Long-Term Outcomes of Enzyme Replacement Therapy in Indian Patients with Gaucher Disease - A Multicentric Study

To evaluate the short- and long-term clinical and laboratory outcomes of Enzyme Replacement Therapy (ERT) in Indian patients with Gaucher disease (GD) and to identify factors influencing the therapeutic response.

This retrospective, multicentre cohort study included 204 patients with confirmed GD across 13 Indian centres. Eligible participants had received at least one year of ERT and provided both baseline and follow-up data. Patients were stratified by splenectomy status. Longitudinal outcomes assessed over 1-5, 10, and 15 y included hemoglobin levels, platelet counts, liver and spleen volumes, chitotriosidase activity, bone pain, bone mineral density (BMD), and height/weight Z-scores. Subgroup analyses evaluated the impact of age at ERT initiation, GD subtype, genotype, and baseline disease severity.

Of the 204 patients, 173 were non-splenectomised and 31 were post-splenectomy; notably, 136 (66.7%) presented with the GD3 phenotype. The median age at symptom onset, diagnosis, and ERT initiation was 1.5 y, 2.6 y, and 4.3 y respectively. The p.L483P allele was the predominant variant in the cohort. Within the first 1-5 y of ERT, non-splenectomised patients demonstrated marked improvements in hematological parameters, organomegaly, biomarker activity, growth metrics, and bone pain. These improvements were sustained through 10-15 y, characterized by stabilized visceral parameters, persistently low biomarker levels, steady growth, and a low incidence of new skeletal complications. Early initiation of ERT was associated with a greater magnitude of hematological response as early as 1 y.

ERT facilitates rapid clinical and laboratory improvements within 1-5 y, with benefits sustained over 10-15 y in Indian GD patients. Despite significant diagnostic delays and the advanced stage of disease at presentation common in this population, long-term outcomes remain highly favourable. Early initiation of ERT is critical for optimizing treatment response and preventing irreversible sequelae.