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Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT.
PLoS One 2013; 8(6):e67052Plos

Abstract

OBJECTIVE

Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount a strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that immune tolerance induction (ITI) prevents or diminishes the development of antibody titers, resulting in a better clinical outcome compared to CN IPD patients treated with ERT monotherapy.

METHODS

We evaluated the safety, efficacy and feasibility of a clinical algorithm designed to accurately identify CN IPD patients and minimize delays between CRIM status determination and initiation of an ITI regimen (combination of rituximab, methotrexate and IVIG) concurrent with ERT. Clinical and laboratory data including measures of efficacy analysis for response to ERT were analyzed and compared to CN IPD patients treated with ERT monotherapy.

RESULTS

Seven CN IPD patients were identified and started on the ITI regimen concurrent with ERT. Median time from diagnosis of CN status to commencement of ERT and ITI was 0.5 months (range: 0.1-1.6 months). At baseline, all patients had significant cardiomyopathy and all but one required respiratory support. The ITI regimen was safely tolerated in all seven cases. Four patients never seroconverted and remained antibody-free. One patient died from respiratory failure. Two patients required another course of the ITI regimen. In addition to their clinical improvement, the antibody titers observed in these patients were much lower than those seen in ERT monotherapy treated CN patients.

CONCLUSIONS

The ITI regimen appears safe and efficacious and holds promise in altering the natural history of CN IPD by increasing ERT efficacy. An algorithm such as this substantiates the benefits of accelerated diagnosis and management of CN IPD patients, thus, further supporting the importance of early identification and treatment initiation with newborn screening for IPD.

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States of America.No 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 availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23825616

Citation

Banugaria, Suhrad G., et al. "Algorithm for the Early Diagnosis and Treatment of Patients With Cross Reactive Immunologic Material-negative Classic Infantile Pompe Disease: a Step Towards Improving the Efficacy of ERT." PloS One, vol. 8, no. 6, 2013, pp. e67052.
Banugaria SG, Prater SN, Patel TT, et al. Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT. PLoS ONE. 2013;8(6):e67052.
Banugaria, S. G., Prater, S. N., Patel, T. T., Dearmey, S. M., Milleson, C., Sheets, K. B., ... Kishnani, P. S. (2013). Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT. PloS One, 8(6), pp. e67052. doi:10.1371/journal.pone.0067052.
Banugaria SG, et al. Algorithm for the Early Diagnosis and Treatment of Patients With Cross Reactive Immunologic Material-negative Classic Infantile Pompe Disease: a Step Towards Improving the Efficacy of ERT. PLoS ONE. 2013;8(6):e67052. PubMed PMID: 23825616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT. AU - Banugaria,Suhrad G, AU - Prater,Sean N, AU - Patel,Trusha T, AU - Dearmey,Stephanie M, AU - Milleson,Christie, AU - Sheets,Kathryn B, AU - Bali,Deeksha S, AU - Rehder,Catherine W, AU - Raiman,Julian A J, AU - Wang,Raymond A, AU - Labarthe,Francois, AU - Charrow,Joel, AU - Harmatz,Paul, AU - Chakraborty,Pranesh, AU - Rosenberg,Amy S, AU - Kishnani,Priya S, Y1 - 2013/06/25/ PY - 2013/02/10/received PY - 2013/05/13/accepted PY - 2013/7/5/entrez PY - 2013/7/5/pubmed PY - 2014/2/8/medline SP - e67052 EP - e67052 JF - PloS one JO - PLoS ONE VL - 8 IS - 6 N2 - OBJECTIVE: Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount a strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that immune tolerance induction (ITI) prevents or diminishes the development of antibody titers, resulting in a better clinical outcome compared to CN IPD patients treated with ERT monotherapy. METHODS: We evaluated the safety, efficacy and feasibility of a clinical algorithm designed to accurately identify CN IPD patients and minimize delays between CRIM status determination and initiation of an ITI regimen (combination of rituximab, methotrexate and IVIG) concurrent with ERT. Clinical and laboratory data including measures of efficacy analysis for response to ERT were analyzed and compared to CN IPD patients treated with ERT monotherapy. RESULTS: Seven CN IPD patients were identified and started on the ITI regimen concurrent with ERT. Median time from diagnosis of CN status to commencement of ERT and ITI was 0.5 months (range: 0.1-1.6 months). At baseline, all patients had significant cardiomyopathy and all but one required respiratory support. The ITI regimen was safely tolerated in all seven cases. Four patients never seroconverted and remained antibody-free. One patient died from respiratory failure. Two patients required another course of the ITI regimen. In addition to their clinical improvement, the antibody titers observed in these patients were much lower than those seen in ERT monotherapy treated CN patients. CONCLUSIONS: The ITI regimen appears safe and efficacious and holds promise in altering the natural history of CN IPD by increasing ERT efficacy. An algorithm such as this substantiates the benefits of accelerated diagnosis and management of CN IPD patients, thus, further supporting the importance of early identification and treatment initiation with newborn screening for IPD. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23825616/Algorithm_for_the_early_diagnosis_and_treatment_of_patients_with_cross_reactive_immunologic_material_negative_classic_infantile_pompe_disease:_a_step_towards_improving_the_efficacy_of_ERT_ L2 - http://dx.plos.org/10.1371/journal.pone.0067052 DB - PRIME DP - Unbound Medicine ER -