Efficacy and safety of MAS825 (anti-IL-1ß/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function.

MAS825, a bispecific IL-1ß/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1ß and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.

Wrist actigraphy.

To record sleep, actigraph devices are worn on the wrist and record movements that can be used to estimate sleep parameters with specialized algorithms in computer software programs. With the recent establishment of a Current Procedural Terminology code for wrist actigraphy, this technology is being used increasingly in clinical settings as actigraphy has the advantage of providing objective information on sleep habits in the patient's natural sleep environment. Actigraphy has been well validated for the estimation of nighttime sleep parameters across age groups, but the validity of the estimation of sleep-onset latency and daytime sleeping is limited. Clinical guidelines and research suggest that wrist actigraphy is particularly useful in the documentation of sleep patterns prior to a multiple sleep latency test, in the evaluation of circadian rhythm sleep disorders, to evaluate treatment outcomes, and as an adjunct to home monitoring of sleep-disordered breathing. Actigraphy has also been well studied in the evaluation of sleep in the context of depression and dementia. Although actigraphy should not be viewed as a substitute for clinical interviews, sleep diaries, or overnight polysomnography when indicated, it can provide useful information about sleep in the natural sleep environment and/or when extended monitoring is clinically indicated.