Real-life effectiveness of mepolizumab in severe asthma: a systematic literature review.

OBJECTIVE: The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma in randomized controlled trials is well established. Following approval of mepolizumab as add-on therapy for severe eosinophilic asthma in multiple regions worldwide, it is now important to determine its impact in real-world settings in which patients are not subject to stringent eligibility criteria. This systematic literature review assessed published evidence of clinical outcomes, safety, and healthcare resource use among patients with severe asthma receiving mepolizumab in real-world settings. DATA SOURCES: Searches were conducted in Embase, MEDLINE, and MEDLINE In-Process via Ovid. STUDY SELECTIONS: Eligible studies were observational, and enrolled ≥10 patients with asthma who received mepolizumab 100 mg subcutaneously. Data extracted included annualized exacerbation rate, mean daily oral corticosteroid (OCS) dose, proportion of patients using OCS, several measures of lung function, patient-reported asthma control and health-related quality of life (HRQoL), safety, and economic burden. RESULTS: Twenty-three articles (22 unique studies; 2,040 patients with severe asthma on mepolizumab) were identified. Mepolizumab use was associated with a reduction in annualized exacerbation rates (requiring OCS) of 54-97% (p < 0.05 in all studies), reduced mean/median daily OCS doses, and OCS discontinuation during follow-up (27-84% of patients). Improvements in lung function, asthma control, and HRQoL were also observed. The most commonly reported adverse events included headache and arthralgia; discontinuation of mepolizumab due to adverse events occurred in 0-10.6% of patients. CONCLUSION: Findings show that patients with severe asthma consistently demonstrate clinically relevant benefits with mepolizumab treatment in a real-world setting.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options.

BACKGROUND: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients. METHODS: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines. Systematic literature reviews were conducted to identify evidence from randomized controlled trials (RCTs) of chemotherapy for patients with previously untreated, unresectable, stage IV UC. Searches included congress databases and articles published between 1990 and 2018. In order to align with the latest treatment paradigms in first-line advanced UC, a focused literature search was conducted to identify evidence supporting immuno-oncology (IO) agents. RESULTS: For advanced UC, guidelines universally recommend cisplatin-based chemotherapy as first-line treatment for eligible patients and carboplatin-based regimens for those unfit to receive cisplatin. Despite the evaluation of a number of different cytotoxic regimens over the years, including triplet combinations, survival outcomes have not improved markedly with chemotherapy. Median overall survival with standard of care chemotherapy is ~13 months. Based on the results of single-arm, phase II studies, recent treatment guidelines have included atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD-1) as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1. However, emerging evidence from RCTs of IO agents, including both cisplatin-eligible and cisplatin-ineligible patients, suggest that survival times exceeding 20 months are possible. CONCLUSIONS: After having reached a plateau with chemotherapy, the treatment landscape for advanced UC is evolving. Survival outcomes for patients with advanced UC are improving with treatment modalities involving IO agents.

The impact of intra-abdominal pressure on perioperative outcomes in laparoscopic cholecystectomy: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic cholecystectomy involves using intra-abdominal pressure (IAP) to facilitate adequate surgical conditions. However, there is no consensus on optimal IAP levels to improve surgical outcomes. Therefore, we conducted a systematic literature review (SLR) to examine outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. METHODS: An electronic database search was performed to identify randomized controlled trials (RCTs) that compared outcomes of low, standard, and high IAP among adults undergoing laparoscopic cholecystectomy. A Bayesian network meta-analysis (NMA) was used to conduct pairwise meta-analyses and indirect treatment comparisons of the levels of IAP assessed across trials. RESULTS: The SLR and NMA included 22 studies. Compared with standard IAP, on a scale of 0 (no pain at all) to 10 (worst imaginable pain), low IAP was associated with significantly lower overall pain scores at 24 h (mean difference [MD]: - 0.70; 95% credible interval [CrI]: - 1.26, - 0.13) and reduced risk of shoulder pain 24 h (odds ratio [OR] 0.24; 95% CrI 0.12, 0.48) and 72 h post-surgery (OR 0.22; 95% CrI 0.07, 0.65). Hospital stay was shorter with low IAP (MD: - 0.14 days; 95% CrI - 0.30, - 0.01). High IAP was not associated with a significant difference for these outcomes when compared with standard or low IAP. No significant differences were found between the IAP levels regarding need for conversion to open surgery; post-operative acute bleeding, pain at 72 h, nausea, and vomiting; and duration of surgery. CONCLUSIONS: Our study of published trials indicates that using low, as opposed to standard, IAP during laparoscopic cholecystectomy may reduce patients' post-operative pain, including shoulder pain, and length of hospital stay. Heterogeneity in the pooled estimates and high risk of bias of the included trials suggest the need for high-quality, adequately powered RCTs to confirm these findings.

