriate for, but not limited to, the following conditions:
AIDS in children
Anabolic therapy to enhance body mass or strength
Athletic performance enhancement
Constitutional delay of growth and development, which is lower than expected height percentiles compared with the target height percentiles and delayed skeletal maturation when growth velocities and rates of bone age advancement are normal
Crohn's Disease
Cystic fibrosis
Diabetic foot ulcer
Down syndrome and other syndromes associated with short stature and malignant diathesis
Dwarfism other than SHOX deficiency
Gastrointestinal hemorrhage
Glucocorticoid-induced growth failure
Growth retardation with juvenile idiopathic arthritis
Hand-Schuller Christian Disease
Hyperinsulinism
Idiopathic dilated cardiomyopathy
Infertility
Inflammatory bowel disease, short gut syndrome
Kwashiorkor
Obesity
Osteogenesis imperfecta
Osteoporosis
Sepsis
Short stature post-renal transplantation
Skeletal dysplasias
Somatopause (older adults)
Testing or any other treatment of the geriatric and/or adult of normal stature as denoted by fused growth (epiphyseal) plates
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (e.g., AHFS Drug Information, USP DI Drug Information for the Health Care Professional) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., Drug Information for the Health Care Professional: USP-DI).
Proven growth hormone deficiency for children is determined by failure of two growth hormone stimulation tests. A failure is generally defined as a peak serum growth hormone value of less than 10 mcg/L after GH stimulation.
Proven growth hormone deficiency for adults is determined by failure of the insulin tolerance test with an insulin-induced hypoglycemia value less than 5 µg/L (micrograms/liter). This test is contraindicated for individuals with seizure disorders or coronary artery disease. A provocation test using arginine and hypothalamic-releasing hormone for GH (GHRH) is the alternative for those individuals. An abnormal response is a value less than 5 µg/L (micrograms/liter).
Examples of growth hormone stimulation tests are L-dopa, clonidine, glucagon, propranolol, arginine, or insulin.
In children, GH therapy is typically discontinued when the growth velocity is less that 2 cm per year, when epiphyseal fusion has occurred, or when the height reaches the 5th percentile of adult height.
There is insufficient evidence supporting the use of human growth hormone therapy for other conditions / diseases.
Human growth hormone replacement therapy, for other conditions including but not limited to those unrelated to proven GHD, growth failure, the promotion of wound healing for burns and AIDS does not meet the following technology evaluation criteria:
The technology must have final approval from the appropriate government regulatory bodies.
The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.
The technology must improve the net health outcomes.
The technology must be as beneficial as any established alternatives.
The improvement must be attainable outside the investigational settings.
SOURCES
Attanasio, A., Attie, K., Baxter, R., Bengtsson, B. A., Black, A., Blethen, S., et al., (1998). Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: Summary statement of the growth hormone research society workshop on adult growth hormone deficiency. Journal of Clinical Endocrinology and Metabolism, 83 (2), 379-381.
Attie, K. M., Bengtsson, B. A., Blethen, S. L., Blum, W., Cameron, F., Carel, J. C., et al., (2000). Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: Summary statement of the GH Research Society. Journal of Clinical Endocrinology & Metabolism, 85 (11), 3990 - 3993.
BlueCross BlueShield Association, Medical Policy Reference Manual. (4:2006). Human Growth Hormone (5.01.06). Retrieved January 24, 2007 from BlueWeb.
Gharib, H. (2003). American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children - 2003 update. Endocrine Practice, 9 (1), 65-76.
MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2006). Somatropin. Retrieved January 11, 2007 from MICROMEDEX Healthcare Series.
MICROMEDEX Healthcare Series. UPS DI Drug Information for the Healthcare Professional. (2005). Growth hormone (systemic). Retrieved January 10, 2007 from MICROMEDEX Healthcare Series.
Novo Nordisk. (2006). Product information. Norditropin cartridges. Retrieved January 12, 2007 from http://www.norditropin-us.com/tools/norditropin_prescribing_information.pdf.
Stevens, L. A., Coresh, J., Greene, T., & Levey, A. S. (2006). Assessing kidney function - Measured and estimated glomerular filtration rate. The New England Journal of Medicine, 354 (23), 2473-2483.
The Technology Evaluation Center. (1996, July). Growth Hormone Guidelines. (Vol. 13, No7). Chicago: BlueCross BlueShield Association.
The Technology Evaluation Center. (1996, September). Recombinant Human Growth Hormone Replacement Therapy in Adults. (Vol. 11, No. 9). Chicago: BlueCross BlueShield Association.
The Technology Evaluation Center. (1996, September). Recombinant Human Growth Hormone Therapy in Catabolic Illness. (Vol. 11, No.10). Chicago: BlueCross BlueShield Association.
The Technology Evaluation Center. (2001, November). Recombinant Human Growth Hormone (GH) Therapy in Adults with Age-Related GH Deficiency. (Vol. 16 No.11). Chicago: BlueCross BlueShield Association.
U. S. Food and Drug Administration. (2003, November). Center for Devices and Radiological Health. Product label: Zorbtive™. Retrieved July 26, 2005 from http://www.fda.gov/cder/foi/label/2003/20604s026_zorbtive_lbl.pdf.
