ABSTRACT
BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.
Subject(s)
Adult , Humans , Dermatitis, Atopic/drug therapy , Treatment Outcome , Severity of Illness Index , Antibodies, Monoclonal, Humanized/therapeutic use , Injections, Subcutaneous , Double-Blind MethodABSTRACT
BACKGROUND:Animal and cel studies have shown that the Kidney Recipe can prevent and treat osteoporosis and improve bone metabolism, but this recipe is complicated. Recent studies on compound Chinese medicine mainly focused on serum drug metabolism and pharmacokinetics, which has limitations, and the effective ingredient and pharmaceutical material basis are uncertain. OBJECTIVE:In the different concentrations and time, by using different compatibility proportion of active ingredients of Kidney Recipe, osteoblasts from neonatal Sprague-Dawley rats were subjected to culture intervention. The proliferation and differentiation of osteoblasts were determined so as to identify time-effect and dose-effect relationship of Kidney Recipe on osteoblasts and to provide experimental evidences for prevention and treatment of osteoporosis. METHODS:Primary neonatal 24-hour osteoblasts of Sprague-Dawley rats were cultured in vitro. Herbs“tonic”and“cathartic”active chemical components of different proportion were used. The experiment contained three groups:Tonics Medicine (T)>Cathartic Medicine (C) group, TC group and TC group (PC and TC group (PC group. At mass concentration of 20μg/L and 24 hours of culture, the promoting effect on alkaline phosphatase secretion was most significant in the TC group (PC group in the time-effect and the dose-effect relationship.
ABSTRACT
BACKGROUND:Chinese nourishing kidney herbs can prevent osteoporosis and improve bone metabolism, which has been proved in animal and cel experiments. But there are few reports on the compatibility of Chinese nourishing kidney herbs, and it is difficult to screen the optimal compatibility, as the interaction of active ingredients and drug substance basis are uncertain. OBJECTIVE: To determine the proliferation, differentiation and Smad4 mRNA expression of neonatal Sprague-Dawley rat osteoblasts cultured by Chinese nourishing kidney herbs with different compatibility so as to find out the optimal compatibility of Chinese nourishing kidney herbs. METHODS: Passage 5 osteoblasts were divided into five groups: group A, 1×10-5mol/L icarin; group B, 1×10-5mol/L icarin+1×10-5 mol/L naringin; group C, 1×10-5mol/L icarin+1×10-5 mol/L diosgenin; group D, 1×10-5mol/L icarin+ 1×10-5mol/L catalpol; group E, 10 μL normal saline (control group). There were six wels in each group. RESULTS AND CONCLUSION: Compared with the group E, the proliferative ability of osteoblasts and expression of Smad4 mRNA were increased in the groups B and C; until the 72nd hour, the proliferative ability of osteoblasts in the group B reached the peak. At 48 hours of culture, the activity of alkaline phosphatase in groups B and C was higher than that in group E; at 72 hours of culture, the activity of alkaline phosphatase in groups B and D was higher than that in group E. These findings indicate that the compatibility of Chinese nourishing kidney herbs can influence the activity of osteoblasts, and icarin+naringin has the strongest effect.