Pompe disease in adulthood: effects of antibody formation on enzyme replacement therapy

To determine the effect of antibodies against recombinant human acid α-glucosidase (rhGAA) on treatment efficacy and safety, and to test whether the GAA genotype is involved in antibody formation. We used enzyme-linked immunosorbent assay (ELISA) to determine anti-rhGAA antibody titers at baseline and at 6, 12, and 36 months of rhGAA treatment. We measured the capacity of antibodies to neutralize rhGAA enzymatic activity or cellular uptake and the effects on infusion-associated reactions (IARs), muscle strength, and pulmonary function. Of 73 patients, 45 developed antibodies. Maximal titers were high (≥1:31,250) in 22% of patients, intermediate (1:1,250–1:31,250) in 40%, and none or low (0–1:1,250) in 38%. The common IVS1/delex18 GAA genotype was absent only in the high-titer group. The height of the titer positively correlated with the occurrence and number of IARs (P ≤ 0.001). On the group level, antibody titers did not correlate with treatment efficacy. Eight patients (11%) developed very high maximal titers (≥156,250), but only one patient showed high sustained neutralizing antibodies that probably interfered with treatment efficacy. In adults with Pompe disease, antibody formation does not interfere with rhGAA efficacy in the majority of patients, is associated with IARs, and may be attenuated by the IVS1/delex18 GAA genotype. Genet Med 19 1, 90–97.