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
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.
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