Objectives This post-hoc analysis of CM310AD005 conductedaimed to analyze the efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis (AD) with and without prior systemic treatment.Methods In CM310AD005, eligible patients were randomized 1:1 to receive stapokibart 600 (loading dose)-300 mg and placebo Q2W for 16 weeks; all patients subsequently received stapokibart 300 mg Q2W for 36 weeks.Results At week 16, in systemic treatment-naïve patients, stapokibart led to significantly higher response rates than placebo for ≥75% improvement from baseline in the Eczema Area and Severity Index score (EASI-75, 70.3% vs. 29.1%), EASI-90 (38.1% vs. 13.3%), Investigator’s Global Assessment score of 0 or 1 (45.2% vs. 19.4%), and ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale score (34.8% vs. 13.9%) (all p < 0.0001). Among patients with prior systemic treatment, these response rates were also significantly higher in the stapokibart group, reaching 61.5% vs. 19.3%, 35.4% vs. 7.2%, 42.7% vs. 9.6%, and 37.5% vs. 7.2% (all p < 0.0001), respectively. All patients showed further improvements through week 52. The most common treatment-emergent adverse events were infections and infestations, occurring in 61.6% and 70.5% of patients with and without prior systemic treatment.Conclusions Stapokibart demonstrated significant clinical efficacy and manageable safety in AD patients irrespective of prior systemic treatment.

Objective:Vunakizumab is effective and safe for treating moderate-to-severe plaque psoriasis patients. This post hoc analysis was intended to assess the effects of vunakizumab in patients with different body mass index (BMI). Methods:In the phase III trial of vunakizumab (NCT04839016), 461 moderate-to-severe plaque psoriasis patients receiving vunakizumab were enrolled and categorized into baseline BMI<24 kg/m2 (N = 179), 24≤BMI<28 kg/m2 (N = 183), and BMI≥28 kg/m2 (N = 99) groups. At least 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75), PASI 90, PASI 100, static physician's global assessment (sPGA) 0/1, patient-reported outcomes (PROs), serum concentration of vunakizumab, and adverse events from week 0 (W0)-W52 were recorded. Results:A lower BMI was associated with higher W0--W12 accumulating PASI 75, PASI 90, PASI 100, and sPGA 0/1 response rates. From W0--W52, a lower BMI was associated with higher PASI 75, PASI 90, and PASI 100 scores at most time points and was related to sPGA 0/1 response rates from W4--W48. With respect to PROs, higher BMI was related to increased mean dermatology life quality index scores at several time points but was not associated with the mean worst itch numerical rating scale, EuroQoL-5D (EQ-5D) utility index, EQ-5D visual analog scale score, or short form-36 mental/physical component score. A lower BMI was related to a higher mean serum concentration of vunakizumab. The incidences of any adverse events and most specific adverse events did not differ among the groups. Conclusion:A lower BMI is associated with a greater treatment response and quality of life in moderate-to-severe plaque psoriasis patients receiving vunakizumab.

BACKGROUND:Eosinophils are involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE:This post-hoc analysis evaluated the effect of stapokibart on blood eosinophil counts in moderate-to-severe AD patients. METHODS:The phase II AD002 trial (n = 120) randomly assigned patients to stapokibart 300 mg every 2 weeks (Q2W), 150 mg Q2W, or placebo for 16 weeks. The phase III AD005 trial (n = 500) randomly assigned patients to stapokibart 300 mg Q2W or placebo for 16 weeks, followed by open-label stapokibart 300 mg Q2W for 36 weeks. Efficacy and safety were analyzed in subgroups stratified by baseline blood eosinophil counts (≥500 or <500 cells/µL). RESULTS:Stapokibart treatment resulted in sustained reductions in blood eosinophil counts versus placebo (baseline vs. Week 16: high-dose 420 vs. 235 cells/μL, low-dose 530 vs. 315 cells/μL in AD002; 370 vs. 210 cells/μL in AD005). Furthermore, stapokibart demonstrated superior efficacy over placebo in achieving higher Eczema Area and Severity Index (EASI)-75 response rates at Week 16 in both eosinophil subgroups. The incidence of adverse events was similar across eosinophil subgroups, with most events being mild or moderate. CONCLUSION:Stapokibart reduced blood eosinophil counts in AD patients and demonstrated favorable efficacy and safety regardless of baseline blood eosinophil counts.

