Safety and Efficacy of Empagliflozin in GSD1b Patients With Neutropenia (EMPAtia)

Evaluation of Efficacy and Safety of Empagliflozin in Treatment of Neutropenia in Patients With Glycogenosis Ib

Department of Internal Medicine, Hypertension and Vascular Diseases, The Medical University of Warsaw

Symptoms of glycogen storage disease type Ib (GSD Ib) include - among others - hypoglycemia, hepatomegaly and neutropenia with concomitant neutrophil dysfunction, which results in recurrent bacterial and fungal infections, and inflammatory bowel disease. At present filgrastim is the only available drug to treat neutropenia in GSD Ib patients; it stimulates neutrophil production, but doesn't restore their function. Part of GSD Ib patients doesn't respond to filgrastim treatment. The latest research results showed, that neutropenia and neutrophil dysfunction in GSD Ib patients are results of extensive accumulation of 1,5-anhydroglucitol-phosphate. Empagliflozin, a SGLT2 inhibitor, inhibits renal glucose and 1,5-anhydroglucitol reabsorption and is an effective and safe method of treatment of neutropenia in this group of patients. Empagliflozin (Jardiance®) is a drug, which is registered in Poland to treat type II diabetes in adults. The aim of our study is to evaluate the efficacy and safety of neutropenia in patients with GSD Ib with empagliflozin (Jardiance®).

who achieved >500 neutrophils/ml for at least 6 months with normalization of oxidative burst with decrease of bacterial and fungal infections compared to the period before study with decrease of hospitalization number with decrease of the number of defecation, gingival sores, and calprotectin average concentration in stool

measured as change of triglycerides (mg/dL), lactate (mg/dL), and uric acid (mg/dL) compared to the period before study

Inclusion Criteria: Minimum age 4 weeks old female Or Male GSD1b confirmed by genetic analysis with neutropenia and/or reduced respiratory burst Informed consent signed by the parents/assigns, and the recipient (>13 years old) Exclusion Criteria: Risk of non-compliance Chronic renal diseases (eGFR < 60 ml/min/1,73 m2) Active urinary tract infection (temporal criterion, up to recovery) Participation in another clinical trial (minimum 6 months from the end of participation until the date of signing the Informed Consent Form) Participation in therapeutic experiment, in addition to the experimental treatment with empagliflozin (minimum 12 months from the end of participation until the date of signing the Informed Consent Form) Pregnancy, breastfeeding Allergy to Empagliflozin Lack of informed consent