Comparative Efficacy and Safety of Anti-Interleukin-5 Therapies and Placebo in Patients with Uncontrolled Eosinophilic Asthma:A Systematic Review and Meta-analysis of Phase 3 Trials

The overall efficacy and safety of anti-interleukin （IL）-5 therapies at currently recommended dosages and administration remain to be fully characterized. The present study was a meta-analysis of Phase 3 trials of the efficacy and safety of anti-IL-5 therapies at the currently recommended dosages and administration compared with placebo in patients with uncontrolled eosinophilic asthma. This meta-analysis complied with the PRISMA guidelines. The primary efficacy outcome was asthma exacerbation rate, and the primary safety outcomes included the incidence rates of all adverse events, asthma worsening, and injection site reactions. A subgroup analysis was also performed according to the type of anti-IL-5 agent. Pooled estimates are presented as rate ratios or relative risks （RRs） with 95% confidence intervals （CIs）. Analyses included intention-to-treat cases. Six randomized controlled trials of anti-IL-5 therapies met the inclusion criteria. The overall rate ratio for asthma exacerbation was 0.54 （95% CI 0.47-0.61）. The RRs （95% CIs） for the incidence of all adverse events, asthma worsening, and injection site reactions compared with placebo were 0.93 （0.89-0.96）, 0.63 （0.56-0.72）, and 1.59 （0.95-2.65）, respectively. The subgroup analysis revealed that the incidence of injection site reactions was significantly higher among mepolizumab- than placebo-treated patients, with an RR of 2.56 （95% CI 1.15-5.68）. These results suggest that anti-IL-5 therapies at the currently recommended dosages and administration are effective and generally well tolerated in patients with uncontrolled eosinophilic asthma. However, the occurrence of injection site reactions warrants specific attention, especially concerning mepolizumab administration

Comparative Efficacy and Safety of Lorlatinib and Alectinib for ALK-Rearrangement Positive Advanced Non-Small Cell Lung Cancer in Asian and Non-Asian Patients: A Systematic Review and Network Meta-Analysis

To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse events (G3-AEs). There were no significant differences between lorlatinib and alectinib in overall participants for both PFS (hazard ratio [HR], 0.742; 95% credible interval [CrI], 0.466–1.180) and OS (HR, 1.180; 95% CrI, 0.590–2.354). In the Asian subgroup, there were no significant differences in PFS between lorlatinib and alectinib (HR, 1.423; 95% CrI, 0.748–2.708); however, in the non-Asian subgroup, PFS was significantly better with lorlatinib than with alectinib (HR, 0.388; 95% CrI, 0.195–0.769). The incidence of G3-AEs in overall participants was significantly higher with lorlatinib than with alectinib (risk ratio, 1.918; 95% CrI, 1.486–2.475). These results provide valuable information regarding the safety and efficacy of lorlatinib in ALK-p ALK-inhibitor‒naïve advanced NSCLC. Larger head-to-head RCTs are needed to validate the study results

Comparative Efficacy of ALK Inhibitors for Treatment-Naïve ALK-Positive Advanced Non-Small Cell Lung Cancer with Central Nervous System Metastasis: A Network Meta-Analysis

Central nervous system (CNS) metastases and acquired resistance complicate the treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC). Thus, this review aimed to provide a comprehensive overview of brain metastasis, acquired resistance, and prospects for overcoming these challenges. A network meta-analysis of relevant phase III randomized controlled trials was performed to compare the efficacies of multiple ALK inhibitors by drug and generation in overall patients with ALK-p untreated advanced NSCLC and a subgroup of patients with CNS metastases. The primary endpoint was progression-free survival (PFS). Generation-specific comparison results showed that third-generation ALK inhibitors were significantly more effective than second-generation ALK inhibitors in prolonging the PFS of the subgroup of patients with CNS metastases. Drug-specific comparison results demonstrated that lorlatinib was the most effective in prolonging PFS, followed by brigatinib, alectinib, ensartinib, ceritinib, crizotinib, and chemotherapy. While lorlatinib was superior to brigatinib for PFS in the overall patient population, no significant difference between the two was found in the subgroup of patients with CNS metastases. These results can serve as a foundation for basic, clinical, and translational research and guide clinical oncologists in developing individualized treatment strategies for patients with ALK-p, ALK inhibitor-naive advanced NSCLC

A Long-acting Muscarinic Antagonist （LAMA） Added to an Inhaled Corticosteroid and Long-acting Beta-2 Agonist Versus LAMA Alone in Moderate-to-severe Chronic Obstructive Pulmonary Disease:A Systematic Review and Meta-analysis of Randomized Trials

We assessed the overall efficacy and safety of a long-acting muscarinic antagonist （LAMA） added to an inhaled corticosteroid （ICS） and long-acting beta-2 agonist （LABA） as a combination therapy （LAMA＋ICS/LABA） versus LAMA monotherapy in patients with chronic obstructive pulmonary disease （COPD）. The overall efficacy and safety of LAMA＋ICS/LABA versus LAMA in patients with COPD were assessed by a meta-analysis of randomized controlled trials （RCTs）. We identified LAMA＋ICS/LABA RCTs by searching PubMed, Scopus, and the Cochrane Library database. Primary efficacy outcomes were changes in forced expiratory volume in 1 second （FEV1.0） from baseline. Incidences of all adverse events （AAEs） were the primary safety outcomes. Pooled estimates are presented as mean differences （MDs） or risk ratios （RRs） with 95％ confidence intervals （CIs）. Analyses included intention-to-treat cases. Three LAMA＋ICS/LABA RCTs met the criteria for inclusion in this study. The MD, RRs, and their 95％ CIs regarding changes in FEV1.0 for LAMA＋ICS/LABA compared with those of LAMA were 0.08 （0.04 to 0.13）; RRs and 95％ CIs for AAEs of LAMA＋ICS/LABA compared with those of LAMA were 1.03 （0.82 to 1.29）. Conclusions: Pulmonary function was significantly improved in the LAMA＋ICS/LABA group with no significant increase in AAE risk. These results provide important analysis regarding the overall efficacy and safety of LAMA＋ICS/LABA in patients with COPD