Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

BACKGROUND: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection. OBJECTIVE: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone. DESIGN: Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multinational, multicenter trial. PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: Intravenous ensovibep, 600 mg, or placebo. MEASUREMENTS: Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90. RESULTS: An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (n = 247) or placebo (n = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; P = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep). LIMITATION: The trial was prematurely stopped because of futility, limiting power for the primary outcome. CONCLUSION: Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. PRIMARY FUNDING SOURCE: National Institutes of Health.

Lifestyle and risk of follicular lymphoma: a systematic review and meta-analysis of observational studies.

PURPOSE: To investigate the relationship between follicular lymphoma (FL) risk and common modifiable lifestyle factors, specifically smoking, alcohol, body mass index (BMI), and hair dye use. METHODS: We performed a systematic review and meta-analysis of observational studies published prior to 01 January 2020. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science and the reference lists of original studies and review articles. We used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95% CI). RESULTS: Twenty-four cohort and ten case-control studies were eligible. Ten articles examined smoking, 11 alcohol, 13 BMI, and four hair dye use and risk of FL. The meta-estimate for current smoking was 1.11 (95% CI 0.92-1.35; I2 = 51%) and there was no significant dose-response per 5-year increase in duration (p-trend = 0.087). Current alcohol intake was inversely associated with FL risk (meta-RR 0.87, 95% CI 0.81-0.94; I2 = 0%) and there was a significant dose-response per 5 drinks/week increase in intake (p-trend = 0.008). There was no association with 5 kg/m2 increase in early adulthood BMI (meta-RR 1.05, 95% CI 0.91-1.20; I2 = 7%) or being overweight (meta-RR 0.99, 95% CI 0.92-1.07; I2 = 0%) or obese (meta-RR 1.08, 95% CI 0.99-1.17; I2 = 0%) as an adult. Hair dye use before 1980 was positively associated with FL risk (meta-RR 1.66, 95% CI 1.22-2.25; I2 = 55%) and no evidence of effect after 1980. CONCLUSION: We found consistent evidence of an inverse association between current alcohol intake and FL risk, and a significant increased risk with hair dye use before 1980. The evidence for smoking is heterogeneous, but most studies did not support an association. Further research is required to understand the mechanisms underlying these associations and the potential for prevention strategies.