The long-term efficacy of biologics in psoriasis is compromised by primary or secondary resistance, and poor treatment adherence due to frequent dosing. We assessed the efficacy and safety of switching to an interleukin-23 subunit p19 (IL23p19) inhibitor picankibart at 200 mg every 12 weeks, without a washout period, on skin clearance and quality of life (QoL) in patients with plaque psoriasis. A total of 152 patients were enrolled, comprising 83 suboptimal responders (static Physician’s Global Assessment [sPGA] ≥ 2 or body surface area [BSA] ≥ 3

BACKGROUND:Recent studies have shown that food allergen-specific IgE is associated with cardiovascular mortality. We aimed to investigate the associations of common food-specific IgE sensitization with all-cause, cancer, and non-cancer mortality. METHODS:This study was a cohort analysis using data from the 2005-2006 US National Health and Nutrition Examination Survey (NHANES). Participants examined for allergen-specific IgE were included, and mortality outcomes up to 2019 were ascertained through linkage with the National Death Index. Cox proportional hazards models adjusted for demographic, lifestyle, and clinical factors assessed associations between food-specific IgE sensitization and mortality, with subgroup analyses among participants consuming the corresponding foods. RESULTS:4,424 adults were included. During a median follow-up of 13.8 years, there were 879 (19.9%) all-cause mortality, including 705 non-cancer mortality and 174 cancer-related mortality. Sensitization to at least 1 animal-derived food (HR 1.32, 95% CI 1.02-1.70, p=0.035) was associated with higher all-cause mortality, particularly for sensitization to milk (HR 1.44, 95% CI 1.08-1.94, p=0.015), shrimp (HR 1.46, 95% CI 1.06-2.01, p=0.022), and egg (HR 1.30, 95% CI 1.04-1.63, p=0.023), but not peanut. For non-cancer mortality, consistent and stronger associations were observed. In food consumers, associations were further strengthened for sensitization to milk (HR 1.63, 95% CI 1.27-2.09, p<0.001), egg (HR 1.58, 95% CI 1.25-2.01, p<0.001), and shrimp (HR 1.89, 95% CI 1.02-3.50, p=0.043) as risk factors for non-cancer mortality. CONCLUSIONS:Food-specific IgE sensitization was associated with increased risks of all-cause and non-cancer mortality, suggesting that IgE sensitization may carry systemic implications extending beyond allergy.

Erythroderma is most often secondary to psoriasis, atopic dermatitis (AD), or drug eruption. These three subtypes have different immune mechanisms, but most biomarker studies treat erythroderma as one condition. We examined whether routine complete blood count (CBC) indices behave differently across the three subtypes. This was a single-center retrospective study of inpatients admitted between April 2015 and March 2026. We compared eosinophil-to-lymphocyte ratio (ELR), absolute eosinophil count (AEC), and neutrophil-to-lymphocyte ratio (NLR) between erythroderma cases and non-erythrodermic controls within each subtype, with Benjamini-Hochberg correction. We assessed ROC discrimination using a 5 000-iteration bootstrap and Harrell's optimism correction. Of 375 inpatients (18, 19, and 19 erythroderma cases in psoriasis-type, AD-type, and drug eruption-type), ELR was higher in cases than controls in all three subtypes (all q ≤ 0.007), with corrected AUCs of 0.84, 0.69, and 0.80. NLR was higher in cases for psoriasis-type (AUC 0.71) and AD-type (AUC 0.75) but not for drug eruption-type (AUC 0.56). In AD-type, a combined model with ELR and NLR gave a corrected AUC of 0.76; no gain was seen in the other two subtypes. In this small exploratory cohort, ELR appears higher in erythroderma across the three subtypes, while NLR carries information only in psoriasis-type and AD-type. The pattern is consistent with eosinophil-compartment activity being a shared feature and neutrophil-compartment activity being subtype-restricted. The findings are hypothesis-generating and need confirmation in prospective multicenter cohorts that can also control for pre-admission medication.

