BACKGROUND: Cross-reactive immunological material-negative (CRIM-negative) infantile Pompe disease (IPD) patients develop an immune response against enzyme replacement therapy (ERT) with alglucosidase alfa that nullifies ERT efficacy. Prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG successfully prevents development of deleterious rhGAA IgG antibodies; however, safety, likelihood of success, and long-term efficacy of ITI in a larger cohort remain unknown. METHODS: Clinical data were analyzed for 19 CRIM-negative IPD patients who received ITI with rituximab, methotrexate, and IVIG in the ERT-naive setting (ERT+ITI) and compared to a historical cohort of 10 CRIM-negative IPD patients on ERT monotherapy. RESULTS: ITI was safely tolerated, although infections were reported in 4 patients. Fourteen (74%) ERT+ITI patients were alive, with a median age of 44.2 months at their final assessment. The eldest survivor was 103.9 months old, with 100.2 months of follow-up after initiation of ERT+ITI. Death (n = 5) occurred at a median age of 29.2 months and was unrelated to the administration of ITI. Fifteen patients either did not seroconvert (n = 8) or maintained low titers (n = 7; defined as titers of /=51,200 at or beyond 6 months on ERT). Left ventricular mass index (LVMI) decreased from a median of 248.5 g/m2 at baseline to 76.8 g/m2 at a median time from ERT+ITI initiation to 59 weeks. ERT+ITI significantly improved overall survival (P = 0.001), eliminated/reduced antibodies at values of
Kazi, Z., Desai, A., Berrier, K., Troxler, R., Wang, R., Abdul-Rahman, O., Tanpaiboon, P., Mendelsohn, N., Herskovitz, E., Kronn, D., Inbar-Feigenberg, M., Ward-Melver, C., Polan, M., Gupta, P., Rosenberg, A., & Kishnani, P. (2017). Sustained Immune Tolerance Induction in Enzyme Replacement Therapy-Treated CRIM-Negative Patients with Infantile Pompe Disease. JCI Insight, 2 (16), e94328. https://doi.org/10.1172/jci.insight.94328
Originally published in JCI Insight, 2(14):e94328. The original material can be found here.