Chinese medicine Linggui Zhugan formula protects against diabetic kidney disease in close association with inhibition of proteinase 3-mediated podocyte apoptosis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Linggui-Zhugan (LGZG) comprises four herbs and is a classic formula in traditional Chinese medicine. There is strong clinical evidence of its pleiotropic effects in the prevention of diabetes and its related complications. Although several classes of drugs are currently available for clinical management of diabetic kidney disease (DKD), tight glycemic and/or hypertension control may not prevent disease progression. This study evaluated the therapeutic effect of the ethnopharmacological agent LGZG on DKD. AIM OF THE STUDY: This study aimed to investigate the effects of LGZG formula with standard quality control on experimental DKD and its related metabolic disorders in animal model. Meanwhile, the present study aimed to investigate regulatory effects of LGZG on renal proteinase 3 (PR3) to reveal mechanisms underlying renoprotective benefits of LGZG. MATERIALS AND METHODS: LGZG decoction was fingerprinted by high-performance liquid chromatography for quality control. An experimental model of DKD was induced in C57 BL/6J mice by a combination of high-fat diet feeding, uninephrectomy, and intraperitoneal injection of streptozocin. The LGZG decoction was administrated by daily oral gavage. RESULTS: Treatment with LGZG formula significantly attenuated DKD-like traits (including severe albuminuria, mesangial matrix expansion, and podocyte loss) and metabolic dysfunction (disordered body composition and dyslipidemia) in mice. RNA sequencing data revealed a close association of LGZG treatment with marked modulation of signaling pathways related to podocyte injury and cell apoptosis. Mechanistically, LGZG suppressed the DKD-triggered increase in renal PR3 and podocyte apoptosis. In-vitro incubation of mouse immortalized podocytes with LGZG-medicated serum attenuated PR3-mediated apoptosis. CONCLUSION: Our data demonstrated that the LGZG formula protected against DKD in mice and was closely associated with its inhibitory effects on PR3-mediated podocyte apoptosis.

A Retrospective Cohort Analysis of Treatment Patterns Over 1 Year in Patients with Psoriasis Treated with Ixekizumab or Guselkumab.

INTRODUCTION: Persistence and adherence to psoriasis treatments reflect overall drug effectiveness, tolerability, and convenience. Limited data are available on the treatment patterns of ixekizumab, an interleukin (IL)-17A antagonist, vs. guselkumab, an IL-23 inhibitor. Our objective was to evaluate real-life psoriasis drug treatment patterns with ixekizumab vs. guselkumab. METHODS: This retrospective observational study used United States insurance claims data from IBM Watson MarketScan Databases to analyze treatment patterns (including adherence, persistence, time on monotherapy, switching, and use of concomitant medications) for patients with 1 year, ≥ 6 months, and up to 30 months of follow-up. Outcomes were compared between ixekizumab and guselkumab on the balanced sample after applying inverse probability of treatment weighting (IPTW). RESULTS: Data for 1414 eligible patients (ixekizumab, N = 674 and guselkumab, N = 740) were assessed. Over the 1-year follow-up, adherence was greater for ixekizumab vs. guselkumab when evaluated by proportion of days covered ≥ 80% [odds ratio (OR) 1.77 (95% confidence interval, 1.41, 2.21), p < 0.001] and by medication possession ratio ≥ 80% [OR = 1.92 (1.54, 2.38), p < 0.001]. Persistence was longer for ixekizumab vs. guselkumab with a 60-day allowable gap [non-persistence hazard ratio (HR) (95% confidence interval): 0.80 (0.69, 0.93), p = 0.005], but there were no differences with a 90-day allowable gap [HR = 0.98 (0.83, 1.17), p = 0.850]. Results assessed in patients with ≥ 6 months follow-up confirmed these findings. This retrospective analysis of a United States claims database used prescription refill data to estimate persistence/adherence. CONCLUSIONS: Based on real-world evidence using claims data, patients with psoriasis treated with ixekizumab had a greater adherence to and an equal or greater persistence with therapy vs. patients treated with guselkumab.

In real-world settings, how consistently patients take a drug (adherence) and how long they continue taking it (persistence) are thought to reflect patients' satisfaction with the combination of efficacy and tolerability of the treatment. In this study of patients with psoriasis, we compared these measures­regularity of prescription refills and continued time on drug­between patients receiving ixekizumab or guselkumab for their psoriasis. This information was taken from a large insurance claims database, and so reflects results among commercially insured patients in the United States. We found that patients taking ixekizumab more consistently obtained prescription refills during the study period. Patients taking ixekizumab or guselkumab continued treatment for similar lengths of time when we allowed a longer gap of 90 days between prescription refills, but when a shorter gap of 60 days was allowed, those on ixekizumab spent a longer time on treatment. The findings were consistent regardless of prior treatment with other similar drugs (biologics). Overall, these findings indicate that for ixekizumab, which is dosed once every 4 weeks, and guselkumab, which is dosed once every 8 weeks, patients took ixekizumab more regularly and continued on the drug for about the same or a longer amount of time compared to patients taking guselkumab. These results may help dermatology practitioners in selecting biologic drugs for their patients with psoriasis.