Almirall (Spain)

This study aimed to evaluate the efficacy and safety of sarecycline in Chinese patients with moderate-to-severe acne vulgaris (AV). The 12-week (W) randomized, multicenter, double-blind (DB), placebo-controlled phase 3 trial was conducted from 29 October 2021 to 14 October 2022 at 34 centers in China, with a 36W open-label follow-up (OLFU) until 23 June 2023 for patients who responded to treatment during the DB period. Patients aged 9-45years with AV were randomized (2:1) to sarecycline (approximately 1.5mg/kg/day) or placebo for 12W. Treatment responders received sarecycline for an additional 12W if acne recurred during the OLFU. Endpoints were absolute change from baseline (CFB) and percent CFB (%CFB) to W3, W6, W9 and W12 in facial inflammatory lesion counts. Three hundred ninety-one patients comprised the intent-to-treat analysis set (mean age: 21.9years; 58.6% female). Sarecycline-treated patients had a statistically significantly greater reduction in the mean (standard error [SE]) absolute and %CFB to W12 in facial inflammatory lesion counts than placebo-treated patients: - 24.3 (0.7) vs. - 15.4 (1.0) (p < 0.001) and - 73.2% vs. - 46.0% (p < 0.001), respectively, with improvements observed as early as W3. Sarecycline was safe and well tolerated through W12. Incidence of treatment-emergent adverse events (TEAEs) with sarecycline (48.3%) was similar to that of placebo (49.6%). Most TEAEs were mild (87.3%), and few patients reported TEAEs that led to discontinuation of sarecycline (1.9%) or placebo (2.3%). Notably, patients whose acne recurred in the OLFU (23/45 [51.1%]) responded well to a second 12W course of sarecycline with a mean (standard deviation [SD]) reduction of - 23.1 (8.9) in the absolute CFB to the first visit after treatment reinitiation in facial inflammatory lesion counts. Sarecycline was effective and had an acceptable safety profile in treating moderate-to-severe AV in Chinese patients, supporting its value for treating AV in this population. Chinese Clinical Trial Registry (CTR20211314); http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml .

The efficacy and safety of lebrikizumab, a high-affinity monoclonal antibody targeting interleukin-13, were investigated in patients with moderate-to-severe atopic dermatitis (AD) up to 52weeks in phase3 trials. This analysis evaluates safety and maintenance of response through 104weeks of lebrikizumab treatment in patients with moderate-to-severe AD who achieved clinical response with lebrikizumab at week16. ADjoin is a 100-week phase3 long-term extension study. Adult and adolescent patients with moderate-to-severe AD were enrolled into parent studies ADvocate1, ADvocate2, and ADhere. ADvocate1&2 week16 lebrikizumab clinical responders (patients who achieved Investigator's Global Assessment [IGA] [0, 1] or Eczema Area and Severity Index [EASI]75 without rescue) were re-randomized 2:2:1 to lebrikizumab 250mgQ2W, Q4W, or placebo (lebrikizumab withdrawal). Patients who completed week52 of ADvocate1&2 could enroll into ADjoin. ADhere week16 lebrikizumab clinical responders could enroll into ADjoin and were randomized 2:1 to lebrikizumab 250mgQ2W or Q4W. Analyses were performed on patients who received 104weeks of lebrikizumab treatment in parent and extension studies combined. Efficacy analyses are reported as observed from week16 for patients who were re-randomized to lebrikizumab Q2W or Q4W. Safety assessments included monitoring adverse events. IGA(0, 1) was maintained by 86.4% (Q2W) and 76.4% (Q4W) patients from ADvocate1&2 and 83.9% (Q2W) and 78.6% (Q4W) patients from ADhere at week104. EASI75 was maintained by 95.6% (Q2W) and 96.3% (Q4W) ADvocate1&2 patients and 95.1% (Q2W) and 96.0% (Q4W) ADhere patients at week104. Pruritus NRS ≥ 4-point improvement was maintained by 100% (Q2W) and 89.7% (Q4W) ADvocate1&2 patients at week104 and 81.8% (Q2W) and 90.0% (Q4W) ADhere patients at week68. During ADjoin, adverse events were reported by 62.2% of patients from ADvocate1&2 and ADhere who received lebrikizumab Q2W or Q4W, with the majority being mild (31.5%) or moderate (27.0%) in severity, and 2.2% leading to discontinuation due to adverse event. Skin and itch outcomes were maintained over 2years of continuous lebrikizumab 250mg treatment. The safety profile of lebrikizumab in ADjoin is consistent with previous lebrikizumab studies in patients with moderate-to-severe AD. ClinicalTrials.gov, NCT04392154.

