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Background The anti-interleukin-23 antibody guselkumab (GUS) demonstrated favourable week 24 efficacy and safety over fumaric acid esters (FAE) in systemic treatment-naïve patients with moderate-to-severe plaque psoriasis (study part I). Objectives To compare, in study part II, the sustainability of treatment responses (weeks 24–32) in GUS- and FAE-treated patients and treatment responses (weeks 32–56) in patients treated with GUS and FAE and in FAE nonresponders switching to GUS; and, in part III, to investigate the maintenance of response through week 100 in patients withdrawn from GUS at week 56. Methods At week 0, systemic treatment-naïve patients were randomized 1 : 1 to GUS or FAE as per label. At week 32, patients with a Psoriasis Area and Severity Index (PASI) 75 (≥ 75% improvement in PASI score) response (r) continued assigned treatment (GUSr-GUS; FAEr-FAE), whereas nonresponders (nr) received GUS (FAEnr-GUS; GUSnr-GUS). GUS-treated patients with a week 56 PASI 90 response (≥ 90% improvement in PASI score) were withdrawn (w) and followed until loss of response or week 100. Results At week 32, 98% (n = 54/55) of GUS- and 41% (n = 14/34) of FAE-treated patients were PASI 75 responders. At week 56, 91%, 50% and 80% of GUSr-GUS, FAEr-FAE and FAEnr-GUS patients, respectively, achieved a PASI 90 response; 72%, 29% and 45%, respectively, achieved a Dermatology Life Quality Index score of 0/1. At week 100, 44 weeks postwithdrawal, 47% (n = 17/36) and 25% (n = 3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained a PASI score ≤ 5. Overall, the adverse event and discontinuation rates were lower for GUS than FAE. Conclusions In these exploratory analyses, GUS, as a first-line systemic treatment or second-line systemic treatment in FAE nonresponders, was associated with long-term clinical efficacy up to week 100, including a withdrawal period. [ABSTRACT FROM AUTHOR]

Background Patients with psoriasis require long-term management; therefore, understanding the long-term safety of new treatments, such as bimekizumab (BKZ), is crucial. Objectives To evaluate BKZ's 3-year safety profile in patients with moderate-to-severe plaque psoriasis. Methods Three years of safety data were pooled from three phase III trials (BE VIVID, BE READY and BE SURE) and their ongoing open-label extension (BE BRIGHT). Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). Results In total, 1495 patients received at least one BKZ dose; total BKZ exposure was 3876.4 PY. The overall EAIR of TEAEs was 175.5/100 PY and decreased with longer exposure to BKZ. The most commonly reported TEAEs were nasopharyngitis, oral candidiasis and upper respiratory tract infection (EAIRs of 15.0/100 PY, 10.1/100 PY and 6.5/100 PY, respectively); 99.3% of oral candidiasis events were mild or moderate in severity, none were serious and few led to discontinuation. EAIRs of other TEAEs of interest were low, including serious infections (1.2/100 PY), adjudicated inflammatory bowel disease (0.2/100 PY) and laboratory elevations in aspartate aminotransferase or alanine aminotransferase (> 5 × upper limit of normal: 0.6/100 PY). Conclusions In these analyses pooled across 3 years, no new safety signals were observed with longer exposure to BKZ. The vast majority of oral candidiasis events were mild or moderate in severity, as reported previously. [ABSTRACT FROM AUTHOR]

Introduction/Background In the DELTA-2 (NCT04872101) Phase 3 trial, delgocitinib cream 20 mg/g, a topical pan-Janus kinase inhibitor, was well-tolerated and demonstrated significant improvement in all efficacy endpoints versus cream vehicle in adults with moderate to severe chronic hand eczema (CHE). Objectives The objectives of this analysis were (1) to examine systemic exposure of delgocitinib cream 20 mg/g in adults with moderate to severe CHE in the randomized, double-blind, vehicle-controlled DELTA-2 trial (2) to compare the DELTA-2 systemic exposure with corresponding data following oral administration of delgocitinib in a Phase 1 trial, (3) to present a summary of safety related to delgocitinib cream from the randomized, double-blind, vehicle-controlled DELTA-2 trial. Methods