Clinical overview of chronic granulomatous disease (CGD)

NADPH oxidase: the biochemical basis of CGD

See how a mutation in any of the 5 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
component genes can lead to life-threatening bacterial and fungal infections.

What is chronic granulomatous disease?

CGD is a rare inherited primary immunodeficiency disorder where the immune system does not work properly. This primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) results in impaired killing of fungi and bacteria, which can lead to severe and recurrent infections.^1,2

CGD life expectancy

With the development of preventative therapies and early recognition of infectious complications, 90% of children with CGD now survive into adulthood. This remains, however, largely dependent on several factors, including time of diagnosis, access to care, expertise of caregiver, adherence to therapy, and lifestyle modifications.^3,4

Inheriting CGD

CGD can be inherited in 2 ways:

X-linked CGD is passed down from the carrier mother and is the most common form of CGD. It primarily affects male children, and symptoms usually appear early in childhood.^3,5
Autosomal recessive CGD presents later in life, which can delay diagnosis. Serious infections* may be less frequent.⁶ Autosomal recessive CGD is passed down by 2 carrier parents and can affect both male and female children.

X-linked CGD Carriers

X-linked carriers can experience various symptoms and may be at risk for serious infections. Carriers may experience CGD-related
lupus-like symptoms including^3,7-9

Skin rash
Sensitivity to the sun
Pain and swelling of the joints
Feeling tired all the time
Weight loss

Identifying CGD

Knowing what to look for can aid in the diagnosis of CGD. Suspect CGD in a patient with

Frequent, repeat infections
Unusually severe infections
Infections from a specific group of pathogens

CGD lifestyle modifications

Infections can be caused by bacteria and fungi from many places. They live in places like gardens (in mulch), playgrounds (in woodchips), and in lakes and ponds. People with CGD can still enjoy outdoor activities, but they should be cautioned to stay away from these places. Patients with CGD should also avoid the following

Raking leaves or being around someone raking leaves
Barns, caves, and other musty places
Hay rides
Smoking or being around someone smoking

Benefits of early diagnosis and treating CGD

Early diagnosis and prophylactic treatment benefits patients with CGD because they have a higher incidence of serious infections* relative to the normal population. Serious infections* can be life-threatening and result in long hospital stays.^1,3

To help protect patients with CGD against serious infections,* triple prophylactic therapy consisting of antibiotics, antifungals, and Interferon gamma, such as ACTIMMUNE, is recommended by the^10,11

ACTIMMUNE is the only FDA-approved therapy indicated for reducing the frequency and severity of serious infections* associated with CGD.^12,13

*Serious infection is defined as a clinical event requiring hospitalization and/or intravenous antibiotics.

Stay informed about ACTIMMUNE and CGD

References

1. Leiding JW, Holland SM. Chronic granulomatous disease. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews^® Washington, Seattle; 1993-2022. 2. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine. 2000;79(3):155-169. 3. Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010;38(1):3-10. 4. Thomsen IP, Smith MA, Holland SM, et al. A comprehensive approach to the management of children and adults with chronic granulomatous disease. J Allergy Clin Immunol Pract. 2016;4(6):1082-1088. 5. Rider NL, Jameson MB, Creech CB. Chronic granulomatous disease: epidemiology, pathophysiology, and genetic basis of disease. J Pediatric Infect Dis Soc. 2018;7(suppl 1):S2-S5. 6. Holland SM. Chronic granulomatous disease. Hematol Oncol Clin North Am. 2013;27(1):89-99. 7. Battersby AC, Bruggins H, Pearce MS, et al. Inflammatory and autoimmune manifestations in X-linked carriers of chronic granulomatous disease in the United Kingdom. J Allergy Clin Immunol. 2017;140(2):628-630.e6. 8. Marciano BE, Zerbe CS, Falcone EL, et al. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol. 2018;141(1):365-371. 9. Song E, Jaishankar GB, Saleh H, Jithpratuck W, Sahni R, Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011;9(1):10-24. 10. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeﬁciency. J Allergy Clin Immunol. 2015;136(5):1186-1205.e1-e78. 11. Leiding JW, Malech HL, Holland SM. Chronic granulomatous disease. Clinical Focus on Primary Immunodeﬁciencies. 2013;15:1-9. 12. ACTIMMUNE (Interferon gamma-1b) [prescribing information] Amgen. 13. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991;324(8):509-516.

Approved Uses and Important Safety Information

INDICATIONS AND USAGE

ACTIMMUNE^® (Interferon gamma-1b) is indicated:

For reducing the frequency and severity of serious infections associated with chronic granulomatous disease
For delaying time to disease progression in patients with severe, malignant osteopetrosis

Important Safety Information

CONTRAINDICATIONS

In patients who develop or have known hypersensitivity to interferon gamma-1b, E. coli -derived products, or any component of the product

