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Matching-adjusted indirect treatment comparison of onasemnogene abeparvovec and nusinersen for the treatment of symptomatic patients with spinal muscular atrophy type 1.
Bischof, M, Lorenzi, M, Lee, J, Druyts, E, Balijepalli, C, Dabbous, O
Current medical research and opinion. 2021;(10):1719-1730
Abstract
OBJECTIVE Onasemnogene abeparvovec, a one-time intravenous gene replacement therapy, and nusinersen, an antisense oligonucleotide that requires ongoing intrathecal administration, have been evaluated as treatments for spinal muscular atrophy (SMA) type 1 in separate Phase III trials, but no head-to-head comparison studies have been conducted. Onasemnogene abeparvovec was compared with nusinersen using a matching-adjusted indirect comparison (MAIC) to estimate the treatment effect of onasemnogene abeparvovec relative to nusinersen for the treatment of symptomatic patients with SMA type 1 for up to 24 months of follow-up. METHODS In the absence of studies for both onasemnogene abeparvovec and nusinersen with a common comparator, a Bayesian naïve indirect treatment comparison (ITC) and MAIC between onasemnogene abeparvovec and nusinersen were conducted to compare efficacy and safety of onasemnogene abeparvovec with nusinersen. Outcomes of interest were event-free survival (EFS), overall survival (OS), and motor milestone achievements (independent sitting and independent walking). Relative treatment effects were expressed as relative risk (RR) and risk difference. RESULTS Pooled and weighted patient-level data illustrated a favorable effect toward onasemnogene abeparvovec, suggesting longer EFS for patients compared with nusinersen (HR of onasemnogene abeparvovec vs. nusinersen: 0.19 [95% CI: 0.07-0.54; 99% CI: 0.05-0.74]). At 24 months of follow-up, patients receiving onasemnogene abeparvovec were statistically significantly more likely to achieve the motor milestone of sitting independently compared with patients treated with nusinersen. Although statistically significant differences were not observed at 6 to 18 months between treatment options, the likelihood of sitting independently at 12 and 18 months numerically favored onasemnogene abeparvovec. A numerically greater likelihood of walking by 18 and 24 months was also observed for patients treated with onasemnogene abeparvovec compared with nusinersen. Onasemnogene abeparvovec therapy was also associated with a favorable (but statistically nonsignificant) outcome for OS and may be associated with prolonged survival compared with nusinersen (HR of onasemnogene abeparvovec vs. nusinersen: 0.35 [95% CI: 0.09-1.32; 99% CI: 0.06-2.01]). Bayesian naïve ITC results were similar to the MAIC analysis for EFS, OS, and motor milestone achievements. Small sample size limited covariate matching to baseline CHOP INTEND and nutritional support requirement, leading to wider CIs and statistically inconclusive outcomes for some of the results. CONCLUSIONS Despite limitations of the current MAIC analysis (mainly a small sample size for statistical testing, even for the pooled onasemnogene abeparvovec trials, and potential differences in prognostic and predictive factors between studies), the relative treatment effects in EFS, OS, and motor milestone achievement indicate that onasemnogene abeparvovec may offer continued benefit compared with nusinersen through 24 months of follow-up.
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Comparison of the Clinical Characteristics of Pneumocystis Pneumonia between Patients with Rheumatoid Arthritis Being Treated with Biologics and Those Being Treated without Biologics.
Akiyama, M, Kaneko, Y, Takeuchi, T
BioMed research international. 2017;:3710652
Abstract
OBJECTIVE The aim of this study was to compare the clinical characteristics of pneumocystis pneumonia (PCP) between patients with rheumatoid arthritis (RA) being treated with biologics and those being treated without biologics. METHODS From 8,630 patients with RA in our institution, we enrolled 24 patients who had developed PCP during the course of their treatment. They were divided into two groups according to the treatment they were receiving for RA: the biologics group (n = 12) and the nonbiologics group (n = 12). Clinical characteristics of PCP were compared between the two groups. RESULTS At PCP diagnosis, the biologics group showed significantly lower serum levels of β-D-glucan and C-reactive protein than the nonbiologics group, while the biologics group had significantly higher lymphocyte counts than the nonbiologics group. In the nonbiologics group, lower lymphocyte counts were associated with higher β-D-glucan levels; however, this was not observed in the biologics group. CONCLUSION The finding that RA patients being treated with biologics developed PCP with relatively normal lymphocyte counts and lower β-D-glucan levels suggests that the pathophysiology of PCP in those patients is different from that in patients being treated with other antirheumatic drugs.
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Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction.
