What is the appropriate dosage and treatment approach for managing conditions related to Insulin-like Growth Factor 1 (IGF1) deficiency?

From the Guidelines

The appropriate treatment for IGF-1 deficiency primarily involves recombinant human IGF-1 (rhIGF-1), with a recommended starting dose of 0.04-0.08 mg/kg twice daily by subcutaneous injection, aiming to maintain IGF-1 levels within the normal range for age and sex 1.

Key Considerations

• Treatment should be administered shortly before or after a meal to reduce the risk of hypoglycemia, which is the most common side effect.
• Dosage adjustments should be made based on growth response and IGF-1 levels.
• Regular monitoring is essential, including IGF-1 levels every 3-6 months, growth velocity, bone age assessment annually, and screening for potential side effects such as hypoglycemia, tonsillar hypertrophy, and intracranial hypertension.
• In adults with GH insensitivity, dosing is typically 0.04-0.08 mg/kg once or twice daily, adjusted based on clinical response and side effects.

Monitoring and Follow-up

• Repeat monitoring of IGF1 at least twice yearly, dosing GH to keep IGF1 in physiologic range 1.
• Monitoring of head circumference at each visit, because GH treatment can cause abnormal growth of the head, especially if the fontanelles are open when GH is started 1.

Treatment Duration

• Treatment typically continues until growth plates close or desired height is achieved.
• Stopping GH treatment is recommended when epiphyseal closure is demonstrated, at the time of renal transplantation, or in patients with persistent severe secondary hyperparathyroidism, intracranial hypertension, or slipped capital femoral epiphysis 1.

From the FDA Drug Label

Therapy with OMNITROPE should be supervised by a physician who is experienced in the diagnosis and management of pediatric patients with short stature associated with GHD, Prader-Willi Syndrome (PWS), Turner Syndrome (TS), those who were born small for gestational age (SGA), Idiopathic Short Stature (ISS) and adult patients with either childhood onset or adult onset GHD.

Adult Growth Hormone Deficiency (GHD) Weight-Based Dosing Based on the weight-based dosing utilized in clinical studies with another somatropin product, the recommended dosage at the start of therapy is not more than 0. 04 mg/kg/week given as a daily subcutaneous injection. The dose may be increased at 4- to 8-week intervals according to individual patient requirements to not more than 0. 08 mg/kg/week. Clinical response, side effects, and determination of age- and gender-adjusted serum IGF-1 levels may be used as guidance in dose titration.

The appropriate dosage and treatment approach for managing conditions related to Insulin-like Growth Factor 1 (IGF1) deficiency is as follows:

• The dosage of somatropin should be individualized based on the growth response of each patient.
• For adult patients with Growth Hormone Deficiency (GHD), the recommended starting dosage is not more than 0.04 mg/kg/week given as a daily subcutaneous injection.
• The dose may be increased at 4- to 8-week intervals according to individual patient requirements to not more than 0.08 mg/kg/week.
• Clinical response, side effects, and determination of age- and gender-adjusted serum IGF-1 levels may be used as guidance in dose titration 2.

From the Research

IGF1 Deficiency Treatment Approach

• The appropriate dosage and treatment approach for managing conditions related to Insulin-like Growth Factor 1 (IGF1) deficiency involve the use of recombinant human IGF-1 (rhIGF-1) therapy 3, 4, 5.
• The efficacy of rhIGF-1 therapy in patients with severe primary IGF-I deficiency has been evaluated for more than two decades, with most patients achieving an adult height significantly greater than what would have been predicted in the absence of IGF-1 therapy 5.
• However, the growth response to rhIGF-1 therapy can be variable, and the clinical spectrum of primary IGF-I deficiency is widening to include many patients with a milder phenotype, creating a need for well-designed long-term clinical studies 5.

Combination Therapy with rhGH and rhIGF-1

• Combination therapy with recombinant human growth hormone (rhGH) and rhIGF-1 may provide better growth responses than rhIGF-1 monotherapy in prepubertal children with short stature and low IGF-I levels despite normal stimulated GH responses 3.
• The use of post-growth hormone receptor signaling agonists, which restore both GH signaling and IGF-I exposures, or the addition of long-acting rhGH species to rhIGF-1, may also be considered as alternative treatments for GHIS subjects 3.

Monitoring and Safety

• Treatment with rhGH increases IGF-1 levels, and monitoring both IGF-1 and growth constitutes an acceptable parameter of therapeutic safety and efficacy 6.
• Adverse events such as increased intracranial pressure and hypoglycemia are of therapeutic concern, and the incidence of adverse reactions should be closely monitored 4, 7.
• High-dose rhGH treatment for GHD is safe and can more effectively upregulate IGF-1, IGFBP-3, and GH, and promote the growth and development of children 7.

Factors Influencing Treatment Outcomes

• Sex, age, and diagnosis of GHD or ISS are major contributors to body composition parameters, such as fat percentage and muscle-to-fat ratio 6.
• Socioeconomic position and cumulative rhGH dose are not significant contributors to body composition parameters 6.
• IGF-1 levels are related to muscle mass but not to adiposity, and rhGH treatment aimed at increasing IGF-1 levels may alleviate the effects of increased adiposity by promoting muscle growth 6.