Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

Deprescribing Strategies: A Prospective Study on Proton Pump Inhibitors.

Proton pump inhibitors (PPIs) are among the most controversially prescribed drugs in polypharmacy. This observational prospective study assessed the PPI prescriptive trend during hospitalization before and after implementation of a prescribing/deprescribing algorithm in a real-life hospital setting and the related clinical-economic benefit at discharge. PPI prescriptive trends were compared between three quarters of 2019 (9 months) and the same period of 2018 by a chi-square test with a Yate's correction. The proportions of treated patients in the two years (1120 discharged patients in 2018 and 1107 in 2019) were compared by the Cochran-Armitage trend test. DDDs (defined daily doses) were compared between 2018 and 2019 by the non-parametric Mann-Whitney test and normalizing DDD/DOT (days of therapy) and DDD/100 bd (bed days) for each patient. Multivariate logistic regression was performed on PPI prescriptions at discharge. The distribution of patients with PPIs at discharge was significantly different in the two years (p = 0.0121). There was a downward trend in the number of PPI prescriptions (29.9%) in the third trimester of 2019 compared to the others of the same year (first trimester: 34.1%, second trimester: 36.0%) and by contrast with the same periods of 2018 (29.4, 36.0, and 34.7%) (p = 0.0124). DDDs/patient did not differ between 2018 and 2019 nor across the three trimesters. However, both DDD/DOT and DDD/100 bd showed a decrease in the third trimester of 2019, with a marked difference for DDD/DOT (p = 0.0107). The reduction in consumption detected in the last phase of 2019 in terms of DDD/DOT was 0.09 with a consequent containment of pharmaceutical spending. The development and implementation of multidisciplinary prescribing/deprescribing protocols in both hospital and community settings could lead to a reduction in the misuse of PPIs, with significant savings in healthcare resources.