Shifting Towards Empagliflozin First-Line Therapy in Glycogen Storage Disease Type Ib: A Nationwide Real-World Study
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Published on: April 16, 2019
Sema Kalkan Uçar1, Neslihan Önenli Mungan2, Gülden Fatma Gökçay3
1Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Türkiye.
Insights
Empagliflozin (EMPA) monotherapy effectively treats glycogen storage disease type Ib (GSDIb) clinical symptoms, reducing infections and IBD. While G-CSF combination therapy improves neutrophil counts, EMPA alone addresses neutrophil dysfunction and its consequences in GSDIb patients.
Area of Science:
- Metabolic disorders
- Hematology
- Immunology
Background:
- Glycogen storage disease type Ib (GSDIb) presents with neutrophil dysfunction and neutropenia, leading to complications like inflammatory bowel disease (IBD).
- Granulocyte-colony stimulating factor (G-CSF) can correct neutropenia but often fails to resolve clinical symptoms.
- Empagliflozin (EMPA) has shown promise in correcting neutrophil dysfunction and associated clinical issues in GSDIb.
Purpose of the Study:
- To evaluate the long-term, real-world effectiveness of empagliflozin (EMPA) as first-line monotherapy for GSDIb.
- To compare EMPA monotherapy with G-CSF monotherapy and combination therapy in pediatric and adult GSDIb patients.
- To assess clinical outcomes, including infections, hospital admissions, IBD, and weight gain, in different treatment groups.
Main Methods:
- A nationwide retrospective study involving 42 GSDIb patients (36 pediatric).
- Patients were categorized into four groups: EMPA first-line monotherapy (I), G-CSF monotherapy (II), EMPA plus G-CSF (III), and no treatment (IV).
- Pediatric patients were analyzed separately to evaluate treatment efficacy.
Main Results:
- EMPA first-line monotherapy (P-I) and EMPA plus G-CSF (P-III) significantly reduced infections, hospital admissions, and IBD frequency compared to G-CSF monotherapy (P-II) or no treatment (P-IV).
- Pediatric patients on EMPA first-line monotherapy (P-I) showed significantly improved weight gain.
- While EMPA monotherapy improved clinical symptoms of neutrophil dysfunction, only combination therapy (P-III) led to significant increases in absolute neutrophil count (ANC) and hemoglobin.
Conclusions:
- First-line empagliflozin (EMPA) monotherapy is effective in managing the clinical manifestations of neutrophil dysfunction in GSDIb.
- EMPA demonstrates significant clinical benefits even without a statistically significant rise in absolute neutrophil count (ANC).
- Combination therapy with G-CSF may be necessary for achieving significant improvements in ANC and hemoglobin levels in GSDIb patients.
Abstract:
Neutrophil dysfunction and neutropenia are burdensome findings in glycogen storage disease type Ib (GSDIb). Treatment with granulocyte-colony stimulating factor (G-CSF) often corrects neutropenia but fails to improve clinical symptoms like inflammatory bowel disease (IBD). Recently, empagliflozin (EMPA) was shown to correct the neutrophil dysfunction and its clinical consequences. It is increasingly used as first-line monotherapy, but long-term, real-world data are lacking. This nation-wide retrospective study investigated 42 GSD1b patients (36 children) treated with EMPA as first-line monotherapy and compared them with those receiving combination therapy with G-CSF and treatment-naïve patients (I:EMPA first-line monotherapy [n = 9]; II:G-CSF monotherapy [n = 7]; III:EMPA plus G-CSF [n = 16]; and IV: neither EMPA nor GCSF [n = 10]). Pediatric (P) patients were evaluated separately. In pediatric patients receiving EMPA as first-line monotherapy (P-I) and those with EMPA plus G-CSF (P-III), the frequency of infections, hospital admissions, and IBD was significantly lower than in patients receiving GCSF-monotherapy (P-II) or no treatment (P-IV). Additionally, significantly improved weight gain was observed in P-I. While clinical improvement related to correction of neutrophil dysfunction was seen with EMPA first-line monotherapy (P-I), significant improvement in absolute neutrophil count (ANC) and hemoglobin levels was only seen in P-III with additional G-CSF treatment. In three cases, EMPA was safely paused and subsequently resumed, for example, during pregnancy or liver transplantation. First-line EMPA monotherapy effectively corrects clinical symptoms of neutrophil dysfunction in GSD Ib patients, even in the absence of a statistically significant increase in ANC.
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