BACKGROUND:Effective topical therapies for mild-to-moderate atopic dermatitis (AD) should provide rapid itch relief, sustained anti-inflammatory efficacy and minimal local toxicity. Existing options, including corticosteroids and calcineurin inhibitors, are limited by long-term adverse effects, highlighting the need for safer, steroid-sparing alternatives. OBJECTIVES:To evaluate the efficacy and safety of ivarmacitinib ointment, a highly selective topical Janus kinase 1 inhibitor, applied twice daily in adults with mild-to-moderate AD. METHODS:This phase III evaluation was part of a multicentre randomized double-blind vehicle-controlled seamless adaptive phase II/III trial conducted at 27 sites in China. Adults aged 18-75 years with Hanifin-Rajka-defined mild-to-moderate AD were randomized (1 : 1 : 1) to ivarmacitinib ointment 0.5%, ivarmacitinib ointment 1% or vehicle for 8 weeks. Patients who initially received the vehicle were re-randomized to active treatment for a blinded extension through week 52. Co-primary endpoints were Investigator's Global Assessment (IGA) response (score 0/1 with ≥ 2-grade improvement) and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 8. RESULTS:At week 8, significantly more patients achieved an IGA response with ivarmacitinib than with vehicle [ivarmacitinib 0.5%: 21.3% vs. 10.6% (P = 0.02); ivarmacitinib 1%: 26.2% vs. 10.6% (P = 0.001)]. Likewise, EASI 75 responses were higher [ivarmacitinib 0.5%: 42.6% vs. 17.9%; ivarmacitinib 1%: 45.1% vs. 17.9% (both P < 0.001)]. Relief from pruritus was seen within 48 h and maintained through week 52, with sustained improvements in SCORing Atopic Dermatitis (SCORAD), affected body surface area and Dermatology Life Quality Index. During the vehicle-controlled period, treatment-emergent adverse events occurred in 42.6% (n = 52/122), 56.6% (n = 69/122) and 52.0% (n = 64/123) of patients in the ivarmacitinib 0.5%, ivarmacitinib 1% and vehicle groups, respectively; most were mild and infection-related events were infrequent. No treatment-related adverse event occurred in ≥ 2% of patients in the ivarmacitinib 1% or vehicle groups, while in the ivarmacitinib 0.5% group, only folliculitis (n = 5/122; 4.1%) and increased blood uric acid (n = 4/122; 3.3%) were reported in ≥ 2% of patients. No skin atrophy, telangiectasia or application-site irritation was observed. Long-term safety through week 52 remained consistent, with no new safety signals noted. CONCLUSIONS:Twice-daily ivarmacitinib ointment (0.5% or 1%) produced rapid, durable and well-tolerated improvements in the signs, symptoms and itch experienced by adults with mild-to-moderate AD, supporting its potential as a safe, steroid-sparing topical therapy.

SSGJ-608 is a recombinant, humanized, immunoglobulin G1 monoclonal antibody that targets human interleukin-17A with high specificity and high affinity. We aimed to evaluate the efficacy and safety of SSGJ-608 in patients with moderate-to-severe psoriasis in China. Adult patients aged 18 years or older with moderate-to-severe plaque psoriasis were randomly assigned (2:2:1) to receive subcutaneous injections of placebo (placebo group), 80 mg of SSGJ-608 every 2 weeks after a starting dose of 160 mg at week 0 (608A group), or 160 mg of SSGJ-608 every 4 weeks (608B group). At week 12, patients in the 608A group received SSGJ-608 80 mg every 4 weeks, patients in the 608B group received SSGJ-608 160 mg every 8 weeks, and patients in the placebo group were re-allocated (1:1) to either the 608A or 608B group to receive 608 80 mg every 4 weeks (with an additional 160-mg loading dose of SSGJ-608 at week 12) or 160 mg every 8 weeks. All patients received treatment until week 48. The primary endpoints were a ≥75

BACKGROUND:Generalized pustular psoriasis (GPP) is a rare, severe inflammatory skin disease characterized by acute flares. Recibokibart is a humanized IgG1 monoclonal antibody targeting the interleukin-36 (IL-36) receptor. In a phase 1b open-label study, a single intravenous dose of recibokibart was associated with an acceptable safety profile and rapid improvements in pustulation, overall skin disease severity, and systemic inflammatory markers through 12 weeks. OBJECTIVES:This study aimed to evaluate the efficacy and safety of recibokibart in patients with acute flares of GPP. METHODS:In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial conducted in China, patients with moderate-to-severe acute GPP were randomly assigned in a 2:1 ratio to receive a single intravenous dose of recibokibart (1050 mg) or placebo at day 1. Patients with persistent disease activity at day 8 were eligible to receive open-label recibokibart, and patients with recurrent flares after achieving a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 0 or 1 could receive an additional open-label dose. The primary efficacy endpoint was the proportion of patients who achieved a GPPGA pustulation sub-score of 0 or 1 at week 1 (day 8). RESULTS:A total of 33 patients were randomized (recibokibart, n=22; placebo, n=11). At week 1 (day 8), the primary endpoint of achieving a GPPGA pustulation sub-score of 0 or 1 was met by 86.4% of patients in the recibokibart group versus 9.1% in the placebo group (between-group difference, 77.3%; 95% CI, 42.5-88.9; P<0.0001). At week 1 (day 8), greater improvements were observed with recibokibart across key secondary endpoints, including achievement of a GPPGA total score of 0 or 1 (63.6% vs. 0%), complete pustule clearance (54.5% vs. 0%), and mean percentage change from baseline in GPPASI (-59.3% vs. 0%). By week 4, 72.7% of patients treated with recibokibart achieved GPPASI 75. Clinical improvements were observed as early as 24 hours after treatment and were maintained through week 12, although assessments after day 8 included patients who received open-label treatment. The most frequently reported adverse events with recibokibart included hypoproteinemia, hypertriglyceridemia, hyperlipidemia, and pruritus. CONCLUSIONS:A single intravenous dose of recibokibart resulted in rapid improvement in pustular and overall skin disease severity in patients with acute GPP flares, with an acceptable safety profile.

