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; \u3e/=51,200, \u3e/=2 times after 6 months), sustained intermediate (SIT; \u3e/=12,800 and \u3c51,200 within 12 months), or low (LT