Antibody formation and efficacy of enzyme replacement therapy in adults with Pompe disease: Unlocking long-term insights

PURPOSE: Anti-recombinant human acid α-glucosidase (rhGAA) antibodies can develop in adult Pompe patients receiving enzyme replacement therapy (ERT), but their long-term impact on clinical treatment outcomes is currently unclear. METHODS: Pompe patients starting ERT ≥18 years of age were monitored for anti-rhGAA antibody titers (at start of ERT and designated time points thereafter) and its neutralizing activity. Six-minute walk test and forced vital capacity were assessed to evaluate clinical outcomes. RESULTS: We studied the antibody titer course (n = 930) of 111 patients. High peak titers (≥31,250) were found in 34/111 patients, with high sustained antibody titers in 21/34. High titers were linked to more infusion associated reactions (IARs; P = .008). Patients with high peak antibody titers had more stable supine lung function and 6-minute walk test distance compared with those with high sustained antibody titers (P =.02) or low/intermediate titers (P =.03). No other group-level differences in outcomes were found. Neutralizing activity was detected in 9 patients without group-level impact; however, this activity or high antibody levels negatively affected disease course in some. CONCLUSION: High (sustained) antidrug antibody titers are associated with an increased risk of IARs. Although they do not appear to significantly impact clinical outcomes at the group level, their (neutralizing) effect can negatively affect disease course in individual patients.