ICP-332 is a tyrosine kinase 2 inhibitor currently under investigation for the treatment of atopic dermatitis (AD). To evaluate the safety and efficacy of ICP-332 for moderate to severe AD. This double-blind, placebo-controlled, phase 2 randomized clinical trial was conducted between February 6 and November 7, 2023, across 19 centers in China. Individuals aged 18 to 75 years who had diagnosis of AD for 1 year or longer and a history of contraindication or inadequate response to topical therapies were included. Participants were randomized 1:1:1 to receive ICP-332 at 80 mg or 120 mg, or placebo orally once daily for 4 weeks. Study participants and personnel were blinded to group assignment. The primary outcome was safety. The key efficacy outcome was the percentage change from baseline in Eczema Area and Severity Index (EASI) at week 4. Other outcomes included percentages of patients achieving EASI-75 (a ≥75% improvement in EASI) and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or more points improvement. This study included 75 patients (mean [SD] age, 37.3 [18.0] years in the ICP-332 groups and 44.5 [17.4] years in the placebo group; 21 women [28%] and 54 men [72%]). Among the 74 patients included in the safety set, 17 of 25 (68%) in the placebo group, 19 of 25 (76%) in the 80-mg ICP-332 group, and 18 of 24 (75%) in the 120-mg ICP-332 group experienced treatment-emergent adverse events, with all events being mild or moderate. The most common adverse event was decreased blood fibrinogen (1 of 25 [4%] in the placebo group, 6 of 25 [44%] in the 80-mg ICP-332 group, and 5 of 24 [21%] in the 120-mg ICP-332 group). Percentage reductions in EASI at week 4 were −78.2% (95% CI, −89.8% to −66.6%) in the 80-mg ICP-332 group, −72.5% (95% CI, −84.3% to −60.7%) in the 120-mg ICP-332 group, and −16.7% (95% CI, −28.7% to −4.6%) for those receiving placebo. Mean differences vs placebo for percentage reductions from baseline at week 4 in EASI were −61.6% (95% CI, −78.4% to −44.7%; P < .001) and −55.8% (95% CI, −72.8% to −38.9%; P < .001) for 80-mg ICP-332 and 120-mg ICP-332, respectively. There was a statistically significant higher EASI-75 response rate with both ICP-332 doses (64.0% for each; difference vs placebo, 56.0%; 95% CI, 34.4%-77.6%; P < .001) than with placebo and a greater percentage of Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and improvement of 2 or more points at week 4 in the 80-mg ICP-332 group vs placebo (36.0%; difference vs placebo, 32.0%; 95% CI, 11.7%-52.3%; P = .005). In this phase 2 randomized clinical trial, ICP-332 demonstrated a favorable safety profile and encouraging efficacy, supporting further development for AD. ClinicalTrials.gov Identifier: NCT05702268

BACKGROUND:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous adverse drug reactions still with controversy in treatment. Complete blood cell count-derived inflammatory biomarkers reflect systemic inflammation, and their value in SJS/TEN has not been fully studied. OBJECTIVES:To compare the therapeutic efficacy of corticosteroid combined with adalimumab (CA), corticosteroid combined with intravenous immunoglobulin (CI) and corticosteroid monotherapy (CM), and explore prognosticators on severity and prognosis of SJS/TEN. METHODS:All inpatients with SJS/TEN treated with CA, CI or CM in two hospitals between 2015 and 2024 were studied. We calculated biomarkers, including the neutrophil/lymphocyte ratio (NLR), derived neutrophil/(leucocyte minus neutrophil) ratio (dNLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and neutrophil/(lymphocyte × platelet) ratio (NLPR), and analysed their correlations with severity and prognosis. RESULTS:Among 136 patients, 29 patients were treated with CA, 18 patients were treated with CI and 89 patients were treated with CM. The mortality rate in the three groups was much lower than expected based on the Severity of Illness Score for Toxic Epidermal Necrolysis (SCORTEN). The days to improvement of original lesions and days to no new lesions developing in CA and CI were significantly fewer than those in CM. NLR, dNLR, PLR and NLPR were independent risk factors for the elevation of the SCORTEN score, and MLR was an independent prognostic factor for healing time. CONCLUSIONS:The therapeutic efficacy of CA and CI is better than CM, and the incidence of complications is not increased. NLR, dNLR, PLR and NLPR may serve as potential prognosticators of severity in SJS/TEN. Higher MLR appears to be a potential poor prognostic factor for healing.

