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Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease.

Publication ,  Journal Article
Banugaria, SG; Prater, SN; McGann, JK; Feldman, JD; Tannenbaum, JA; Bailey, C; Gera, R; Conway, RL; Viskochil, D; Kobori, JA; Rosenberg, AS ...
Published in: Genet Med
February 2013

PURPOSE: High sustained antibody titers complicate many disorders treated with a therapeutic protein, including those treated with enzyme replacement therapy, such as Pompe disease. Although enzyme replacement therapy with alglucosidase alfa (Myozyme) in Pompe disease has improved the prognosis of this otherwise lethal disorder, patients who develop high sustained antibody titers to alglucosidase alfa enter a prolonged phase of clinical decline resulting in death despite continued enzyme replacement therapy. Clinically effective immune-tolerance induction strategies have yet to be described in the setting of an entrenched immune response characterized by high sustained antibody titers, wherein antibody-producing plasma cells play an especially prominent role. METHODS: We treated three patients with infantile Pompe disease experiencing marked clinical decline due to high sustained antibody titers. To target the plasma cell source of high sustained antibody titers, a regimen based on bortezomib (Velcade) was used in combination with rituximab, methotrexate, and intravenous immunoglobulin. RESULTS: The treatment regimen was well tolerated, with no obvious side effects. Patient 1 had a 2,048-fold, and patients 2 and 3 each had a 64-fold, reduction in anti-alglucosidase alfa antibody titer, with concomitant sustained clinical improvement. CONCLUSION: The addition of bortezomib to immunomodulatory regimens is an effective and safe treatment strategy in infantile Pompe disease, with potentially broader clinical implications.

Duke Scholars

Published In

Genet Med

DOI

EISSN

1530-0366

Publication Date

February 2013

Volume

15

Issue

2

Start / End Page

123 / 131

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyrazines
  • Plasma Cells
  • Methotrexate
  • Male
  • Immunoglobulins, Intravenous
  • Humans
  • Glycogen Storage Disease Type II
  • Genetics & Heredity
  • Drug Therapy, Combination
 

Citation

APA
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MLA
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Banugaria, S. G., Prater, S. N., McGann, J. K., Feldman, J. D., Tannenbaum, J. A., Bailey, C., … Kishnani, P. S. (2013). Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease. Genet Med, 15(2), 123–131. https://doi.org/10.1038/gim.2012.110
Banugaria, Suhrad G., Sean N. Prater, Judeth K. McGann, Jonathan D. Feldman, Jesse A. Tannenbaum, Carrie Bailey, Renuka Gera, et al. “Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease.Genet Med 15, no. 2 (February 2013): 123–31. https://doi.org/10.1038/gim.2012.110.
Banugaria SG, Prater SN, McGann JK, Feldman JD, Tannenbaum JA, Bailey C, et al. Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease. Genet Med. 2013 Feb;15(2):123–31.
Banugaria, Suhrad G., et al. “Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease.Genet Med, vol. 15, no. 2, Feb. 2013, pp. 123–31. Pubmed, doi:10.1038/gim.2012.110.
Banugaria SG, Prater SN, McGann JK, Feldman JD, Tannenbaum JA, Bailey C, Gera R, Conway RL, Viskochil D, Kobori JA, Rosenberg AS, Kishnani PS. Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease. Genet Med. 2013 Feb;15(2):123–131.

Published In

Genet Med

DOI

EISSN

1530-0366

Publication Date

February 2013

Volume

15

Issue

2

Start / End Page

123 / 131

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Pyrazines
  • Plasma Cells
  • Methotrexate
  • Male
  • Immunoglobulins, Intravenous
  • Humans
  • Glycogen Storage Disease Type II
  • Genetics & Heredity
  • Drug Therapy, Combination