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INTRODUCTION: Clofarabine monotherapy at a dose of 52 mg/m2 per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in patients aged 1-21 years after at least two prior regimens. To address a post-marketing requirement for additional evidence of the clinical benefit of clofarabine in its approved indication, a meta-analysis of patient-level data was conducted. METHODS: A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m2. The primary endpoint was complete remission (CR). Secondary endpoints were overall remission (OR, defined by CR or CR with either incomplete platelet recovery or incomplete neutrophil and platelet recovery), duration of response, overall survival (OS), and safety. RESULTS: A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m2; of them, 374 were aged < 22 years (pediatric population). Rates of CR and OR were 16% (95% confidence interval [CI] 7, 26) and 28% (95% CI 20, 37), respectively, in the pediatric population and 12% (95% CI 5, 21) and 21% (95% CI 13, 31) in the overall population. Median OS (evaluable in three studies in pediatric patients) was 3.7 months (95% CI 0.1, 31.4), reaching 10.1 months (95% CI 0.3, 68.9) for those achieving OR. Sensitivity analyses supported these findings. The most frequent grade 3-4 adverse events were liver abnormalities, anemia, diarrhea, and febrile neutropenia. CONCLUSION: In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Clofarabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Recidiva , Ensaios Clínicos como AssuntoRESUMO
AIM: To evaluate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus insulin degludec 100 U/mL (IDeg-100) in predefined (≥65 years) and post hoc (≥70 years) age groups of people with type 2 diabetes (T2D) in the BRIGHT trial. MATERIALS AND METHODS: BRIGHT was the first head-to-head randomized trial comparing Gla-300 and Deg-100 in insulin-naïve adults with T2D. In this subanalysis, endpoints were studied by predefined (≥65 years, N = 596/333) and post hoc (≥70 years, N = 768/161) age groups. RESULTS: Heterogeneity of treatment effect was observed for HbA1c reductions across the ≥70 years subgroups, but not across the ≥ 65 years subgroups, with greater HbA1c reductions with Gla-300 versus IDeg-100 in those 70 years or older (least squares mean -0.34% [95% confidence interval: -0.589% to -0.100%]). There was no significant heterogeneity of treatment effect for incidence and rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) hypoglycaemia across any age subgroups over 24 weeks, but numerically lower incidence and rates were consistently observed for Gla-300 versus IDeg-100 in the 65 years or older and 70 years or older age groups in the initial 12 weeks. CONCLUSIONS: Gla-300 may be a suitable treatment option in the growing population of older people with T2D. Further investigation is required to determine Gla-300 glycaemic benefits in high-risk populations without increasing the risk of hypoglycaemia.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Idoso , Glicemia , Pré-Escolar , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Lactente , Insulina Glargina/efeitos adversos , Insulina de Ação ProlongadaRESUMO
Basal insulin therapy often involves a compromise between achievement of glycaemic targets and avoidance of hypoglycaemia, dependent on how intensively insulin is titrated. In the Phase 3a EDITION 1, 2 and 3 studies, insulin glargine 300 U/mL (Gla-300) provided glycaemic control equivalent to that of insulin glargine 100 U/mL (Gla-100), with less hypoglycaemia in individuals with type 2 diabetes mellitus (T2DM). The current study evaluated the rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia over six months of treatment with Gla-300 or Gla-100 in the EDITION studies, as a function of HbA1c. Analysis was performed on patient-level data pooled from the three EDITION studies, and annualized hypoglycaemia rate as a function of HbA1c at Month 6 was fitted using a negative binomial regression model. Participants treated with Gla-300 experienced a consistently lower rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia as compared with those treated with Gla-100, regardless of HbA1c at Month 6. Results suggest that treatment with Gla-300 vs Gla-100 could allow individuals with T2DM to achieve equivalent glycaemic control with less hypoglycaemia.