Lu, Z, Kou, W, Du, B, Wu, Y, Zhao, S, Brusco, OA, Morgan, JM, Capuzzi, DM, , , Li, S
The American journal of cardiology. 2008;(12):1689-93
Abstract
Results of well-controlled prospective clinical trials showed the efficacy of lipid-lowering therapies in the reduction of cardiovascular (CV) events in western populations, but they were not reported with a Chinese population. This multicenter study was conducted to determine the effects of Xuezhikang (XZK), a partially purified extract of red yeast rice, on lipoprotein and CV end points in Chinese patients who experienced a previous myocardial infarction. Nearly 5,000 of these patients with average low-density lipoprotein cholesterol levels at baseline were randomly assigned either to placebo or to XZK daily for an average of 4.5 years. The primary end point was a major coronary event that included nonfatal myocardial infarction and death from coronary heart disease. Frequencies of the primary end point were 10.4% in the placebo group and 5.7% in the XZK-treated group, with absolute and relative decreases of 4.7% and 45%, respectively. Treatment with XZK also significantly decreased CV and total mortality by 30% and 33%, the need for coronary revascularization by 1/3, and lowered total and low-density lipoprotein cholesterol and triglycerides, but raised high-density lipoprotein cholesterol levels. In conclusion, long-term therapy with XZK significantly decreased the recurrence of coronary events and the occurrence of new CV events and deaths, improved lipoprotein regulation, and was safe and well tolerated.
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Selective medicated (normal saline and exogenous surfactant) bronchoalveolar lavage in severe aspiration syndrome in children.
Marraro, GA, Luchetti, M, Spada, C, Galassini, E, Giossi, M, Piero, AM
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2007;(5):476-81
Abstract
OBJECTIVE To study the ability of volume-controlled ventilation and medicated (normal saline plus surfactant) bronchoalveolar lavage in aspiration to reduce the duration of intubation and improve gas exchange. DESIGN : Randomized controlled clinical trial. SETTING Pediatric intensive care unit. PATIENTS Twenty children, 1 month to 16 yrs old, who were intubated and mechanically ventilated, were randomized within 6 hrs of aspiration to receive volume-controlled ventilation plus medicated bronchoalveolar lavage (treatment group) or the same ventilation and bronchosuction (control group). INTERVENTIONS Volume-controlled ventilation and positive end-expiratory pressure (10-12 cm H2O) were applied. Medicated bronchoalveolar lavage was performed using five aliquots of 5 mL of saline plus 10 mg/mL Curosurf (porcine surfactant, Chiesi Pharmaceutical SpA, Parma, Italy) in infants, five boluses of 10 mL of saline plus 5 mg/mL Curosurf in children, and four boluses of 25 mL of saline with 2.4 mg/mL Curosurf in adolescents for each affected lobe. One hour after bronchoalveolar lavage, 240 mg of Curosurf was administered locally. MEASUREMENTS AND MAIN RESULTS All patients survived. In the treatment group, days of intubation were 4.6 (+/-1.07), oxygenation index and Pao2/Fio2 improved significantly at 24 hrs, and statistical reduction in tidal volume mL/kg was observed from 36 hrs. In the control group, days of intubation were 11.8 (+/-3.22) (p < .0001), no improvement in oxygenation was noted, and pneumonia was observed in seven children (70%). CONCLUSIONS Even though this was an unblinded small clinical trial and low tidal volume strategy was not employed at an early stage after lung injury, there is some evidence that bronchoalveolar lavage with normal saline and surfactant may have clinical value in treating severe aspiration syndrome in children. More clinical studies are warranted to overcome study limitations and potential bias.
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Comparison of three treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome.
Baroutis, G, Kaleyias, J, Liarou, T, Papathoma, E, Hatzistamatiou, Z, Costalos, C
European journal of pediatrics. 2003;(7-8):476-480
Abstract
UNLABELLED The aim of the study was to compare the treatment regimen of three natural surfactants of different extraction and formulation (Alveofact [Surfactant A = SA], Poractant [Surfactant B = SB] and Beractant [Surfactant C = SC]) in neonatal respiratory distress syndrome (RDS). Premature infants of ≤32 weeks' gestation with birth weight of ≤2,000 g and with established RDS requiring artificial ventilation with a FiO2 ≥0.3 were randomly assigned to receive at least two doses of SA, SB or SC (100 mg/kg per dose). Infants who remained dependent on artificial ventilation with a FiO2 ≥0.3 received up to two additional doses. There were no differences among the groups regarding the necessity for more than two doses. The SA and the SB groups spent fewer days on a ventilator (p-value SA/SB 0.7, SA/SC 0.05, SB/SC 0.043) compared with the SC group, needed fewer days of oxygen administration (p-value SA/SB 0.14, SA/SC 0.05, SB/SC 0.04) and spent fewer days in hospital (p-value SA/SB 0.65, SA/SC 0.04, SB/SC 0.027). There were no statistically significant differences in the incidence of mortality, chronic lung disease, air leaks, necrotising enterocolitis, retinopathy of prematurity and intraventricular haemorrhage among the three groups. CONCLUSION The Alveofact and Poractant groups spent fewer days on the ventilator, needed fewer days of oxygen administration and spent fewer days in hospital compared with the Beractant group but no differences were observed among the three groups with regards to mortality and morbidity.