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.

Efficacy and safety of two prolonged therapeutic regimens in patients with plaque psoriasis after treatment with tazarotene/betamethasone dipropionate cream: a multicenter clinical observation / 中华皮肤科杂志

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

Near-infrared light combined with tacrolimus ointment for the treatment of facial glucocorticoid-dependent dermatitis: a randomized controlled trial / 中华皮肤科杂志

Objective To evaluate the efficacy and safety of near-infrared light combined with tacrolimus 0.1％ ointment in the treatment of facial glucocorticoid-dependent dermatitis.Methods A total of 68 patients with facial glucocorticoid-dependent dermatitis were enrolled from Department of Dermatology of Yantai Yuhuangding Hospital between December 2014 and December 2015,and randomly and equally divided into treatment group and combination group by a random number table.The treatment group was treated topically with tacrolimus ointment twice a day for 4 weeks.Besides the treatment with tacrolimus ointment,the combination group was irradiated with near-infrared light once a week for 4 sessions.After 4-week treatment,improvement in clinical manifestations such as itching and burning sensation was evaluated,so was the therapeutic effect.Results The combination group showed significantly higher response rate (85.3％ [29/34]) compared with the treatment group (61.8％ [21/34],x2 =4.84,P ＜ 0.05).Additionally,response rates for itching and burning sensation,erythema,scales and papules were all significantly higher in the combination group than in the treatment group (x2 =4.84,6.35,8.42 and 5.52,respectively,all P ＜ 0.05).Conclusion Near-infrared light combined with tacrolimus ointment is effective and safe for the treatment of facial glucocorticoid-dependent dermatitis.

Effect of sera from chronic urticaria patients with anti-Helicobacter pylori antibodies on the release of histamine by human mast cells / 中华皮肤科杂志

Objective To investigate the relationship between anti-Helicobacter pylori (Hp) antibodies and development of chronic urticaria (CU).Methods Fifty CU patients with positive 13C-urea breath test and anti-Hp antibodies,as well as 50 healthy human controls were recruited in this study.Serum samples were collected from all the subjects.The samples from the patients were subjected to tests for anti-high affinity IgE receptor (anti-FcεRI) and-IgE antibodies.Human mast cells (HMCs) were classified into several parts to be incubated with the sera of patients with CU,the sera of healthy controls with anti-IgE and-FcεRI antibodies respectively for 20 minutes.Those incubated with the sera of healthy controls without these antibodies served as the control.Subsequently,the levels of histamine released by HMCs were measured by enzyme-linked immunosorbent assay (ELISA).Results The sera of CU patients showed a stronger ability to activate HMCs to release histamine than those of healthy controls ((3.13 ± 0.93) μg/L vs (2.92 ± 0.75) μg/L,t =2.39,P ＜ 0.05).Anti-FcεRI antibodies were detected in 4 patients,and antiIgE antibodies in 3 patients.A significant increase was observed in the levels of histamine released by HMCs incubated with anti-FcεRI antibody-positive and anti-IgE antibody-positive patient-derived sera (t =4.82,6.34,respectively,both P ＜ 0.01),but not in those incubated with patient-derived sera only positive for anti-Hp antibodies (t =1.74,P ＞ 0.05) compared with those incubated with healthy control-derived sera.In comparison with the antibody-free healthy control-derived sera,those with anti-Hp IgG antibodies showed no significant effect on the release of histamines by HMCs (t =1.95,P ＞ 0.05),whereas those with anti-FcεRI antibodies and anti-IgE antibodies exhibited an obvious promoting effect (t =3.72,3.02,respectively,both P ＜ 0.01).Conclusions The anti-Hp antibodies appears to have no role in the pathogenesis of CU,but the presence of anti-FcεRI and anti-IgE antibodies may contribute to the initiation of CU in patients with Hp infection.

Correlations between interrelated autoantibodies and the development of chronic idiopathic urticaria / 中华皮肤科杂志

Objective To estimate the correlations between chronic idiopathic urticaria (CIU) development and interrelated autoantibodies,including anti-high affinity immunoglobulin E receptor (anti-FcεRI) antibody,anti-immunoglobulin E (anti-IgE) antibody,anti-Helicobacter pylori (HP) antibody and antithyroglobulin antibody (TGAb).Methods This study included 100 patients with CIU,100 patients with acute urticaria (AU) and 100 healthy controls.Autologous serum skin test (ASST) was performed and allergens were detected by fluorescence-based enzyme linked immunosorbent assay (ELISA) in each subject.Serum levels of total IgE,anti-FcεRI antibody,anti-IgE antibody,anti-HP antibody and TGAb were measured.Chi-square test,analysis of variance,and Wilcoxon rank sum test were conducted for statistical analysis.Results The positivity rate of ASST was 53％,12％ and 0 respectively in patients with CIU,patients with AU and healthy controls,respectively.Food or inhalant allergens were detected in 86％ of the patients with AU,but not detected in any of the patients with CIU or healthy controls.Patients with CIU showed significantly higher levels of anti-FcεRI antibody and anti-IgE antibody compared with patients with AU and healthy controls (all P ＜ 0.05).The serum IgE level in healthy controls was statistically lower than that in patients with AU (T =226.00,P ＜ 0.05),but higher than that in patients with CIU (T =190.00,P ＜ 0.05).ASST-positive patients with CIU had a higher level of serum anti-FcεRI antibody (T =101.73,P ＜ 0.05),but a similar level of serum anti-IgE antibody compared with ASST-negative patients with CIU (T =312.04,P ＞ 0.05).No significant differences were observed in the positivity rate of anti-HP antibody (29％,19％ and 23％,P ＞ 0.05) or TGAb (18％,15％ and 11％,P ＞ 0.05) between the patients with CIU,patients with AU and healthy controls.Both anti-HP antibody-positive patients and TGAb-positive patients with CIU showed a significantly higher positivity rate of anti-FcεRI antibody (all P ＜ 0.01),but a similar positivity rate of anti-IgE antibody compared with the patients with AU and healthy controls (all P ＞ 0.05).Conclusions Anti-FcεRI antibody and anti-IgE antibody are present in patients with CIU,and may play a certain role in the pathogenesis of CIU.

Detection of serum allergen specific IgE in the child with recurrent auergic purpura / 中国基层医药

Objective To investigate the role of allergen specific IgE in the child with recurrent auergic purpura,and to detect the relation between all kinds of allergen and the disease.Methods The serum specific IgE of allergen detected by ELISA in 100 cases of the child with recurrent auergic purpura.Results 81 cases of serum allergen-specific IgE were over than 50ku/L(81%).52 cases(52%)were positive reaction to more than two kinds of allergens and 29 cases(29%)were positive reaction to one kind of allergen.Several familiar aeroallergen mixed molds (19/100),dermatophagoides(12/100)and mugwort pollens(9/100).The most familiar food fish(28/100).shrimpand crab(22/100),milk(18/100).protein(11/100).Conclusion It suggests that aeroallergens,fish,shrimp and crab play an important role in the pathogenesis of repeating child anaphy lactic purpura.Mixed molds and protein foods are important pathogens to the disease.To detect the serum specific IgE could help screen allergens,and have important role to prevent disease.