1. Treatment with eliglustat, a newly FDA-approved substrate reduction therapy for Type I Gaucher disease, decreased spleen size in this randomized, placebo-controlled trial of treatment-naive individuals.
2. Treatment with eliglustat improved hemoglobin levels, liver volume, and platelet count.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Type I Gaucher disease is an autosomal recessive lysosomal storage disorder. In Gaucher Disease, mutations in the GBA gene result in insufficient B-glucocerebrosidase production. The current standard of treatment is enzyme replacement therapy, however, a new medication, eliglustat, has just been approved by the FDA. Eliglustat is a substrate reduction therapy, and strongly inhibits glucosylceramide synthase, thereby reducing the level of substrate broken down by B-glucocerebrosidase.
This study was a placebo-controlled trial of treatment-naive adults 16 years or older with Type 1 Gaucher Disease. Participants were followed for 9 months and the primary outcome was change in spleen volume. At the 9-month point, individuals randomized to eliglustat had reduction in spleen volume of about 30% compared to the placebo group (p<0.001). There was also a statistically significant improvement in hemoglobin, liver volume, and platelet count in the eliglustat group. Strengths of this study include the randomized study design and stratification by spleen size. The weaknesses of this study were the relatively short follow-up, small sample size, and comparison to placebo as opposed to the standard of care. A longer trial comparing eliglustat to the standard of care and including individuals who have previously been treated with enzyme replacement therapy should be done.
In-Depth [randomized controlled trial]: This study randomized 40 treatment-naive adults with Type I Gaucher disease to receive eliglustat, a newly FDA-approved substrate replacement therapy, or placebo for 9 months. Patients were excluded if they had received substrate reduction therapy in the last 6 months or enzyme replacement therapy in the last 9 months. Thirty-nine patients completed the 9-month follow-up period. The primary outcome was change in spleen size. Subjects were stratified by spleen volume (≤20 vs. >20 times normal size). Mean spleen volume decreased by 27.8% in the eliglustat group (95%CI -32.57% to -22.97%) and increased by 2.26% (95%CI 2.54% to 7.06%) in the placebo group for an absolute difference of -30.03% (95%CI -36.82% to -23.24%). The eliglustat group also had statistically significant improvements in hemoglobin level (1.2 g/dL increase), liver volume (-6.6%), and platelet count (41% increase). No patients withdrew from the study due to an eliglustat-related adverse event.
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