NYMC Faculty Publications
An Immune Tolerance Approach Using Transient Low-Dose Methotrexate in the ERT-Naive Setting of Patients Treated with a Therapeutic Protein: Experience in Infantile-Onset Pompe Disease
DOI
10.1038/s41436-018-0270-7
Journal Title
Genetics in Medicine
First Page
887
Last Page
895
Document Type
Article
Publication Date
April 2019
Department
Pediatrics
Keywords
Pompe disease, alglucosidase alfa, antidrug antibodies, methotrexate, prophylactic immune tolerance induction
Disciplines
Medicine and Health Sciences
Abstract
PURPOSE: To investigate immune tolerance induction with transient low-dose methotrexate (TLD-MTX) initiated with recombinant human acid alpha-glucosidase (rhGAA), in treatment-naive cross-reactive immunologic material (CRIM)-positive infantile-onset Pompe disease (IOPD) patients. METHODS: Newly diagnosed IOPD patients received subcutaneous or oral 0.4 mg/kg TLD-MTX for 3 cycles (3 doses/cycle) with the first 3 rhGAA infusions. Anti-rhGAA IgG titers, classified as high-sustained (HSAT; >/=51,200, >/=2 times after 6 months), sustained intermediate (SIT; >/=12,800 and <51,200 within 12 months), or low (LT; =6400 within 12 months), were compared with those of 37 CRIM-positive IOPD historic comparators receiving rhGAA alone. RESULTS: Fourteen IOPD TLD-MTX recipients at the median age of 3.8 months (range, 0.7-13.5 months) had a median last titer of 150 (range, 0-51,200) at median rhGAA duration ~83 weeks (range, 36-122 weeks). One IOPD patient (7.1%) developed titers in the SIT range and one patient (7.1%) developed titers in the HSAT range. Twelve of the 14 patients (85.7%) that received TLD-MTX remained LT, versus 5/37 HSAT (peak 51,200-409,600), 7/37 SIT (12,800-51,000), and 23/37 LT (200-12,800) among comparators. CONCLUSION: Results of TLD-MTX coinitiated with rhGAA are encouraging and merit a larger longitudinal study.
Recommended Citation
Kazi, Z., Desai, A., Troxler, R., Kronn, D., Packman, S., Sabbadini, M., Rizzo, W., & Kishnani, P. (2019). An Immune Tolerance Approach Using Transient Low-Dose Methotrexate in the ERT-Naive Setting of Patients Treated with a Therapeutic Protein: Experience in Infantile-Onset Pompe Disease. Genetics in Medicine, 21 (4), 887-895. https://doi.org/10.1038/s41436-018-0270-7