Does deep neuromuscular blockade during laparoscopy procedures change patient, surgical, and healthcare resource outcomes? A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Deep neuromuscular blockade may facilitate the use of reduced insufflation pressure without compromising the surgical field of vision. The current evidence, which suggests improved surgical conditions compared with other levels of block during laparoscopic surgery, features significant heterogeneity. We examined surgical patient- and healthcare resource use-related outcomes of deep neuromuscular blockade compared with moderate neuromuscular blockade in adults undergoing laparoscopic surgery. METHODS: We conducted a systematic literature review according to the quality standards recommended by the Cochrane Handbook for Systematic Reviews. Randomized controlled trials comparing outcomes of deep neuromuscular blockade and moderate neuromuscular blockade among adults undergoing laparoscopic surgeries were included. A random-effects model was used to conduct pair-wise meta-analyses. RESULTS: The systematic literature review included 15 studies-only 13 were analyzable in the meta-analysis and none were judged to be at high risk of bias. Compared with moderate neuromuscular blockade, deep neuromuscular blockade was associated with improved surgical field of vision and higher vision quality scores. Also, deep neuromuscular blockade was associated with a reduction in the post-operative pain scores in the post-anesthesia care unit compared with moderate neuromuscular blockade, and there was no need for an increase in intra-abdominal pressure during the surgical procedures. There were minor savings on resource utilization, but no differences were seen in recovery in the post-anesthesia care unit or overall length of hospital stay with deep neuromuscular blockade. CONCLUSIONS: Deep neuromuscular blockade may aid the patient and physician surgical experience by improving certain patient outcomes, such as post-operative pain and improved surgical ratings, compared with moderate neuromuscular blockade. Heterogeneity in the pooled estimates suggests the need for better designed randomized controlled trials.

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan.

BACKGROUND: Vedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC. OBJECTIVE: The aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective. METHODS: A hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually. RESULTS: Over a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated. CONCLUSION: Our analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan.

Survival benefit, disease progression and quality-of-life outcomes of abiraterone acetate plus prednisone versus docetaxel in metastatic hormone-sensitive prostate cancer: A network meta-analysis.

AIM: Androgen deprivation therapy (ADT) has long been the gold standard for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Clinical trials have demonstrated significant survival benefits when docetaxel (DOC) or abiraterone acetate (AA) and prednisone (P) are added to ADT, necessitating comparison of these combination treatments. METHODS: A systematic review of randomised controlled trials (RCTs) of AA-/ADT-/DOC-containing treatment regimens in newly diagnosed patients with high-risk and/or high-volume mHSPC identified three RCTs (LATITUDE, CHAARTED and GETUG-AFU 15). Network meta-analyses (NMAs) using fixed effects Bayesian methods were performed to compare relative benefits of each treatment on overall survival (OS), radiographic progression-free survival (rPFS) and quality of life (QoL) measured by the Brief Pain Inventory, and the Functional Assessment of Cancer Therapy-Prostate questionnaire. One trial, STAMPEDE, was assessed in exploratory OS analyses. RESULTS: The hazard ratio (HR) for OS ranged from 0.85 to 0.92, with the Bayesian probability of AA + P + ADT being better than DOC + ADT ranging between 72% and 87%. For rPFS, the HR ranged between 0.71 and 0.76 (Bayesian probability range: 93%-97%). Exploratory analyses including STAMPEDE found similar trends. AA + P + ADT also showed improved QoL compared with DOC + ADT for at least 1 year of therapy, with results being more pronounced at 3 months. CONCLUSION: Our findings suggest that AA + P + ADT is at least as effective as DOC + ADT in reducing the risk of death in men with mHSPC and better at preventing disease progression and improving QoL. The NMA provides useful insights to clinicians and other decision-makers on the relative efficacy of treatment options for men with mHSPC.

Methods Used in Economic Evaluations of Tuberculin Skin Tests and Interferon Gamma Release Assays for the Screening of Latent Tuberculosis Infection: A Systematic Review.

BACKGROUND: Latent tuberculosis infection (LTBI) provides a constant pool of new active tuberculosis cases; a third of the earth's population is estimated to be infected with LTBI. OBJECTIVE: The objective of this systematic review was to assess the quality and summarize the available evidence from published economic evaluations reporting on the cost-effectiveness of tuberculin skin tests (TSTs) compared with interferon gamma release assays (IGRAs) for the screening of LTBI. METHODS: An extensive systematic review of the published literature was conducted. A two-step process was adopted to identify relevant articles: information was extracted into evidence tables and then analyzed. The quality of the publications was assessed using a 10-item checklist specific for economic evaluations. RESULTS: Twenty-eight studies were identified for inclusion in this review. Most of the studies found IGRAs to be more cost-effective than TSTs; however, the conclusions from the studies varied significantly. Most studies scored highly on the checklist although only one fulfilled all the stipulated criteria. A wide variety of methodological approaches were documented; identified differences included the type of economic evaluation and model, time horizon, perspective, and outcomes measures. CONCLUSIONS: The lack of consistent methods across studies makes it difficult to draw any firm conclusions about the most cost-effective option between TSTs and IGRAs. This problem can be solved by improving the quality of economic evaluation studies in the field of LTBI screening, through adherence to quality checklists.