Table 3 Enzyme replacement therapy: role in the variation of lyso-Gb1 plasma levels

Dekker et al. [37]

P, M

64 GD1 patients

Marked reduction of lyso-Gb1 levels were observed in most GD1 patients receiving ERT (imiglucerase or alglucerase)

Rolfs et al. [38]

R, single center

19 GD patients

Significant and rapid reductions in lyso-Gb1 levels over time after commencing ERT (lyso-Gb1 levels ranged from 50 to 250 ng/ml prior to ERT), with the most marked reductions occurring immediately after the start and within the first 6 months of ERT, with lyso-Gb1 values below 50 ng/ml achieved in most patients

Elstein et al. [47]

R

22 treatment-naïve GD patients

21 GD patients previously treated with imiglucerase

Lyso-Gb1 levels decreased 82.7% in treatment-naïve patients (from 323.2 ± 29.9 ng/mL at baseline to 60.4 ± 11.3 ng/mL at week 209) and 52.0% in previously-treated patients (from 81.8 ± 15.8 ng/mL at baseline to 52.8 ± 15.2 ng/mL at week 161)

In treatment-naïve patients, decreasing lyso-Gb1 levels were significantly correlated with increasing platelet counts at weeks 13, 25, and 53 (p = 0.0112, p = 0.0010, and p = 0.0171, respectively) and with decreasing spleen volumes at weeks 25, 101, and 209 (p = 0.0235, p = 0.0318, and p = 0.0093, respectively). No statistically significant correlations were observed between lyso-Gb1 levels and platelets counts or spleen volumes in previously-treated patients

Tylki-Szymańskaa et al. [41]

R

64 GD patients

The variable "disease biomarker level" was found dependent of the binary variable "treated with ERT or not"

Hurvitz et al. [48]

R

40 pediatric GD patients

Lyso-Gb1 levels were inversely correlated with platelet counts in untreated children (p = 0.002) and with hemoglobin levels in treated children (p = 0.01). Lyso-Gb1 levels increased in almost 50% of untreated children during follow-up, more commonly in younger children. The increase in lyso-Gb1 levels while receiving ERT, seen in 8 children, was partly associated with non-compliance and weight gain (> 15%) without dose adjustment

Murugesan et al. [39]

P, M

169 GD1 patients under treatment (155 on ERT and 14 on eliglustat)

The long-term response of chitotriosidase and lyso-Gb1 to ERT, calculated as mean elevations of ULN, showed chitotriosidase was increased 29.2xULN at year 1 and decreased to 15.6xULN after 3-years treatment, whereas lyso-Gb1 was increased 62.8xULN at year 1 and decreased to 20.2xULN by year 3

Arkadir et al. [70]

R

25 GD1 patients with homozygosis N370S treated with ERT

imiglucerase (n = 4)

velaglucerase alfa (n = 17) taliglucerase alfa (n = 4)

Plasma lyso-Gb1 levels decreased markedly in the whole cohort independent of drug type, along with an increase in both hemoglobin and platelet counts and a decrease in spleen volume

The decay in lyso-Gb1 levels after ERT followed an exponential curve. Determination of the half-life for normalization of plasma lyso-Gb1 levels and spleen volume showed that these were half-normalized after 15.4 months and 112 months, respectively. Notably, the calculated half-life of lyso-Gb1 was markedly shorter in patients treated with velaglucerase alfa than in those receiving imiglucerase or taliglucerase alfa (14.7 months vs. 17.6 months), a pattern also observed for the calculated decay half-life of spleen reduction (118 months vs. 138 months)

Dinur et al. [71]

R

135 adult patients with GD1 treated with ERT

imiglucerase (n = 41)

velaglucerase alfa (n = 73)

taliglucerase alfa (n = 21)

Longitudinal observations showed decreasing lyso-Gb1 values over time compared with starting values, with values plateauing at around 100 months (approximately 8 years) on treatment. A large inter- and intra-individual variation in lyso-Gb1 levels was identified for all three ERTs