Reduced immune functioning may have a negative impact on sleep and health, and vice versa. A survey among Dutch young adults (18–35 years old) was administered to collect information on perception of reduced immunity and its relationship to sleep disorders, sleep duration, and quality. Sleep disorders were assessed with the SLEEP-50 questionnaire subscales of sleep apnea, insomnia, circadian rhythm disorder, and daily functioning. Dutch young adults (N = 574) completed the survey. Among them, subjects (N = 209; 36.4%) reported perceived reduced immunity. Relative to those with a normal immune status, subjects reporting reduced immunity had significantly higher scores (p = 0.0001) on sleep apnea (2.6 versus 3.6), insomnia (5.1 versus 6.8), and circadian rhythm disorder (2.1 versus 2.7). Subjects reporting reduced immunity also had significantly poorer daily functioning scores (5.4 versus 7.6, p = 0.0001). No differences were observed in total sleep time, but those reporting reduced immunity had significantly poorer ratings of sleep quality (6.8 versus 7.2, p = 0.0001). Our findings suggest that perceived reduced immunity is associated with sleep disturbances, impaired daily functioning, and a poorer sleep quality. Experimental studies including the assessment of immune biomarkers and objective measures of sleep (polysomnography) should confirm the current observations.

Introduction Emicizumab is an effective new treatment option for people with hemophilia A (PwHA). The approved dosing regimens are based on body weight, without the necessity for laboratory monitoring. This assumes a clear dose-concentration-response relationship, with acceptable variability due to factors other than body weight. To investigate this assumption, a systematic review on the pharmacokinetics (PK) and associated efficacy of emicizumab in humans was conducted. Methods The EMBASE, Pubmed and CENTRAL databases were systematically searched to November 2020 to identify studies on the PK data of emicizumab in humans. Data on the study, population, PK and efficacy (annualized bleeding rate of treated [joint] bleeds) were extracted and synthesized, and exposure effects modeling was performed using non-linear least squares regression in a maximum effect (E max ) model. ResultsThe 15 included studies reported on data for 140 volunteers and 467 PwHA, including children (0 to <12 years) and adolescents and adults (≥12 years), both with and without factor VIII (FVIII) inhibitors. Emicizumab demonstrated dose-linear PK. The interindividual variability of trough concentrations was moderate (32%) and was similar across various subgroups, such as FVIII inhibitor status, age group and dosing interval. The control of bleeds did not further improve above emicizumab concentrations of 30 µg/mL, potentially enabling lower dosing in a substantial proportion of PwHA. Conclusion This review supports body weight-based dosing, although individualized monitoring of emicizumab concentrations may allow for more cost-effective dosing.

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