Skip to main content
SpringerLink
Log in

Interferon γ-1b in chronic granulomatous disease and severe malignant osteopetrosis: a guide to its use in the USA

  • Adis Drug Clinical Q&A
  • Published:
Drugs & Therapy Perspectives Aims and scope Submit manuscript

Abstract

In the USA, subcutaneous interferon γ-1b (Actimmune®) is indicated to reduce the frequency and severity of serious infections associated with chronic granulomatous disease and delay the time to disease progression in patients with severe malignant (autosomal recessive) osteopetrosis. The mechanism of action of interferon γ-1b in these conditions is complex and involves factors that are additional to the stimulation of superoxide production by phagocytes. The primary tolerability issues associated with interferon γ-1b are mild to moderate fever and other flu-like symptoms, which are generally manageable with symptomatic treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Holland SM. Chronic granulomatous disease: from a fatal disease to a curable one. In: Etzioni A, Ochs HD, editors. Primary immunodeficiency disorders: a historic and scientific perspective. Oxford: Elsevier Inc.; 2014. p. 151–70.

    Google Scholar 

  2. Song E, Jaishankar GB, Saleh H, et al. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011;9(1):10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Meischl C, Roos D. The molecular basis of chronic granulomatous disease. Springer Semin Immunopathol. 1998;19(4):417–34.

    Article  CAS  PubMed  Google Scholar 

  4. Roos K, Kuhns DB, Maddalena A, et al. Hematologically important mutations: X-linked chronic granulomatous disease (third update). Blood Cells Mol Dis. 2010;45(3):246–65.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Kuhns DB, Alvord WG, Heller T, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Kang EM, Marciano BE, DeRavin S, et al. Chronic granulomatous disease: overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2011;127(6):1319–26.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Stark Z, Savarirayan R. Osteopetrosis. Orphanet J Rare Dis. 2009;4:5.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Shankar L, Gerritsen EJ, Kelly LL Jr. Osteopetrosis: pathogenesis and rationale for the use of interferon-γ-1b. BioDrugs. 1997;7(1):23–9.

    Article  CAS  PubMed  Google Scholar 

  9. Sobacchi C, Schulz A, Coxon FP, et al. Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nat Rev Endocrinol. 2013;9(9):522–36.

    Article  CAS  PubMed  Google Scholar 

  10. Weber DR, Econs MJ, Levine MA. Osteopetrosis: pathogenesis, management and future directions for research. IBMS BoneKEy. 2014;11:520.

    Article  Google Scholar 

  11. Actimmune® (interferon gamma-1b): US prescribing information. Roswell (GA): Vidara Therapeutics Inc., 2013.

  12. Immukin (interferon gamma-1b) solution for injection: UK summary of product characteristics. Bracknell: Boehringer Ingelheim, 2013.

  13. Todd PA, Goa KL. Interferon gamma-1b: a review of its pharmacology and therapeutic potential in chronic granulomatous disease. Drugs. 1992;43(1):111–22.

    Article  CAS  PubMed  Google Scholar 

  14. Nathan CF, Murray HW, Wiebe ME, et al. Identification of interferon-γ as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983;158(3):670–89.

    Article  CAS  PubMed  Google Scholar 

  15. Berton G, Zeni L, Cassatella MA, et al. Gamma interferon is able to enhance the oxidative metabolism of human neutrophils. Biochem Biophys Res Commun. 1986;138(3):1276–82.

    Article  CAS  PubMed  Google Scholar 

  16. Casbon AJ, Long ME, Dunn KW, et al. Effects of IFN-γ on intracellular trafficking and activity of macrophage NADPH oxidase flavocytochrome b558. J Leukoc Biol. 2012;92(4):869–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Sechler JM, Malech HL, White CJ, et al. Recombinant human interferon-γ reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci USA. 1988;85(13):4874–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Ezekowitz RA, Orkin SH, Newburger PE. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease. J Clin Invest. 1987;80(4):1009–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Ezekowitz RA, Dinauer MC, Jaffe HS, et al. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med. 1988;319(3):146–51.

    Article  CAS  PubMed  Google Scholar 

  20. Ezekowitz RA, Sieff CA, Dinauer MC, et al. Restoration of phagocyte function by interferon-γ in X-linked chronic granulomatous disease occurs at the level of a progenitor cell. Blood. 1990;76(12):2443–8.

