Relationship between FEV1 decline and mortality in patients with bronchiolitis obliterans syndrome-a systematic literature review.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is one of the most severe complications and the leading cause of late mortality and morbidity after lung transplantation (LT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). No approved treatment for BOS is available. This review aimed to systematically identify and summarise the findings regarding the relationship between FEV1 decline and mortality in patients who developed BOS following LT or allo-HSCT. METHODS: A systematic literature search was performed in the Medline, Embase and Cochrane reviews databases. Of the 501 potential studies identified 25 met inclusion criteria and were analysed. RESULTS: Overall, 13 studies reported a relationship between FEV1 and mortality, and 12 studies reported both mortality and FEV1 results but did not investigate the relationship between them. There was heterogeneity in the analyses, which investigated the relationship between FEV1 decline and mortality across the studies in terms of levels of lung functioning, comparison to a control group, treatment, and statistical methodology; nevertheless, a clear and consistent increase in the risk of death associated with FEV1 decrease was seen in the analysed studies. CONCLUSIONS: The systematic literature review identified studies and findings that support a relationship between FEV1 and mortality, with a decrease in FEV1 being statistically associated with increased risk of death. Knowing that lower FEV1 levels are associated with higher mortality rates may help assess the condition of a patient with BOS and monitor future treatment effectiveness. However, more evidence is needed to further investigate this relationship and to verify its clinical usefulness.

Efficacy and Safety of Avatrombopag in Patients with Chronic Immune Thrombocytopenia: A Systematic Literature Review and Network Meta-Analysis.

INTRODUCTION: A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids. METHODS: A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs). RESULTS: The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed. CONCLUSION: In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.