IntroductionA systematic literature review and network meta-analysis (NMA) were conducted to compare the short-term efficacy of lebrikizumab to other biologic and Janus kinase (JAK) inhibitor monotherapies approved for moderate-to-severe atopic dermatitis in adults and adolescents.MethodsThe NMA included randomized, double-blind, placebo-controlled monotherapy phase 2 and 3 trials of biologics (lebrikizumab 250 mg every 2 weeks [Q2W], dupilumab 300 mg Q2W, and tralokinumab 300 mg Q2W) and JAK inhibitors (abrocitinib 100/200 mg daily, baricitinib 2/4 mg daily, and upadacitinib 15/30 mg daily) at approved doses. Efficacy outcomes included the proportions of patients achieving Eczema Area and Severity Index (EASI) improvement, an Investigator Global Assessment of 0 or 1 (IGA 0/1), and a ≥ 4-point improvement in pruritus/itch numeric rating scale score at 12 weeks (abrocitinib) or 16 weeks (other treatments). Itch was also assessed at week 4. A Bayesian NMA employing baseline risk-adjusted random effects models was used to estimate treatment differences.ResultsTwenty-two monotherapy studies involving 8531 patients were included in the NMA. By week 12/16, lebrikizumab had superior odds of achieving IGA 0/1 and itch improvement compared to baricitinib and tralokinumab; similar odds to dupilumab, abrocitinib, and upadacitinib 15 mg; and inferior odds to upadacitinib 30 mg. Additionally, lebrikizumab had a higher probability of improving EASI than baricitinib 2 mg; similar probability to baricitinib 4 mg, tralokinumab, dupilumab, abrocitinib, and upadacitinib 15 mg; and lower probability than upadacitinib 30 mg daily. At week 4, lebrikizumab had superior odds of improving itch compared to tralokinumab; similar odds to baricitinib, dupilumab, and abrocitinib 100 mg; and inferior odds to abrocitinib 200 mg and upadacitinib.ConclusionAmong biologics, lebrikizumab was comparable to dupilumab and superior to tralokinumab in improving response rates at week 16. Upadacitinib 30 mg was the only JAK inhibitor with superior response rates compared to lebrikizumab.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-025-01357-7.

The current management of psoriasis does not differentiate between younger and older patients in selecting the safest and/or most effective biologic. To explore the effect of age at treatment initiation in response to biologics in patients with moderate-to-severe psoriasis in the UK and Eire. Data from patients registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2024 on a first course of tumour necrosis factor (TNF), interleukin (IL)-12/IL-23, IL-17 and IL-23 inhibitors with at least 6 months' follow-up were included. Patients aged ≥ 16 years at registration were organized into the following cohorts: 16-24 years, 25-34 years, 35-44 years, 45-54 years, 55-64 years, 65-74 years and ≥ 75 years. The 45-54 years age group was used as the reference cohort. Biologic survival was defined as the time between treatment initiation to its discontinuation associated with ineffectiveness or the occurrence of adverse events (AEs). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) was estimated using a flexible parametric model to compare discontinuing treatment between the age groups. Each model included exposure (biologic class), effect modifier (age groups), interaction terms, baseline demographics and clinical and disease severity covariates. In total, 14 294 patients were included and organized into the following age groups: 16-24 years, n = 847 (5.9%); 25-34 years, n = 2502 (17.5%); 35-44 years, n = 3575 (25.0%); 45-54 years, n = 3863 (27.0%); 55-64 years, n = 2338 (16.4%); 65-74 years, n = 954 (6.8%); and ≥ 75 years, n = 215 (1.5%). The interaction effects model showed that individuals aged 16-24 years were more likely to discontinue TNF inhibitors (TNFi) due to ineffectiveness than those in the reference cohort (aHR 1.30, 95% CI 1.10-1.55). For survival associated with AEs, individuals aged 55-64 years were at higher risk of discontinuing TNFi and IL-12/IL-23 inhibitors [IL-12i/IL-23i; aHR 1.33 (95% CI 1.13-1.56) and aHR 1.34 (95% CI 1.03-1.75), respectively]; those aged 65-74 years were more likely to discontinue TNFi, IL-12i/IL-23i and IL-17 inhibitors [aHR 1.89 (95% CI 1.54-2.31), aHR 2.00 (95% CI 1.47-2.73) and aHR 1.69 (95% CI 1.08-2.64), respectively], whereas individuals aged ≥ 75 years were at higher risk of discontinuing the four biologic classes. Patients aged 16-24 years with psoriasis are more likely to stop TNFi due to ineffectiveness, whereas those aged ≥ 55 years are more likely to stop biologics due to AEs. These real-world findings provide important information for clinicians treating people with moderate-to-severe psoriasis across all age groups.

Chronic plaque psoriasis negatively impacts patients’ work productivity, with potential substantial financial implications. This post hoc analysis assessed associations between disease (itch, pain, dermatology life quality index [DLQI], and psoriasis area and severity index [PASI])‐ and work‐related outcome measures (absenteeism, presenteeism, and activity and work impairment) in 116 patients with moderate‐to‐severe plaque psoriasis treated with tildrakizumab for 24 weeks. We extrapolated the potential economic value of reducing work productivity loss with tildrakizumab treatment in society, using Norway as a model. Elevated pain and DLQI scores significantly increased the degree of absenteeism, and pain, DLQI, and itch were significantly positively associated with presenteeism, activity impairment, and work impairment. The PASI did not associate with any work outcome measure. Economic impact due to work productivity loss was extrapolated at approximately EUR 12,700 per person annually. In conclusion, all disease outcome measures except the PASI were associated with a work‐related outcome measure, indicating that more holistic measures for assessing psoriasis disease burden may be more beneficial from a patient perspective. Additionally, the economic value of reduced work productivity loss due to tildrakizumab treatment was extrapolated to be substantial in Norwegian society, suggesting that managing plaque psoriasis with this biologic could be clinically and economically beneficial.

