scholarly journals Long-term safety and effectiveness of velaglucerase alfa in Gaucher disease: 6-year interim analysis of a post-marketing surveillance in Japan

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Rieko Sagara ◽  
Masahide Ishigaki ◽  
Manami Otsuka ◽  
Kei Murayama ◽  
Hiroyuki Ida ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Interim Analysis ◽  
Gaucher Disease ◽  
Platelet Counts ◽  
Post Marketing Surveillance ◽  
Long Term Treatment ◽  
Post Marketing

Abstract Background Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering type 1, 2 or 3 GD.  Methods All patients with type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed.  Results In total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with type 2 GD. ADRs were reported by 63.6% (7/11) of patients with type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results.  Conclusion PMS data from patients with types 1–3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan. Trial registration: NCT03625882 registered July 2014.

Long-Term Safety and Effectiveness of Velaglucerase Alfa in Gaucher Disease: 6-Year Interim Analysis of A Post-Marketing Surveillance in Japan

2021 ◽  
Author(s):  
Rieko Sagara ◽  
Masahide Ishigaki ◽  
Manami Otsuka ◽  
Kei Murayama ◽  
Hiroyuki Ida ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Interim Analysis ◽  
Gaucher Disease ◽  
Platelet Counts ◽  
Post Marketing Surveillance ◽  
Long Term Treatment ◽  
Post Marketing

Abstract Background Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with Type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering Type 1, 2 or 3 GD. Methods All patients with Type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with Types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed. Results In total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with Type 2 GD. ADRs were reported by 63.6% (7/11) of patients with Type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results. Conclusion PMS data from patients with Types 1–3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan. Trial registration: NCT03625882 registered July 2014.

Long-term dutasteride therapy in men with benign prostatic hyperplasia alters glucose and lipid profiles and increases severity of erectile dysfunction

2017 ◽  
Vol 30 (3) ◽  
Author(s):  
Abdulmaged Traish ◽  
Karim Sultan Haider ◽  
Gheorghe Doros ◽  
Ahmad Haider
Keyword(s):  
Blood Glucose ◽  
Benign Prostatic Hyperplasia ◽  
Specific Antigen ◽  
Term Treatment ◽  
Prostatic Hyperplasia ◽  
Urinary Tract Symptoms ◽  
Long Term Treatment

AbstractBackgroundDutasteride has been successfully used in treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, dutasteride inhibits 5α-reductase type 1 and type 2 enzymes and may compromises glucocorticoids and androgen metabolism and alters metabolic function resulting in undesirable metabolic and sexual adverse side effects.AimThe aim of this study was to investigate the long-term adverse effects of dutasteride therapy in men with BPH on: i) blood glucose, ii) glycated hemoglobin (HbAMethodsA retrospective registry study, with a cohort of 230 men aged between 47 and 68 years (mean 57.78 ± 4.81) were treated with dutasteride (0.5 mg/day) for LUTS, secondary to BPH. A second cohort of 230 men aged between 52 and 72 years (mean 62.62 ± 4.65) were treated with tamsulosin (0.4 mg). All men were followed up for 36–42 months. At intervals of 3–6 months, and at each visit, plasma glucose, HbAResultsLong-term treatment with dutasteride therapy is associated with significant improvements in LUTS, as assessed by reduction in prostate volume, IPSS and prostate specific antigen (PSA). Long-term dutasteride therapy, however, resulted in increased blood glucose, HbAConclusionOur findings suggest that long-term dutasteride therapy produces worsening of ED, reduced T levels and increased glucose, HbA

scholarly journals Safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus and impaired renal function: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM)

2021 ◽  
Vol 24 (2) ◽  
pp. 141-155
Author(s):  
K. Tobe ◽  
H. Maegawa ◽  
I. Nakamura ◽  
S. Uno
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Impairment ◽  
Japanese Patients ◽  
Surveillance Study ◽  
Post Marketing Surveillance ◽  
Post Marketing

STELLA-LONG TERM, a 3-year post-marketing surveillance study, evaluated the safety and effectiveness of the sodiumglucose cotransporter 2 inhibitor ipragliflozin in Japanese type 2 diabetes mellitus (T2DM) patients. Final results in the safety (n = 6697) and effectiveness populations (n = 5625) were analyzed by stratifying patients by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) into four subgroups (≥90, 60 to <90, 45 to <60, and <45) and two subgroups (≥60 and <60). Adverse drug reaction (ADR) incidence, and changes from baseline in glycosylated hemoglobin (HbA1c), bodyweight, and eGFR were assessed. The percentage of patients experiencing ADRs and serious ADRs was similar across most eGFR subgroups. Polyuria/pollakiuria was the most common ADR. Renal disorders and volume depletion ADRs were more frequent in the subgroups with more severe renal impairment at baseline than in those with an eGFR of 60 to <90 or ≥90 mL/min/1.73 m2. Bodyweight and HbA1c decreased in all subgroups, the latter by − 0.91% to − 0.40% (P <0.05 vs. baseline). eGFR increased in the 45 to <60 mL/min/1.73 m2 subgroup (+ 1.42 ± 8.77 mL/min/1.73 m2; P = 0.006). It decreased in the ≥90 and 60 to <90 mL/min/1.73 m2 subgroups (− 8.27 ± 13.73 and − 1.22 ± 10.34 mL/min/1.73 m2; P <0.001), but not to <60 mL/min/1.73 m2. In conclusion, there were no new or unexpected safety findings in Japanese patients treated with ipragliflozin for T2DM, and long-term sustained improvements in HbA1c and bodyweight were observed regardless of the presence of renal impairment.

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