U. S. Food and Drug Administration. (2004, August). Center for Devices and Radiological Health. Product label: Saizen®. Retrieved January 12, 2007 from http://www.fda.gov/cder/foi/label/2004/19764s020lbl.pdf.
U. S. Food and Drug Administration. (2005, November). Center for Devices and Radiological Health. Product label: Nutropin®. Retrieved January 12, 2007 from http://www.fda.gov/cder/foi/label/2006/019676s026lbl.pdf.
U. S. Food and Drug Administration. (2006, April). Center for Devices and Radiological Health. Product label: Genotropin®. Retrieved January 10, 2007 from http://www.fda.gov/cder/foi/label/2006/020280s049lbl.pdf.
U. S. Food and Drug Administration. (2006, October). Center for Devices and Radiological Health. Product label: Humatrope®. Retrieved January 9, 2007 from http://www.fda.gov/cder/foi/label/2006/019640s058lbl.pdf.
U. S. Food and Drug Administration. (2006, October). Center for Devices and Radiological Health. Product label: Serostim®. Retrieved January 10, 2007 from http://www.fda.gov/cder/foi/label/2006/020604s035lbl.pdf.
U. S. Food and Drug Administration. (2007, January). Center for Devices and Radiological Health. Cumulative list of orphan designated products. Retrieved January 24, 2007 from http://www.fda.gov/orphan/designat/alldes.rtf.
Wilson, T. A., Rose, S. R., Cohen, P., Rogol, A. D., Backeljauw, P., Brown, R., et al. (2003). Update of guidelines for the use of growth hormone in children: The Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutic Committee. The Journal of Pediatrics, 143 (4), 415-421.
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EFFECTIVE DATE |
6/9/2007 |
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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
Pharmaceutical Decision Support Tree
Recombinant Human Growth Hormone (Genotropin®, Humatrope®, Norditropin®, Nutropin®, Saizen®, Serostim®, and Zorbtive™)
Most contracts/benefit plans contain limitations regarding human growth hormones. Please refer to any applicable benefit plan exclusions/limitations prior to beginning the questions below.
Is the requested medication being used to treat any of the following conditions?
AIDS in children
Anabolic therapy to enhance body mass or strength
Athletic performance enhancement
Constitutional delay of growth and development, which is lower than expected height percentiles compared with the target height percentiles and delayed skeletal maturation when growth velocities and rates of bone age advancement are normal
Crohn's Disease
Cystic fibrosis
Diabetic foot ulcer
Down syndrome and other syndromes associated with short stature and malignant diathesis
Dwarfism other than SHOX (short stature homeobox-containing gene) deficiency
Gastrointestinal hemorrhage
Glucocorticoid-induced growth failure
Growth retardation with juvenile idiopathic arthritis
Hand-Schuller Christian Disease
Hyperinsulinism
Idiopathic dilated cardiomyopathy
Infertility
Inflammatory bowel disease, short gut syndrome
Kwashiorkor
Obesity
Osteogenesis imperfecta
Osteoporosis
Sepsis
Short stature post-renal transplantation
Skeletal dysplasias
Somatopause (older adults)
If yes, this does not meet medical necessity and / or medical appropriateness criteria
If no, go to question #2
Is the individual a child, under the age of 18, with proven growth hormone deficiency indicated by the following?
Failure of two growth hormone stimulation tests, which is generally defined as a peak serum growth hormone value of less than 10mcg/L after growth hormone stimulation
If yes, go to question #3
If no, go to question #4
Does the child, under the age of 18, have growth failure indicated by epiphyseal opening with x-ray?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the individual an adult, 18 year or older, with proven growth hormone deficiency indicated by the following?
Failure of the insulin tolerance test with an insulin-induced hypoglycemia value less than 5 µg/L (micrograms/liter)
OR if contraindicated because of seizure disorders or coronary artery disease
Failure of a provocation test using arginine and hypothalamic-releasing hormone for GH (GHRH) with a value less than 5 µg/L (micrograms/liter)
If yes, go to question #5
If no, go to question #7
Does the adult, 18 year or older, have proven growth hormone deficiency alone or with any of the following conditions?
Multiple hormone deficiencies, such as hypopituitarism, as a result of hypothalamic or pituitary disease, radiation therapy, surgery, or trauma; or
Childhood onset that was not confirmed until adulthood; or
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Does the individual have proven growth hormone deficiency due to any of the following conditions?
Growth failure with genetically confirmed Prader-Willi syndrome; or
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Does the individual have growth failure due to any of the following conditions?
Chronic renal insufficiency (i.e., renal insufficiency is defined as a glomerular filtration rate (GFR) less than 60ml/minute/1.73 meter squared) prior to renal transplantation; or
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #8
Does the individual have short stature due to any of the following conditions?
Turner's syndrome (i.e., 45, XO genotype); or
SHOX deficiency when epiphyses are not closed; or
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #9
Does the individual have any of the following conditions?
AIDS wasting or cachexia with greater than 10% of baseline weight loss that cannot be explained by a concurrent illness other than HIV infection and simultaneous treatment with antiviral agents; or
Short bowel syndrome and receive specialized nutritional support used in conjunction with optimal management of short bowel syndrome; or
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
This document has been classified as public information.