WARNINGS AND PRECAUTIONS

ACTIMMUNE should be used with caution in patients with:
- Pre-existing cardiac conditions, including ischemia, congestive heart failure, or arrhythmia
- Seizure disorders or compromised central nervous system function
- Myelosuppression or receiving other potentially myelosuppressive agents
- Severe renal insufficiency
- Age <1 year
Monitoring:
- Before starting ACTIMMUNE and every 3 months during treatment, hematologic tests, blood chemistries, and urinalysis are recommended for all patients
- Patients begun on ACTIMMUNE before the age of 1 year should receive monthly assessments of liver function. If severe hepatic enzyme elevations develop, ACTIMMUNE dosage should be modified
- Monitor renal function regularly when administering ACTIMMUNE in patients with severe renal insufficiency; accumulation of interferon gamma-1b may occur with repeated administration. Renal toxicity has been reported in patients receiving ACTIMMUNE

USE IN SPECIFIC POPULATIONS

ACTIMMUNE should be used during pregnancy only if the potential benefit to the patient outweighs the potential risk to the fetus
It is not known if ACTIMMUNE is excreted in human milk, so either ACTIMMUNE or nursing should be discontinued dependent on the importance of the drug to the patient
In younger patients, long-term effects of ACTIMMUNE on fertility are not known
In animal studies, both male and female fertility was negatively impacted by doses significantly higher than the maximum clinical dose

DRUG INTERACTIONS

Concomitant use of drugs with neurotoxic, hematotoxic, or cardiotoxic effects may increase the toxicity of interferons
Avoid simultaneous administration of ACTIMMUNE with other heterologous serum protein or immunological preparations (eg, vaccines)

ADVERSE REACTIONS

The most common adverse experiences occurring with ACTIMMUNE therapy are “flu-like” symptoms such as fever, headache, chills, myalgia, or fatigue, which may decrease in severity as treatment continues, and may be minimized by bedtime administration of ACTIMMUNE. Acetaminophen may be used to prevent or partially alleviate the fever and headache
Isolated cases of acute serious hypersensitivity reactions have been observed in patients receiving ACTIMMUNE
Reversible neutropenia, thrombocytopenia, and elevations of AST and/or ALT have been observed during ACTIMMUNE therapy
At doses 10 times greater than the weekly recommended dose, ACTIMMUNE may exacerbate pre-existing cardiac conditions, or may cause reversible neurological effects such as decreased mental status, gait disturbance, and dizziness

Please see Full Prescribing Information for additional safety information.

Approved Uses and Important Safety Information

INDICATIONS AND USAGE

ACTIMMUNE^® (Interferon gamma-1b) is indicated:

For reducing the frequency and severity of serious infections associated with chronic granulomatous disease
For delaying time to disease progression in patients with severe, malignant osteopetrosis

Important Safety Information

CONTRAINDICATIONS

In patients who develop or have known hypersensitivity to interferon gamma-1b, E. coli -derived products, or any component of the product

WARNINGS AND PRECAUTIONS

ACTIMMUNE should be used with caution in patients with:
- Pre-existing cardiac conditions, including ischemia, congestive heart failure, or arrhythmia
- Seizure disorders or compromised central nervous system function
- Myelosuppression or receiving other potentially myelosuppressive agents
- Severe renal insufficiency
- Age 1 year
Monitoring:
- Before starting ACTIMMUNE and every 3 months during treatment, hematologic tests, blood chemistries, and urinalysis are recommended for all patients
- Patients begun on ACTIMMUNE before the age of 1 year should receive monthly assessments of liver function. If severe hepatic enzyme elevations develop, ACTIMMUNE dosage should be modified
- Monitor renal function regularly when administering ACTIMMUNE in patients with severe renal insufficiency; accumulation of interferon gamma-1b may occur with repeated administration. Renal toxicity has been reported in patients receiving ACTIMMUNE

USE IN SPECIFIC POPULATIONS

ACTIMMUNE should be used during pregnancy only if the potential benefit to the patient outweighs the potential risk to the fetus
It is not known if ACTIMMUNE is excreted in human milk, so either ACTIMMUNE or nursing should be discontinued dependent on the importance of the drug to the patient
In younger patients, long-term effects of ACTIMMUNE on fertility are not known
In animal studies, both male and female fertility was negatively impacted by doses significantly higher than the maximum clinical dose

DRUG INTERACTIONS

Concomitant use of drugs with neurotoxic, hematotoxic, or cardiotoxic effects may increase the toxicity of interferons
Avoid simultaneous administration of ACTIMMUNE with other heterologous serum protein or immunological preparations (eg, vaccines)

ADVERSE REACTIONS

The most common adverse experiences occurring with ACTIMMUNE therapy are “flu-like” symptoms such as fever, headache, chills, myalgia, or fatigue, which may decrease in severity as treatment continues, and may be minimized by bedtime administration of ACTIMMUNE. Acetaminophen may be used to prevent or partially alleviate the fever and headache
Isolated cases of acute serious hypersensitivity reactions have been observed in patients receiving ACTIMMUNE
Reversible neutropenia, thrombocytopenia, and elevations of AST and/or ALT have been observed during ACTIMMUNE therapy
At doses 10 times greater than the weekly recommended dose, ACTIMMUNE may exacerbate pre-existing cardiac conditions, or may cause reversible neurological effects such as decreased mental status, gait disturbance, and dizziness

Please see Full Prescribing Information for additional safety information.

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Clinical overview of chronic granulomatous disease (CGD)

Stay informed about ACTIMMUNE and CGD

Approved Uses and Important Safety Information

Approved Uses and Important Safety Information