BackgroundPsoriasis is an immune-mediated skin disease, of which plaque psoriasis is the predominant form. This study aimed to understand the clinical characteristics of patients with moderate-to-severe plaque psoriasis who received systemic medications in a real-world setting in China.MethodsIn this retrospective observational study, patients with moderate-to-severe plaque psoriasis were identified in electronic medical record databases from two study centers in China between January 1, 2018, and December 31, 2021. Analyses were conducted on patients with a follow-up period of >= 6 months. Primary objectives were to describe demographics, clinical characteristics, treatment experiences, and patterns of systemic treatments among this population. Secondary objectives were to describe healthcare resource utilization.ResultsAmong 1102 eligible patients included in the systemic treatment analysis set, the mean (standard deviation [SD]) age was 44.9 (14.6) years, and 77% of patients were male. The most common comorbidity was allergic disease and skin disease (11%). Most patients received conventional systemic medications (84%), while few received biologic treatments (16%); 88% of patients discontinued systemic treatments within 90 days of the last prescription, 6% switched to a new systemic medication. The mean (SD) number of visits per patient-year was 6.5 (5.2) for outpatient and 0.9 (not applicable [NA]) for inpatient. The mean (SD) duration of inpatient visits per patient-year was 9.3 (NA) days, with a mean (SD) monthly direct medical cost of CYN 371.09 (741.56).ConclusionsThese results provide valuable insights for guiding decision-making for patients with plaque psoriasis. The high treatment discontinuation rate reflects a challenge to disease management and suggests better treatment options are needed for this patient population in China.

BACKGROUND:We conducted a phase IIb clinical trial of pumecitinib 3% gel (PG-011), a novel selective Janus kinase (JAK)1/2 inhibitor, applied topically to treat mild-to-moderate atopic dermatitis (AD). OBJECTIVES:To assess pumecitinib 3% gel for its efficacy and safety in treating adult patients with mild-to-moderate AD, and to determine the optimal treatment regimen. METHODS:In this study, 139 participants with mild-to-moderate AD were randomized 1 : 1 : 1 to pumecitinib 3% gel twice daily (n = 47), pumecitinib 3% gel once daily (n = 46) and placebo (n = 46) for 8 weeks of treatment. Percentage change in Eczema Area and Severity Index (EASI) score from baseline to week 8 was the primary efficacy endpoint. The percentage of participants with an Investigator's Global Assessment score of 0 or 1 (≥ 2-point improvement from baseline) at week 8, the proportion of participants attaining ≥ 50% improvement in EASI (EASI 50), ≥ 75% improvement in EASI (EASI 75) and ≥ 90% improvement in EASI (EASI 90) at week 8, and improvement in quality of life were also evaluated. Safety, local tolerability and some pharmacokinetics were monitored. RESULTS:At week 8, the percentage change from baseline in EASI score in the pumecitinib 3% gel twice daily, pumecitinib 3% gel once daily and placebo groups was -83.6%, -44.0% and -22.0%, respectively. Both pumecitinib treatment regimens showed a significantly greater effect compared with placebo (P < 0.006) and the pumecitinib 3% gel twice-daily regimen had a greater effect than once-daily treatment (P < 0.001). Other efficacy endpoints were also improved in participants in the pumecitinib groups vs. those in the placebo group, and pumecitinib 3% gel twice daily consistently exhibited better efficacy than the once-daily treatment. With regard to safety, the rate of adverse events in the pumecitinib and placebo groups was 48% and 48%, respectively. Safety profiles were generally similar between the pumecitinib and placebo groups, and treatment was well tolerated. Mean plasma drug concentrations were low (range 38-104 pg mL-1) over the 8-week treatment period. CONCLUSIONS:Pumecitinib 3% gel showed good efficacy and safety profiles in the treatment of adults with mild-to-moderate AD. The pumecitinib 3% twice-daily treatment regimen showed greater efficacy than the once-daily regimen in treating mild-to-moderate AD. Pumecitinib 3% gel was well tolerated and generated low systemic drug exposure when used topically. It may be a new choice of topical JAK inhibitor to treat mild-to-moderate AD.