Pharmacokinetic blood sampling in DELTA-2 was performed 2-6 hours after delgocitinib application at Weeks 1, 4, and 16 using a liquid chromatography/mass spectrometry-based method (lower limit of quantitation: 5 pg/ml). In the Phase 1 trial (NCT05050279), single oral doses of delgocitinib were tested in healthy volunteers with sampling performed for up to 24-hours post-administration. Results In DELTA-2, minimal systemic exposure was recorded in 313 delgocitinib-treated patients, with the highest geometric mean plasma concentration being 0.21 ng/ml at Week 1 (n=286). In the Phase 1 trial, the lowest oral delgocitinib dose tested (1.5 mg; n=8) is regarded as subtherapeutic and showed a peak systemic exposure (geometric mean Cmax) of 7.2 ng/ml. In DELTA-2, adverse events (AEs) were reported by 45.7% (n=143/313; delgocitinib cream) and 44.7% (n=71/159; cream vehicle) of patients, with COVID-19 being most common (11.5% vs 12.6%, respectively). The rate of possibly or probably related AEs was low and similar between delgocitinib cream and cream vehicle. No deaths were reported. Few serious AEs were reported with none assessed as related to the study drug. Conclusions The DELTA-2 trial demonstrated minimal systemic exposure in association with a favorable safety profile, supporting a lack of meaningful systemic effect from twice-daily applications of delgocitinib cream in patients with moderate to severe CHE. [ABSTRACT FROM AUTHOR]

Background Itch is the most burdensome symptom of atopic dermatitis (AD) that severely affects sleep and overall and quality of life.1,2 Rapid control of itch could be instrumental in minimizing disease symptoms and the associated burden for patients.3,4 Nemolizumab, an interleukin-31 (IL-31) alpha antagonist, inhibits the IL-31 pathway of itch and inflammation in AD.5 Objectives To evaluate speed of onset of itch relief and sleep improvements with nemolizumab in moderate-to-severe AD. Methods ARCADIA-1 and ARCADIA-2 were two identical, randomized, double-blinded, placebo-controlled studies. Patients (≥12 years) with moderate-to-severe AD and inadequate response to topical corticosteroids (TCS) were randomized (2:1) to receive nemolizumab 30mg every 4 weeks (60mg baseline loading dose) or matching placebo, both with background TCS of low/medium potency with/without topical calcineurin inhibitors (TCI). Results Significant improvements in itch (least squares [LS] mean±standard error [SE] change from baseline [CFB] in Peak Pruritus Numeric Rating Scale [PP-NRS]) were noted in nemolizumab-treated vs placebo-treated patients by Day 1 in ARCADIA-1 (-0.9±0.08 vs -0.4±0.10) and ARCADIA-2 (-1.1±0.09 vs -0.4±0.12), reaching -2.4±0.08 vs -1.2±0.11 and -2.3 ±0.09 vs -0.9±0.12 respectively at Day 14 (p <0.001 for all). Significantly greater proportions of nemolizumab-treated vs placebo-treated patients achieved ≥4-point improvement in PP-NRS by Day 2 in ARCADIA-1 (9.4% vs 3.4%, p<0.01) and Day 1 in ARCADIA-2 (8.2% vs 1.9%, p<0.001) and through Day 14 (ARCADIA-1: 22.7% vs 10.6%, p<0.0001; ARCADIA-2: 23.4% vs 6.8%, p <0.0001). Conclusions Treatment with nemolizumab plus TCS/TCI resulted in rapid, statistically and clinically significant improvements in itch in moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction/Background Patients with atopic dermatitis (AD) have an increased risk of cutaneous, extracutaneous, and systemic infections with a considerable associated cost burden. Certain treatments used to manage AD, such as immunosuppressants and Janus kinase inhibitors, can increase the risk of infection. Data from the LIBERTY AD open-label extension study (OLE; NCT01949311) indicate that continuous dupilumab treatment for up to 4 years in adults with moderate-to-severe AD is not associated with an increased risk of overall systemic or cutaneous infections.1 Objectives To report exposure-adjusted incidence rates (EAIR) of infections in adults with moderate-to-severe AD treated with dupilumab for up to 5 years. Methods The OLE was a phase 3, multicenter, open-label extension trial that enrolled adults with moderate-to-severe AD who had participated in any dupilumab parent study (phase 1–3). During the OLE, patients were treated with 300mg dupilumab weekly (qw). 