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Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease.
Genet Med 2012; 14(1):135-42GM

Abstract

PURPOSE

Infantile Pompe disease resulting from a deficiency of lysosomal acid α-glucosidase (GAA) requires enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA). Cross-reactive immunologic material negative (CRIM-negative) Pompe patients develop high-titer antibody to the rhGAA and do poorly. We describe successful tolerance induction in CRIM-negative patients.

METHODS

Two CRIM-negative patients with preexisting anti-GAA antibodies were treated therapeutically with rituximab, methotrexate, and gammaglobulins. Two additional CRIM-negative patients were treated prophylactically with a short course of rituximab and methotrexate, in parallel with initiating rhGAA.

RESULTS

In both patients treated therapeutically, anti-rhGAA was eliminated after 3 and 19 months. All four patients are immune tolerant to rhGAA, off immune therapy, showing B-cell recovery while continuing to receive ERT at ages 36 and 56 months (therapeutic) and 18 and 35 months (prophylactic). All patients show clinical response to ERT, in stark contrast to the rapid deterioration of their nontolerized CRIM-negative counterparts.

CONCLUSION

The combination of rituximab with methotrexate ± intravenous gammaglobulins (IVIG) is an option for tolerance induction of CRIM-negative Pompe to ERT when instituted in the naïve setting or following antibody development. It should be considered in other conditions in which antibody response to the therapeutic protein elicits robust antibody response that interferes with product efficacy.

Authors+Show Affiliations

Pediatric Hematology/Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA. yoav.messinger@childrensmn.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22237443

Citation

Messinger, Yoav H., et al. "Successful Immune Tolerance Induction to Enzyme Replacement Therapy in CRIM-negative Infantile Pompe Disease." Genetics in Medicine : Official Journal of the American College of Medical Genetics, vol. 14, no. 1, 2012, pp. 135-42.
Messinger YH, Mendelsohn NJ, Rhead W, et al. Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Genet Med. 2012;14(1):135-42.
Messinger, Y. H., Mendelsohn, N. J., Rhead, W., Dimmock, D., Hershkovitz, E., Champion, M., ... Kishnani, P. S. (2012). Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 14(1), pp. 135-42. doi:10.1038/gim.2011.4.
Messinger YH, et al. Successful Immune Tolerance Induction to Enzyme Replacement Therapy in CRIM-negative Infantile Pompe Disease. Genet Med. 2012;14(1):135-42. PubMed PMID: 22237443.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. AU - Messinger,Yoav H, AU - Mendelsohn,Nancy J, AU - Rhead,William, AU - Dimmock,David, AU - Hershkovitz,Eli, AU - Champion,Michael, AU - Jones,Simon A, AU - Olson,Rebecca, AU - White,Amy, AU - Wells,Cara, AU - Bali,Deeksha, AU - Case,Laura E, AU - Young,Sarah P, AU - Rosenberg,Amy S, AU - Kishnani,Priya S, PY - 2012/1/13/entrez PY - 2012/1/13/pubmed PY - 2012/5/16/medline SP - 135 EP - 42 JF - Genetics in medicine : official journal of the American College of Medical Genetics JO - Genet. Med. VL - 14 IS - 1 N2 - PURPOSE: Infantile Pompe disease resulting from a deficiency of lysosomal acid α-glucosidase (GAA) requires enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA). Cross-reactive immunologic material negative (CRIM-negative) Pompe patients develop high-titer antibody to the rhGAA and do poorly. We describe successful tolerance induction in CRIM-negative patients. METHODS: Two CRIM-negative patients with preexisting anti-GAA antibodies were treated therapeutically with rituximab, methotrexate, and gammaglobulins. Two additional CRIM-negative patients were treated prophylactically with a short course of rituximab and methotrexate, in parallel with initiating rhGAA. RESULTS: In both patients treated therapeutically, anti-rhGAA was eliminated after 3 and 19 months. All four patients are immune tolerant to rhGAA, off immune therapy, showing B-cell recovery while continuing to receive ERT at ages 36 and 56 months (therapeutic) and 18 and 35 months (prophylactic). All patients show clinical response to ERT, in stark contrast to the rapid deterioration of their nontolerized CRIM-negative counterparts. CONCLUSION: The combination of rituximab with methotrexate ± intravenous gammaglobulins (IVIG) is an option for tolerance induction of CRIM-negative Pompe to ERT when instituted in the naïve setting or following antibody development. It should be considered in other conditions in which antibody response to the therapeutic protein elicits robust antibody response that interferes with product efficacy. SN - 1530-0366 UR - https://www.unboundmedicine.com/medline/citation/22237443/Successful_immune_tolerance_induction_to_enzyme_replacement_therapy_in_CRIM_negative_infantile_Pompe_disease_ L2 - http://dx.doi.org/10.1038/gim.2011.4 DB - PRIME DP - Unbound Medicine ER -