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Abstract Introduction Historically, atopic dermatitis (AD) was believed to affect primarily children. However, a recent meta-analysis of 17 studies reporting age of AD onset as &amp;gt;16 years found that the pooled proportion of adult-onset AD was 26.1%, and that AD onset can occur at all ages. Lebrikizumab (LEB) is a high-affinity monoclonal antibody which targets IL-13, the key cytokine implicated in AD. Objectives This analysis investigated the efficacy and safety of lebrikizumab in adults ≥60 years with moderate-to-severe AD. Methods Data for patients aged ≥60 years from two Phase 3 trials, ADvocate1 and ADvocate2, were pooled. A total of 98 patients ≥ 60 years participated in the ADvocate trials (N=28 placebo (PBO), N=70 LEB). Patients were treated with lebrikizumab 250mg every 2 weeks or PBO, for 16 Weeks. Baseline demographics and characteristics were recorded. Efficacy was assessed in the pooled modified intent to treat population at Week 16 with Investigator’s Global Assessment (IGA) (0,1) with ≥2-point improvement, ≥75% improvement in Eczema Area and Severity Index (EASI 75), EASI percentage change from baseline (CFB), and Pruritus Numeric Rating Scale (NRS) ≥4-point improvement. Categorical outcomes were evaluated by Cochran Mantel Haenszel tests to compare treatment groups. Continuous outcomes were analyzed using the analysis of covariance model. Data collected after use of rescue medication or discontinuation due to lack of efficacy were imputed with non-responder imputation (NRI) for categorical endpoints, or baseline values for continuous endpoints. Data collected after discontinuation for other reasons were set to missing and missing data were imputed with multiple imputation. Safety was also assessed in the integrated modified safety population. Results The baseline mean age was 67.2 years (standard deviation [SD] 6.7, range 60-93) in LEB- treated patients and 69 years ([6.2], range 60-85) in PBO. The LEB-treated population was 62.9% male (n=44/70) vs PBO 46.4% (n=13/28). Race was comparable between groups. At baseline 67.1% LEB (n=47/70) and 57.1% PBO (n=16/28) patients had IGA 3, while 32.9% LEB (n=23/70) and 42.9% PBO (n=12/28) had IGA 4. Other baseline characteristics were comparable: EASI: LEB 26.1, [10.6] vs PBO 27.1, [8.1]; BSA: LEB 38.3, [19.8] vs. PBO 40.9, [18.1]; and Pruritus NRS: LEB 7.5, [2.0] vs PBO 7.4, [1.7]. At Week 16, IGA (0,1) was achieved by 34.5% LEB-treated patients vs 11% PBO (P=0.022). EASI 75 was achieved by 48.9% and 16.3% of LEB- and PBO-treated patients, respectively (P=0.004). Pruritus NRS with ≥4-point improvement was reported by 45.5% and 12.2% of LEB vs PBO, respectively (P=0.004). The mean percent CFB EASI was LEB -58.5% (SE 8.5) and PBO -29.4% (SE 11.1) (P=0.002). Safety results in the older adult population were consistent with the overall modified safety population. Conclusions At Week 16, efficacy and patient reported outcome endpoints were met in the older adult population. These results indicate that lebrikizumab is an effective treatment for moderate-to-severe AD in the adult population ≥60 years of age and has a consistent safety profile.

The combined treatment with calcipotriol (Cal) and betamethasone dipropionate (BDP) has emerged as the leading anti-psoriatic topical treatment. Fixed-dose Cal/BDP is available in different formulations, including ointment, gel, foam, and cream. This review examines the mechanism of action of Cal/BDP underlying its therapeutic effect and compiles the evidence regarding its efficacy and safety compared to monotherapy with topical corticosteroids. The dual-action of Cal/BDP targets the inflammatory pathways and abnormal keratinocyte proliferation, both of them fundamental mechanisms of psoriasis pathogenesis. A large number of randomized, double-blind studies support Cal/BDP superiority over topical corticosteroids, demonstrating its broad efficacy across several degrees of psoriasis severity and its capability to provide early significant clinical improvements. This increased efficacy is achieved without negative effects on the safety profile, since the incidence of adverse effects reported with Cal/BDP is usually similar to that of BDP and even lower than that of Cal alone. The combination therapy rapid onset of action, coupled with a simplified dosing regimen, has been identified as crucial for improving long-term adherence and patient outcomes. In conclusion, Cal/BDP is confirmed as a versatile, effective, and convenient option for the patient in psoriasis management.