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The aim of the present study was to assess the overall efficacy and safety of long-acting beta-2 agonist （LABA） and long-acting muscarinic antagonist （LAMA） combination therapies （LABA/LAMA） versus monotherapies or placebo in patients with chronic obstructive pulmonary disease （COPD）. The overall efficacy and safety of LABA/LAMA versus LABA, LAMA, or placebo in patients with COPD were assessed by meta-analysis of Phase 3 trials. Primary efficacy outcomes included changes in forced expiratory volume in 1 second （FEV10） from baseline and responder rates using St. George’s Respiratory Questionnaire （SGRQ）. The incidence of serious adverse events （SAEs） was the primary safety outcome. Pooled estimates are presented as standard mean differences （SMD）, odds ratios （ORs）, or risk differences （RDs） with 95% confidence intervals （CIs）. Eleven articles reporting on 13 randomized controlled trials of LABA/LAMA met the criteria for inclusion in the present study. Comparing LABA/LAMA with LAMA, LABA, and placebo, the SMD （95% CI） for a change in FEV10 from baseline was 0.08 （0.06-0.09）, 0.09 （0.07-0.11）, and 0.24 （0.19-0.30）, respectively; the corresponding ORs （95% CI） for changes in SGRQ score were 1.39 （1.24-1.57）, 1.39 （1.06-1.83）, and 1.80 （1.47-2.19）, respectively. The RDs （95% CIs） for SAEs with LABA/LAMA compared with LAMA, LABA, and placebo were −0.01 （−0.02, 0.00）, −0.01 （−0.03, 0.00）, and 0.01 （−0.01, 0.02）, respectively. Pulmonary function and health-related quality of life were significantly higher for LABA/LAMA, and the risk of SAEs did not increase significantly with combination therapy. These results indicate the overall efficacy and safety of LABA/LAMA in patients with COPD.

The safety and efficacy profiles of alectinib versus crizotinib for patients with previously untreated anaplastic lymphoma kinase （ALK）-positive advanced non-small cell lung cancer still remains to be elucidated. We compared the overall efficacies of alectinib and crizotinib for previously untreated ALK-positive advanced non-small cell lung cancer through a meta-analysis of randomized controlled trials. The primary outcome was progression-free survival （PFS）. Pooled estimates were calculated as hazard ratios with 95％ confidence intervals. Two studies on alectinib met the inclusion criteria for this meta-analysis. The hazard ratio （95％ confidence interval） of alectinib for PFS, relative to crizotinib, was 0.41 （0.28-0.60）, demonstrating a superior overall efficacy of alectinib over crizotinib, in terms of PFS.

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.

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.

We comparatively assessed the overall efficacies of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for previously untreated, EGFR mutation-positive, advanced non-small cell lung cancer in Asians through a meta-analysis of relevant phase-3 trials. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. Pooled estimates were calculated as hazard ratios (HRs) with 95% confidence intervals (CIs). Seven studies on EGFR-TKIs met the inclusion criteria for this study. The HRs and 95% CIs for OS and PFS for EGFR-TKIs, relative to chemotherapy, were 0.98 (0.77–1.24) and 0.32 (0.24–0.43), respectively. We found no difference in overall efficacy between EGFR-TKIs and chemotherapy in terms of OS, although the median PFS with EGFR-TKI was superior to that with chemotherapy among Asians with previously untreated, EGFR mutation-positive, advanced non-small cell lung cancer (UMIN ID: UMIN28424).

The aim of this study was to compare the adverse effect profiles of mepolizumab（MPZ）and benralizumab（BRZ）in adults with uncontrolled asthma. A network meta-analysis of phase 3 trials was conducted to compare the adverse effects of MPZ and BRZ in patients with uncontrolled asthma. The MEDLINE-PubMed, Scopus and the Cochrane library databases were searched to identify any relevant articles. The outcome measures of fatal adverse events, headache, and injection site reaction are presented as odds ratios（ORs）with 95％ confidence intervals（CIs）. The surface under the cumulative curve（SUCRA）for each outcome was also compared among MPZ, BRZ, and placebo treatments. Four randomized controlled trials of MPZ（100mg s/c every four weeks）（100-MPZ）or BRZ（30mg s/c every eight weeks）（30-BRZ）met the criteria for inclusion in the study. The ORs and 95％ CIs of 100-MPZ compared with BRZ for fatal adverse events, headache, and injection site reaction were 0.26（0.01-4.90）, 0.79（0.40-1.54）, and 2.32（0.79-6.80）, respectively. SUCRAs for 100-MPZ, 30-BRZ, and placebo were 0.8, 0.3, and 0.4 for fatal adverse events, 0.5, 0.1, and 0.8 for headache, and 0.0, 0.6, and 0.8 for injection site reaction, respectively. There were no significant differences in the incidence of fatal adverse events, headache, and injection site reaction between MPZ and BRZ treatment. However, the SUCRA values indicate an association between administration of BRZ and the occurrence of fatal adverse event or headache, or between administration of MPZ and the occurrence of injection site reaction. Moreover, the incidence odds of injection site reaction were significantly higher in the MPZ group than in the placebo group. Further analysis will be needed to clarify the details of safety profiles of these anti-IL-5 therapies.

Nivolumab has recently been approved as a second-line treatment for squamous and non-squamous advanced non-small cell lung cancers (NSCLC). However, no studies have statistically evaluated the adverse event profiles for nivolumab and conventional second-line agents, such as docetaxel. Thus, there is unmet medical need for statistical analysis comparing the adverse effects of nivolumab and docdetaxel in patients with advanced NSCLC. This meta-analysis evaluated the non-inferiority and superiority of the adverse event profiles for nivolumab and docetaxel in patients with previously-treated or refractory advanced NSCLC. The meta-analysis examined two phase 3 trials and compared the incidences of drug-induced adverse events for the nivolumab-treated and docetaxel-treated patient groups. The primary outcomes were the odds ratios (ORs) and 95% confidence intervals (CIs) for any adverse event, fatigue, nausea, decreased appetite, diarrhea, myalgia, anemia, alopecia, neutropenia, febrile neutropenia, and leukopenia. Compared to docetaxel, the adverse event profile for nivolumab was non-inferior and superior for any adverse event (OR, 0.27; 95% CI, 0.19-0.39), fatigue (OR, 0.44; 95% CI, 0.31-0.62), nausea (OR, 0.37; 95% CI, 0.25-0.54), decreased appetite (OR, 0.58; 95% CI, 0.39-0.87), diarrhea (OR, 0.29; 95% CI, 0.19-0.45), myalgia (OR, 0.18; 95% CI, 0.09-0.38), anemia (OR, 0.08; 95% CI, 0.04-0.16), alopecia (OR, 0.01; 95% CI, 0.00-0.06), neutropenia (OR, 0.01; 95% CI, 0.00-0.04), febrile neutropenia (OR, 0.02; 95% CI, 0.00-0.16), and leukopenia (OR, 0.04; 95% CI, 0.01-0.19). These results suggest that, compared to docetaxel, nivolumab may be better tolerated for managing advanced NSCLC.