Efficacy and Safety of Taliglucerase Alfa for the Treatment of Gaucher Disease: A 9-Year Experience

Abstract Gaucher disease (GD) is one of the most common lysosomal disorders, occurring in approximately 1 in 40,000 live births worldwide. Since 2014 enzyme replacement therapy (ERT) with taliglucerase alfa has been the treatment of choice for adult patients with GD in Brazil. The aim of this study was to evaluate the long-term efficacy and safety of taliglucerase alfa in a cohort of Brazilian patients treated at a referral center for inborn errors of metabolism. All patients who received at least one infusion of the enzyme at the study center were considered eligible to participate. Patients were followed for adverse reactions and events throughout the study period. Platelets, hemoglobin, chitotriosidase activity, bone marrow burden (BMB) score, bone mineral density, and the severity score index (SSI) were analyzed. For patients who were switched to taliglucerase alfa from imiglucerase, the same variables were compared before and after the switch. At 9-year follow-up, all parameters of interest had remained stable or improved. The overall rate of adverse events was lower than in other studies that evaluated long-term ERT with taliglucerase, and no serious adverse events were considered related to treatment. Based on our findings, ERT with taliglucerase alfa is an effective and safe approach for treatment of patients with GD.

Bone marrow burden score is not useful as a follow-up parameter in stable patients with type 1 Gaucher disease after 5 years of treatment.

INTRODUCTION: Gaucher disease (GD) is one of the most prevalent lysosomal disorders, with an estimated incidence of 1 in 40,000 live births worldwide. Skeletal involvement is one of the main features of GD, causing morbidity and impacting long-term quality of life in patients with type 1 GD. OBJECTIVES: To characterize bone marrow infiltration in patients with type 1 GD followed at the Gaucher Disease Referral Center of Porto Alegre, Brazil, and to assess whether the Bone Marrow Burden score (BMB) correlates with clinical or laboratory parameters. We also evaluated whether the BMB score is a suitable parameter for long-term follow-up of patients with type 1 GD. METHODS: All included patients underwent magnetic resonance imaging for BMB score calculation at baseline, 1 year, and every other year thereafter or as clinically indicated from 2012 to 2018. RESULTS: The BMB score tended to decrease during the first 5 years of treatment, at a rate of -1.08 points per year; after the 5-year mark, BMB tended to remain stable. CONCLUSIONS: The BMB score is useful for response monitoring in the first five years of treatment. We recommend that, after 5 years of treatment, MRI for BMB evaluation should only be performed in non-adherent patients or in those who develop symptoms of acute skeletal disease.

ESR1 rs9340799 is associated with endometriosis-related infertility and in vitro fertilization failure.

Estrogen receptor alpha has a central role in human fertility by regulating estrogen action in all human reproductive tissues. Leukemia inhibitory factor (LIF) expression, a cytokine critical for blastocyst implantation, is mediated by estrogen signaling, so we hypothesized that ESR1 gene polymorphisms might be candidate risk markers for endometriosis-related infertility and in vitro fertilization (IVF) failure. We included 98 infertile women with endometriosis, 115 infertile women with at least one IVF failure and also 134 fertile women as controls. TaqMan SNP assays were used for genotyping LIF (rs929271), MDM2 (rs2279744), MDM4 (rs1563828), USP7 (rs1529916), and ESR1 (rs9340799 and rs2234693) polymorphisms. The SNP ESR1 rs9340799 was associated with endometriosis-related infertility (P < 0.001) and also with IVF failure (P = 0.018). After controlling for age, infertile women with ESR1 rs9340799 GG genotype presented 4-fold increased risk of endometriosis (OR 4.67, 95% CI 1.84-11.83, P = 0.001) and 3-fold increased risk of IVF failure (OR 3.33, 95% CI 1.38-8.03, P = 0.007). Our results demonstrate an association between ESR1 rs9340799 polymorphism and infertile women with endometriosis and also with women who were submitted to IVF procedures and had no blastocyst implantation.