    CAS  PubMed  Google Scholar 

  21. Newburger PE, Ezekowitz RA, Whitney C, et al. Induction of phagocyte cytochrome b heavy chain gene expression by interferon γ. Proc Natl Acad Sci USA. 1988;85(14):5215–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Rex JH, Bennett JE, Gallin JI, et al. In vivo interferon-γ therapy augments the in vitro ability of chronic granulomatous disease neutrophils to damage Aspergillus hyphae. J Infect Dis. 1991;163(4):849–52.

    Article  CAS  PubMed  Google Scholar 

  23. Åhlin A, Lärfars G, Elinder G, et al. Gamma interferon treatment of patients with chronic granulomatous disease is associated with augmented production of nitric oxide by polymorphonuclear neutrophils. Clin Diagn Lab Immunol. 1999;6(3):420–4.

    PubMed Central  PubMed  Google Scholar 

  24. 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):509–16.

    Article  Google Scholar 

  25. Key LL Jr, Ries WL, Glasscock H, et al. Osteoclastic superoxide generation: taking control of bone resorption using modulators of superoxide concentrations. Int J Tissue React. 1992;14(6):295–8.

    CAS  PubMed  Google Scholar 

  26. Madyastha PR, Yang S, Ries WL, et al. IFN-γ enhances osteoclast generation in cultures of peripheral blood from osteopetrotic patients and normalizes superoxide production. J Interferon Cytokine Res. 2000;20(7):645–52.

    Article  CAS  PubMed  Google Scholar 

  27. Hochman N, Hojo H, Hojo S, et al. Reversal of immune dysfunction in osteopetrotic rats by interferon-gamma: augmentation of macrophage Ia expression and lymphocyte interleukin-2 production and proliferation. Cell Immunol. 1991;137(1):14–23.

    Article  CAS  PubMed  Google Scholar 

  28. Duque G, Huang DC, Dion N, et al. Interferon-γ plays a role in bone formation in vivo and rescues osteoporosis in ovariectomized mice. J Bone Miner Res. 2011;26(7):1472–83.

    Article  CAS  PubMed  Google Scholar 

  29. Key LL Jr, Ries WL, Rodriquiz RM, et al. Recombinant human interferon gamma therapy for osteopetrosis. J Pediatr. 1992;121(1):119–24.

    Article  PubMed  Google Scholar 

  30. Key LL Jr, Rodriquiz RM, Willi SM, et al. Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med. 1995;332(24):1594–9.

    Article  PubMed  Google Scholar 

  31. Alam I, Gray AK, Acton D, et al. Interferon gamma, but not calcitriol improves the osteopetrotic phenotypes in ADO2 mice. J Bone Miner Res. 2015. doi:10.1002/jbmr.2545.

    Google Scholar 

  32. Marciano BE, Wesley R, De Carlo ES, et al. Long-term interferon-γ therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004;39(5):692–9.

    Article  CAS  PubMed  Google Scholar 

  33. Soler-Palacín P, Margareto C, Llobet P, et al. Chronic granulomatous disease in pediatric patients: 25 years of experience. Allergol Immunopathol (Madr). 2007;35(3):83–9.

    Article  Google Scholar 

  34. Jones LB, McGrogan P, Flood TJ, et al. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008;152(2):211–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Kobayashi S, Murayama S, Takanashi S, et al. Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan. Eur J Pediatr. 2008;167(12):1389–94.

    Article  PubMed  Google Scholar 

  36. van den Berg JM, van Koppen E, Åhlin A, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Bortoletto P, Lyman K, Camacho A, et al. Chronic granulomatous disease (CGD): a large, single-centre U.S. experience [abstract no. 3814.261 plus poster]. In: Pediatric Academic Society Annual Meeting. 2014.

  38. Devane JG, Martin ML, Matson MA. A short 2 week dose titration regimen reduces the severity of flu-like symptoms with initial interferon gamma-1b treatment. Curr Med Res Opin. 2014;30(6):1179–87.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The manuscript was reviewed by: B.S. Katz, Northwestern University Feinberg School of Medicine, Chicago, USA; S. Saluja, Saran Ashram Hospital, Dayalbagh, Agra, India

Disclosure

This article was written by a salaried employee of Adis/Springer and was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from comments received were made by the author on the basis of scientific merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Katherine A. Lyseng-Williamson

Authors
  1. Katherine A. Lyseng-Williamson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katherine A. Lyseng-Williamson.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lyseng-Williamson, K.A. Interferon γ-1b in chronic granulomatous disease and severe malignant osteopetrosis: a guide to its use in the USA. Drugs Ther Perspect 31, 213–220 (2015). https://doi.org/10.1007/s40267-015-0222-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40267-015-0222-0

Keywords

Search

Navigation