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Objectives: The objective of the study is to investigate the relationships between Type 1 interferon (T1-IFN) signatures and clinical characteristics of lupus patients. Methods: We examined 49 new-onset lupus patients who were diagnosed between 1999 and 2017. The patients treated with >10 mg of prednisolone or hydroxychloroquine were excluded from this study. Serum T1-IFN signatures were revealed by a functional reporter assay and standardized by recombinant IFN-α. Patient backgrounds, clinical findings, and treatments were retrospectively extracted from their electrical medical records. Clinical data were also available, including SLE Disease Activity Index of SLE patients on admission. Results: T1-IFN signatures of lupus patients closely correlated with lupus disease activities, such as SLE Disease Activity Index-2K, white blood cell, C3 levels, and the titre of double-strand DNA antibody. We found fever and acute lupus dermatitis closely associated with T1-IFN signature. Conclusions: In lupus patients, fever and acute lupus dermatitis are good indicators of a strong T1-IFN signature. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to investigate the relationships between Type 1 interferon (T1-IFN) signatures and clinical characteristics of lupus patients., Methods: We examined 49 new-onset lupus patients who were diagnosed between 1999 and 2017. The patients treated with >10 mg of prednisolone or hydroxychloroquine were excluded from this study. Serum T1-IFN signatures were revealed by a functional reporter assay and standardized by recombinant IFN-α. Patient backgrounds, clinical findings, and treatments were retrospectively extracted from their electrical medical records. Clinical data were also available, including SLE Disease Activity Index of SLE patients on admission., Results: T1-IFN signatures of lupus patients closely correlated with lupus disease activities, such as SLE Disease Activity Index-2K, white blood cell, C3 levels, and the titre of double-strand DNA antibody. We found fever and acute lupus dermatitis closely associated with T1-IFN signature., Conclusions: In lupus patients, fever and acute lupus dermatitis are good indicators of a strong T1-IFN signature., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Mizoribine (MZR) is a novel selective inhibitor of inosine mono-phosphatasedehydrogenase that was developed in Japan. We previously re portedthe efficacy and safety of oral MZR pulse therapy, which is associated withelevated peak serum MZR levels, in selected patients with lupus nephritis.However, only limited information is avail able as yet on the optimal peakserum level of MZR that would yield an enhanced clinical efficacy without serious toxicity in patients with lupus nephritis. Methods: A total of 11 patients withclinicallystable lupus nephritis treated with oral MZR pulse therapy combined withlow-dose prednisolone were enrolled in the cross-sectional study. The peakserum concentrations of MZR (as determined by HPLC) and the serum anti-dsDNA antibody titers (as determined by ELISA) were examined in the patients in order to evaluate the correlation between these two parameters. The correlation between the dose of MZR (mg/kg) administered orally as a single daily dose and the peak serum level of the drug was also examined. In two of the patients, serial measurements of the changes in the peak serum levels of MZR and anti-dsDNA titers could be conducted over 10 months. Results: A significant in verse correlation (r = -0.596, p = 0.0116) was observed between the peak serum levels of MZR and the serum anti-dsDNA antibody titers in the study participants, while the dose of prednisolone remained unchanged. The peak level of MZR in the serum was significantly correlated with the single dose of MZR (r = 0.509, p = 0.0371). In the two patients in whom serial measurements were conducted, the first patient who showed a peak serum MZR level of less than 2.5-3.0 mg/ml eventually developed an in crease of the serum anti-dsDNA titer with lypocomplementemia and proteinuria. On the other hand, in the second patient who showed a peak serum MZR level in excess of 4.0 mg/ml, persistently low serum anti-dsDNA titers with normocomplementemia were observed. Conclusion: Although this study is only a preliminary study conducted on a small sample, we speculate from the results that a peak serum level of MZR of at least more than 2.5-3.0 mg/ml is necessary to achieve satisfactory clinical efficacy of the drug for the treatment of lupus nephritis. Further study is needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the safety, pharmacokinetics and pharmacodynamics of BI 655064 in healthy Chinese and Japanese subjects after administration of single doses of 80-240 mg and multiple dosing of 240 mg once weekly over 4 weeks., Methods: Two phase 1, double-blind, placebo-controlled studies were conducted (single-rising doses of BI 655064 in Chinese/Japanese male subjects [n = 12 per BI 655064 dose group] or repeated 240 mg BI 655064 in Chinese male subjects [n = 9]). Plasma samples were collected to investigate BI 655064 pharmacokinetics, pharmacodynamics (CD40 receptor occupancy [RO]) and immunogenicity, along with the safety and tolerability of BI 655064., Results: BI 655064 showed good overall tolerability following single-dose administration of 80-240 mg and repeated administration of 240 mg BI 655064 over 4 weeks. More Chinese subjects reported adverse events compared with Japanese subjects following single-dose administration (59.4% vs 3.1%). BI 655064 exhibited nonlinear, saturable kinetics, with higher doses resulting in slower apparent clearance (0.514-0.713 mL min -1 ), and disproportionately higher total exposure (AUC 0-inf ; 5610-7780 μg·h mL -1 ) and maximum plasma concentration (15 700-21 300 ng mL -1 ) with 240 mg BI 655064. Ninety percent inhibition of CD40 RO was achieved with doses ≥120 mg, and a direct relationship between BI 655064 plasma concentration and inhibition of CD40 RO was observed. Most subjects had a positive treatment-emergent antidrug antibody response., Conclusions: BI 655064 pharmacokinetic and safety profiles in East Asian male subjects were consistent with those observed in a Western population. No adjustments in the BI 655064 dosing recommendations are warranted for future clinical trials., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)