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.

ABSTRACT: PURPOSE:To investigate immune tolerance induction with transient low-dose methotrexate (TLD-MTX) initiated with recombinant human acid ?-glucosidase (rhGAA), in treatment-naïve 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.

SUBMITTER: Kazi ZB 

PROVIDER: S-EPMC6417984 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature