Transforming the clinical outcome in CRIM-negative infantile Pompe disease identified via newborn screening: the benefits of early treatment with enzyme replacement therapy and immune tolerance induction.
Transforming the clinical outcome in CRIM-negative infantile Pompe disease identified via newborn screening: the benefits of early treatment with enzyme replacement therapy and immune tolerance induction.
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DOI：
10.1038/s41436-020-01080-y
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发表时间：
2021-05
期刊：
影响因子：
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通讯作者：
Kishnani PS
中科院分区：
文献类型：
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作者：
Li C;Desai AK;Gupta P;Dempsey K;Bhambhani V;Hopkin RJ;Ficicioglu C;Tanpaiboon P;Craigen WJ;Rosenberg AS;Kishnani PS
To assess the magnitude of benefit to early treatment initiation, enabled by newborn screening or prenatal diagnosis, in patients with cross-reactive immunological material (CRIM)-negative infantile Pompe disease (IPD), treated with enzyme replacement therapy (ERT) and prophylactic immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG. A total of 41 CRIM-negative IPD patients were evaluated. Amongst patients who were treated with ERT+ITI (n=30), those who were invasive ventilator-free at baseline and had ≥6 months of follow-up were stratified based on age at treatment initiation: 1) early (≤4 weeks), 2) intermediate (>4 and ≤15 weeks), and 3) late (>15 weeks). A historical cohort of 11 CRIM-negative patients with IPD treated with ERT monotherapy served as an additional comparator group. Twenty patients were included; five, seven, and eight in early, intermediate, and late treatment groups, respectively. Genotypes were similar across the three groups. Early-treated patients showed significant improvements in left ventricular mass index, motor and pulmonary outcomes, as well as biomarkers creatine kinase and urinary glucose tetrasaccharide, compared to those treated later. Our preliminary data suggest that early treatment with ERT+ITI can transform the long-term CRIM-negative IPD phenotype, which represents the most severe end of the Pompe disease spectrum.
