Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma.

BACKGROUND: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. OBJECTIVE: To compare global differences in ease of access to biologics. METHODS: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. RESULTS: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/µL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. CONCLUSIONS: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world.

Implementation of a protocol for management of antepartum iron deficiency anemia: a prospective cohort study.

BACKGROUND: In randomized trials, antepartum intravenous iron sucrose is effective at improving predelivery hemoglobin in iron deficiency anemia. Yet, there is a gap between this knowledge and its implementation into care. OBJECTIVE: We aimed to determine if the implementation of a standardized protocol for the management of antepartum anemia outside of a clinical trial improves intravenous iron sucrose utilization and clinical outcomes. STUDY DESIGN: We performed a prospective cohort study evaluating the incorporation of an anemia protocol into routine clinical care for women with antepartum hemoglobin <11.0 g/dL. Our protocol, developed with multidisciplinary stakeholders, included (1) serial third trimester hemoglobin assessment, (2) oral iron supplementation for antepartum hemoglobin 9.5-11 g/dL, and (3) antepartum intravenous iron sucrose use (300 mg weekly for 3 weeks) for hemoglobin <9.5 g/dL. We compared 6-months preimplementation (January 2018 to June 2018) to 6-months postimplementation (January 2019 to June 2019). The outcomes evaluated were antepartum intravenous iron sucrose utilization, the number of intravenous iron sucrose dosages, predelivery hemoglobin, and blood transfusion. RESULTS: A total of 1423 women were included (pre=778; post=645) without significant baseline differences. The antepartum hemoglobin nadir was no different between the groups (pre: 10.2; interquartile range [9.6-10.6] vs post: 10.2; interquartile range [9.6-10.6]; P=.77). The implementation of a standardized protocol for the management of antepartum anemia was associated with 80% increased odds of receiving intravenous iron sucrose than the preimplementation group (pre: 4.8% vs post: 8.2%, P=.008; odds ratio, 1.79; 95% confidence interval, [1.16-2.77]). The implementation of a standardized protocol for the management of antepartum iron deficiency anemia was also associated with higher hemoglobin at admission for delivery (pre: 10.9; interquartile range [10.1-11.6] vs post: 11.0; interquartile range [10.3-11.7], P=.048). There were no significant differences between the groups in blood product transfusion (pre: 7.1% vs post: 5.1%, P=.13). CONCLUSION: Implementation of a standardized antepartum anemia protocol is associated with increased intravenous iron sucrose utilization and improvement in predelivery hemoglobin.

Traditional Therapies for Severe Asthma.

Severe asthma is a complex and heterogeneous disease. The European Respiratory Society and American Thoracic Society guidelines define severe asthma for patients 6 years or older as "asthma which requires treatment with high-dose inhaled corticosteroids…plus a second controller or systemic corticosteroids to prevent it from becoming 'uncontrolled' or which remains 'uncontrolled' despite this therapy." This article reviews available traditional therapies, data behind their uses in severe asthma, and varying recommendations. As various asthma endotypes and phenotypes are better understood and characterized, targeted therapies should help improve disease outcomes, efficacy, and cost-effectiveness.

Performance of lecithin-sphingomyelin ratio as a reflex test for documenting fetal lung maturity in late preterm and term fetuses.

OBJECTIVE: To determine if infants delivered after immature or indeterminate TDx-FLM II testing and a mature reflex test are at increased risk for neonatal respiratory complications. METHODS: The primary analysis compared neonatal respiratory morbidity (RDS or TTN) in 34-39-week fetuses delivered after either (i) mature TDx-FLM II testing, or (ii) indeterminate or immature TDx-FLM II and a positive reflex test (PG or L/S ratio). RESULTS: Fifty patients delivered after mature TDx-FLM II, and 30 after immature or indeterminate TDx-FLM II with an L/S ≥ 2.0. Respiratory morbidity was significantly higher in the group delivered after mature reflex testing compared with mature TDx-FLM II (23% vs. 2%, p < 0.01). When PG was present, there were no cases of RDS or TTN. CONCLUSIONS: Utilizing L/S ratios as a reflex test to confirm lung maturity was associated with a high risk for respiratory morbidity, particularly when PG was not present.