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.
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.
Type
Journal articleSubject
AlgorithmsAntibodies, Monoclonal, Murine-Derived
Clinical Laboratory Techniques
Cross Reactions
Early Diagnosis
Enzyme Replacement Therapy
Female
Glycogen Storage Disease Type II
Humans
Immunoglobulins
Immunosuppression
Infant
Infant, Newborn
Male
Methotrexate
Rituximab
Safety
Time Factors
Treatment Outcome
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https://hdl.handle.net/10161/15373Published Version (Please cite this version)
10.1371/journal.pone.0067052Publication Info
Banugaria, SG; Prater, SN; Patel, TT; Dearmey, Stephanie; Milleson, Christie; Sheets,
KB; ... Kishnani, Priya Sunil (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. 10.1371/journal.pone.0067052. Retrieved from https://hdl.handle.net/10161/15373.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Deeksha Sarihyan Bali
Professor of Pediatrics
1)Development of new non-invasive laboratory diagnostic methods using enzymology and
molecular diagnostic techniques for Glycogen Storage Diseases (GSDs) and Lysoosmal
Storage Diseases (LSDs) like Pompe, Fabry, Gaucher, MPS - for early diagnosis and
treatment modalities. Exploration of new high throughput diagnostic platforms with
an idea of implementation into New born screening (NBS)of these diseases. 2)Clinical
research studies associated with Pompe disease with a goal to imp
Priya Sunil Kishnani
Chen Family Professor of Pediatrics
RESEARCH INTERESTS A multidisciplinary approach to care of individuals with genetic
disorders in conjunction with clinical and bench research that contributes to: 1)
An understanding of the natural history and delineation of long term complications
of genetic disorders 2) The development of new therapies for genetic disorders through
translational research 3) The development and execution of large multicenter trials
to confirm safety and efficacy of potential th
Rebeccah Catherine Rehder
Associate Professor of Pathology
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