Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.

Neuropsychological, neuropsychiatric, and quality-of-life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study.

INTRODUCTION: We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). METHODS: Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. RESULTS: The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). DISCUSSION: PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

Retroperitoneal versus direct femoral artery approach for thoracic endovascular aortic repair access: a case-control study.

BACKGROUND: Many individuals who are candidates for thoracic endovascular aortic repair (TEVAR) are found to have iliac artery anatomy and/or disease that preclude transfemoral endovascular access and require retroperitoneal surgical approach through more proximal arteries. This relatively more invasive technique could potentially affect the procedural outcomes. This study compares the retroperitoneal with transfemoral access used for TEVAR in a single center. METHOD: In this study, 133 consecutive patients (96 men; mean age ± SD: 69.5 ± 14.7 years) who underwent TEVAR between 1994 and 2009 in a single center were retrospectively evaluated. The type of endovascular access was identified in all the patients. The basic demographics, access method, endograft type, 30-day morbidity and mortality rates, as well as procedure recordings including fluoroscopic and procedure duration, estimated blood loss, and duration of hospitalization were compared between the TEVAR procedures performed using a surgical retroperitoneal approach and those using the standard femoral access. RESULTS: Retroperitoneal access was used in 19 (14.3%; 13 women; mean age ± SD: 71 ± 12.2 years) and direct femoral access in 114 (85.7%; 24 women; mean age ± SD: 69 ± 15.4 years) patients. Two of the retroperitoneal accesses were obtained after failure of femoral approach. Techniques that were used included iliac artery conduit (seven patients), aortic artery conduit (eight patients), aortobifemoral artery graft conduit (one patient), and direct sheath introduction through the distal aorta (two patients) or common iliac artery (one patient). Retroperitoneal approach was used more frequently in women (35%) as compared with men (6%) (p = 0.0001). In all, 79% of the retroperitoneal approaches were associated with use of delivery sheath sizes larger than 24F (p = 0.049). TEVAR technical success was 100% with retroperitoneal and 97.3% with femoral access (p > 0.05). Thirty-day mortality rates were 0% and 8.8% and the rates of access artery injury were 5.3% and 4.4% in retroperitoneal and femoral access groups, respectively (p > 0.05). The incidence of retroperitoneal hematoma was significantly higher with retroperitoneal access (21% vs. 2.6%, p = 0.008). Additionally, retroperitoneal access was associated with significant increase in estimated blood loss and duration of hospitalization (p < 0.05). CONCLUSIONS: Type of access does not affect TEVAR success and the early mortality rate. Retroperitoneal approach is a valuable alternative technique in cases involving failed or impossible femoral access. However, this approach is associated with higher chances of retroperitoneal bleeding and longer procedural time and duration of hospitalization. Thoracic endografts with smaller delivery systems could minimize the need for this approach in the future.

Delayed aortic aneurysm enlargement due to endotension after endovascular abdominal aortic aneurysm repair.

Abdominal aortic aneurysm (AAA) enlarges after successful endovascular repair, because of persistent blood flow within the aneurysm sac, or endoleak. In the absence of detectable endoleak, AAA may still expand, in part because of persistent pressurization within the excluded aneurysm, or endotension. We report three patients who underwent successful endovascular AAA repair in whom postoperative surveillance showed aneurysm regression, yet delayed AAA enlargement without demonstrable endoleak developed in all three patients. Endotension was confirmed in all three patients at elective open conversion. Our study underscores the significance of endotension as a mechanism of delayed aneurysm enlargement after successful endovascular AAA repair.