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IGFD Classifications

IGFD is classified based on cause of deficiency in serum IGF-1 and GH levels.

Treatment with Increlex®

Discover more about treatment with Increlex® in children with severe Primary IGFD

IGF-1 Significance Is Growing

Growth Hormone (GH) Deficiency (GHD) and Insulin-Like Growth Factor-1 (IGF-1) Deficiency (IGFD) are two distinct hormone disorders.22

Any growth disorder caused by impaired GH secretion is classified as GHD.10 IGFD classifications are based on cause of deficiency and all include low levels of IGF-1:

  • Secondary IGFD: IGF-1 levels are low and may be due to GH deficiency, malnutrition, hypothyroidism or other factors1
  • Primary IGFD: IGF-1 levels are low, even though growth hormone levels are normal or even high6
  • Severe Primary IGFD: a type of Primary IGFD in which IGF-1 levels are exceptionally low, despite sufficient or high growth hormone levels1,17

Severe Primary IGFD is specifically defined as1:

  • Height standard deviation score = -3.0 and
  • Basal IGF-1 standard deviation score = -3.0 and
  • Normal or elevated growth hormone (GH)

The definition includes patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects.1

Patients with severe Primary IGFD are not GH deficient, and therefore, exogenous GH treatment cannot be expected to resolve the patient's growth deficiency.1

IGF-1 and Its Role in Growth

GH and IGF-1 promote growth both in concert and independently, however IGF-1 is the principal hormonal mediator of statural growth.1

Pivotal Role of IGF-1 in Growth

Some patients previously classified incorrectly as having Idiopathic Short Stature (ISS) or as GH Insensitivity may actually have Primary IGFD.18 IGF-1 and other components of the IGF system, including IGF-binding protein 3 (IGFBP-3) are now established markers that can be measured and used in the classification of these growth disorders.11 The pivotal role of IGF-1 in postnatal growth has altered the "GH-centric" approach to the diagnosis of growth disorders.15

Indication and Important Safety Information

INCRELEX® (mecasermin [rDNA origin] injection) is indicated for the treatment of growth failure in children with severe primary IGF-1 deficiency, or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. Severe primary IGF-1 deficiency (IGFD) is defined by height standard deviation score ≤ -3.0 and basal IGF-1 standard deviation score ≤ -3.0 and normal or elevated growth hormone (GH). Severe Primary IGFD includes classical and other forms of growth hormone insensitivity. Patients with Primary IGFD may have mutations in the GH receptor (GHR), post-GHR signaling pathway including the IGF-1 gene. They are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment.

INCRELEX is not intended for use in subjects with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids. Thyroid and nutritional deficiencies should be corrected before initiating INCRELEX treatment.

Limitations of use: INCRELEX is not a substitute to GH for approved GH indications.

INCRELEX is contraindicated in the presence of active or suspected malignancy, and therapy should be discontinued if evidence of malignancy develops. INCRELEX should not be used by patients who are allergic to mecasermin (rhIGF-1) or any of the inactive ingredients in INCRELEX, or who have experienced a severe hypersensitivity to INCRELEX [see Warnings and Precautions and Adverse Reactions]. Intravenous administration of INCRELEX is contraindicated. INCRELEX should not be used for growth promotion in patients with closed epiphyses.

INCRELEX has insulin-like hypoglycemic effects and should be administered 20 minutes before or after a meal or snack. Hypersensitivity and allergic reactions have been reported, including a low number of cases indicative of anaphylaxis requiring hospitalization. Intracranial hypertension has occurred in patients treated with INCRELEX. Funduscopic examination is recommended at the initiation of and periodically during the course of therapy. Patients should have periodic examinations to rule out potential complications from tonsillar/adenoidal hypertrophy and receive appropriate treatment if necessary. Children with onset of limp or hip/knee pain should be evaluated for possible slipped capital femoral epiphysis. Monitor any child with scoliosis for progression of the spine curve.

In clinical studies of 71 pediatric subjects with severe Primary IGFD representing 274 patient-years of treatment, no subjects discontinued due to adverse events. Hypoglycemia was reported by 30 subjects (42%) at least once during their course of therapy with INCRELEX. Most cases of hypoglycemia were mild or moderate in severity. Five subjects had severe hypoglycemia (requiring assistance and treatment) on one or more occasion and four subjects experienced hypoglycemic seizures/loss of consciousness on one or more occasion. Symptomatic hypoglycemia was generally avoided when a meal or snack was consumed either shortly (i.e., 20 minutes) before or after the administration of INCRELEX. Tonsillar hypertrophy was noted in 11 (15%) subjects in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years. Intracranial hypertension occurred in three subjects. In two subjects the events resolved without interruption of INCRELEX treatment. INCRELEX treatment was discontinued in the third subject and resumed later at a lower dose without recurrence.

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