Sema Kalkan Uçar, Neslihan Önenli Mungan, Gülden Fatma Gökçay, Ayşe Çiğdem Aktuğlu Zeybek, Sebile Kılavuz, Seda Gunes, Fatih Kardaş, Pelin Teke Kısa, Kısmet Çıkı, Aynur Küçükçongar Yavaş, Ayça Burcu Kahraman, Merve Yoldaş Çelik, Ebru Canda, Deniz Kor, Meryem Karaca, Tanyel Zübarioğlu, Emine Genç, Havva Yazıcı, Fatma Derya Bulut, Şebnem Kılıç, Hanım Aghakishili, Fehime Erdem Karapınar, Ezgi Burgaç, Ertuğrul Kıykım, Alperen Elek, Nihal Kardaş, Ekrem Ünal, Tuba Hilkay Karapınar, Meryem Albayrak, Canan Albayrak, Ayşegül Ünüvar, Saskia B. Wortmann, Deniz Yılmaz Karapınar
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.