Analysis of the Exposure?Response Relationship for Mesothelioma among Asbestos-Cement Factory Workers

Since the development of the 5-point verbal and 11-point numerical scales for measuring noise annoyance by the ICBEN Team 6, these scales have been widely used in socio-acoustic surveys worldwide, and annoyance responses have been easily compared internationally. However, both the top two categories of the 5–point verbal scale and the top three ones of the 11-point numerical scale are correspond to high annoyance, so it is difficult to precisely compare annoyance responses. Therefore, we calculated differences in day–evening–night-weighted sound pressure levels (Lden) by comparing values corresponding to 10% highly annoyed (HA) on Lden_%HA curves obtained from measurements in 40 datasets regarding surveys conducted in Japan and Vietnam. The results showed that the Lden value corresponding to 10% HA using the 5-point verbal scale was approximately 5 dB lower than that of the 11-point numerical scale. Thus, some correction is required to compare annoyance responses measured by the 5-point verbal and the 11-point numerical scales. The results of this study were also compared with those of a survey in Switzerland.

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Exposure–Response Analysis for Selection of Optimal Dosage Regimen of Anifrolumab in Patients With Systemic Lupus Erythematosus

Rheumatology ◽

10.1093/rheumatology/keab176 ◽

2021 ◽

Author(s):

Yen Lin Chia ◽

Linda Santiago ◽

Bing Wang ◽

Denison Kuruvilla ◽

Shiliang Wang ◽

...

Keyword(s):

Type I Interferon ◽

Drug Clearance ◽

Optimal Dosage ◽

Type I ◽

Efficacy And Safety ◽

Response Relationship ◽

Phase 3 ◽

Optimal Dosage Regimen ◽

Exposure Response ◽

Selection Of

Abstract Objectives The randomized, double-blind, phase 2 b MUSE study evaluated the efficacy and safety of the type I interferon receptor antibody anifrolumab (300 mg or 1000 mg every 4 weeks) compared with placebo for 52 weeks in patients with chronic, moderate to severe SLE. Characterizing the exposure–response relationship of anifrolumab in MUSE will enable selection of its optimal dosage regimen in two phase 3 studies in patients with SLE. Methods The exposure–response relationship, pharmacokinetics (PK), and SLE Responder Index (SRI[4]) efficacy data were analysed using a population approach. A dropout hazard function was also incorporated into the SRI(4) model to describe the voluntary patient withdrawals during the 1-year treatment period. Results The population PK model found that type I IFN test–high patients, and patients with a higher body weight, had significantly greater clearance of anifrolumab. Stochastic clinical simulations demonstrated that doses <300 mg would lead to a greater-than-proportional reduction in drug exposure owing to type I interferon alpha receptor–mediated drug clearance (antigen-sink effect, more rapid drug clearance at lower concentrations) and suboptimal SRI(4) responses with wider confidence intervals. Conclusions Based on PK, efficacy, and safety considerations, anifrolumab 300 mg every 4 weeks was recommended as the optimal dosage for pivotal phase 3 studies in patients with SLE.

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