Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

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.

Expression of keratin 17 in proliferative skin diseases / 中华皮肤科杂志

Objective To investigate the expression and significance of keratin 17 (K17) in proliferative skin diseases,including psoriasis,basal cell carcinoma (BCC),squamous cell carcinoma (SCC) and malignant melanoma.Methods Tissue specimens were collected from the lesions of 14 patients with severe plaque-type psoriasis,16 patients with BCC,16 patients with SCC,8 patients with malignant melanoma,as well as from the normal skin of 17 patients with trauma.Immunohistochemistry was conducted to detect the expression of K17 in these tissue samples.Results K17 was absent in the cytoplasm of keratinocytes in the basal layer,prickle cell layer or granular layer of the normal skin.There was a strong expression of K17 in the prickle cell layer,but a weak or negative expression of K17 in the basal layer of psoriatic skin,and parakeratotic cells did not express K17.In BCC tissues,K17 was absent in carcinoma cells,but visible in peritumoral cells in the prickle cell layer and granular layer.In SCC tissues,K17 was localized in highly differentiated carcinoma cells,but not in lowly differentiated carcinoma cells.There was a strong expression of K17 throughout the epidermis above the melanoma,but a negative expression in the melanoma cells or melanocytes.Conclusion K17 may serve as a molecular marker for the differential diagnosis of some proliferative skin diseases.

Expression of activin receptor-like kinases 1 in dermal fibroblasts from patients with systemic scleroderma and its roles / 中华皮肤科杂志

Objective To measure the expression of activin receptor-like kinases 1(ALK1)in dermal fibroblasts from patients with systemic scleroderma(SSc)and to estimate its role in the production of fibronectin and plasminogen activator inhibitor-1(PAI-1).Methods Dermal fibroblasts were isolated from the lesions of 12 patients with SSc as well as the normal skin of 14 healthy controls,and subjected to a primary culture.The third-passage fibroblasts were used in the next experiment.Western blot and indirect immunofluorescence technique were utilized to quantify the expression of ALK1.A specific siRNA targeting ALK1 was designed,constructed,and transiently transfected into the control dermal fibroblasts,which were then classified into 2 groups to be cultured with or without the presence of transforming growth factor(TGF)-β1 for 72 hours followed by the detection of fibronectin and PAI-1 expression with Western blot.Results As Western blot and direct immunofluorescence technique showed,both control and SSc fibroblasts showed an expression of ALK1 in the cytoplasm and membrane,and the expression intensity of ALK1 in SSc fibroblasts was significantly higher than that in the control fibroblasts(1.97 ± 0.05 vs.1.12 ± 0.03,t =50.96,P ＜ 0.05).The expression of ALK1,fibronectin and PAI-1 was decreased by 90％,58％ and 31％ respectively in specific siRNA-transfected SSc fibroblasts compared with the control siRNA-transfected fibroblasts.TGFβ1 significantly increased the expression of ALK1,fibronectin and PAI-1 in the control siRNA-transfected fibroblasts,but the increase was markedly inhibited by the siRNA-targeting ALK1.Conlusion TGFβ1 can promote the production of fibronectin and PAI-1 via ALK1 in fibroblasts,and ALK1 may be involved in the development of sclerosis in SSc.

The Evaluation of Organ Damage in Systemic Lupus Erythematosus / 中华皮肤科杂志

Objective To study the organ damage in patients with systemic lupus erythematosus (SLE) and its significance in prognosis. Methods The SLE damage index (SDI) was used to evaluate 121 female and 15 male patients. Results Among these patients, the lowest and the highest SDI was 0 or 9, separately (average: 1.79 ? 2.22). Most damaged organ was renal (39.0%), followed by muscle/skeletal system (19.9%) and cardiovascular system (18.4%). There was statistically significant difference of SDI in different groups of prognosis, life condition or disease duration ( 10 years). However, there was no significant difference of SDI in different sex groups. The correlation analysis revealed that the age at onset or diagnosis was not related to SDI. Conclusion SDI is effective in evaluating the organ damage in predicting prognosis of SLE patients.

The Significance of Systemic Lupus Erythematosus Disease Activity Index in the Treatment of SLE / 中华皮肤科杂志

Objective To study the clinical significance of systemic lupus erythematosus disease activity index(SLEDAI) in the treatement of SLE. Methods Disease activity of every patient with SLE 10 days before admission and before discharging was assessed using the SLEDAI system. The patients were treated separately with prednisone, pulse methylprednisolone and/or pulse cyclophosphamide according to their conditions. Statistical analysis was carried out using SPSS software. Results ①The difference of SLEDAI between the patients before admission and discharging was significant (P