226 patients transitioned to 300mg every 2 weeks starting from Week 108 to align with approved dosage. Concomitant topical treatments for AD were permitted. The EAIR (patients with ≥1 event/100 patient-years [nP/100PY]) was calculated for treatment-emergent infections (Medical Dictionary for Regulatory Activities [MedDRA] System Organ Class [SOC] infections and infestations) and skin infections for the overall study population (N=2,677). Skin infections were defined as adjudicated non-herpetic skin infections from the SOC infections and infestations plus, conservatively, all MedDRA Preferred Terms (PT) in MedDRA High Level Term herpes viral infections. Because the OLE lacked a control arm, infection data from adults with moderate-to-severe AD receiving placebo qw + topical corticosteroids (TCS) in the 1-year LIBERTY AD CHRONOS trial (NCT02260986; n=315) are included for comparison. Data are presented as observed. Results From the 2,677 patients enrolled, 2,207/557/334 completed treatment up to Week 52/148/260. The most common reasons for study withdrawal during the OLE were dupilumab approval and commercialization (810/1,380 patients; 58.7% of withdrawals) and patient withdrawal (248/1,380 [18.0%]). Treatment-emergent adverse events led to permanent discontinuation in 101 (3.8%) patients. The EAIR of patients with ≥1 treatment-emergent infection was lower in this OLE vs the placebo qw + TCS arm of the 1-year CHRONOS trial (70.7 vs 107.0 nP/100PY). Over this 5-year OLE, 50 patients (0.9 nP/100PY) had ≥1 serious infection, 53 (0.9 nP/100PY) had ≥1 severe infection, and 20 (0.3 nP/100PY) experienced ≥1 infection resulting in permanent treatment discontinuation. Skin infections were reported in 535 patients (11.0 nP/100PY), comprising non-herpetic skin infections (249 patients; 4.6 nP/100 PY) and herpes viral infections (343 patients; 6.6 nP/100 PY). The EAIR of skin infections decreased throughout the OLE (1 year: 17.2 nP/100 PY; 3 years: 11.9 nP/100 PY; 5 years: 11.0 nP/100 PY) and was lower than the CHRONOS placebo qw + TCS arm (29.5 nP/100 PY). The most common PTs (≥5.0 nP/100PY) from the SOC infections and infestations were nasopharyngitis (774 patients; 17.6 nP/100PY), upper respiratory tract infection (365 patients; 7.0 nP/100PY), and conjunctivitis (277 patients; 5.2 nP/100PY; representing conjunctivitis of unspecified or undetermined etiology, including non-infectious cases). Conjunctivitis was the most common infection PT leading to treatment discontinuation (10 patients; 0.2 nP/100PY). The EAIR of serious infections remained stable during the OLE (1 year: 0.8 nP/100PY; 3 years: 0.9 nP/100PY; 5 years: 0.9 nP/100PY). Conclusions Long-term dupilumab treatment in adults with moderate-to-severe AD does not increase risk of systemic or cutaneous infections. Rates of treatment-emergent infections, including skin infections, in the OLE for up to 5 years were low, compared with patients receiving placebo + TCS in a 1-year study. Serious infection rates remained low and stable over the 5-year OLE. This report reinforces the known long-term safety profile of dupilumab from an infection perspective. [ABSTRACT FROM AUTHOR]

Introduction/Background Pruritus is one of the essential features of atopic dermatitis (AD) and is consistently reported by patients as the most burdensome symptom of the disease. Itch not only impacts quality of life but also contributes to furthering AD pathogenesis through the itch-scratch cycle and additional breakdown of the epidermal barrier. A treat-to-target concept established goals to guide treatment with systemic therapies in AD, including those for itch.1-3 Objectives To assess onset and maintenance of optimal itch response according to the treat-to-target concept in adult patients with moderate-to-severe AD treated with dupilumab + concomitant topical corticosteroids (TCS). Methods LIBERTY AD CHRONOS (NCT02260986), a 52-week trial, enrolled patients aged ≥18 years with moderate-to-severe AD. Patients treated with dupilumab every 2 weeks + TCS or placebo + TCS were included in this post hoc analysis. Optimal itch response per the treat-to-target concept was defined as Peak Pruritus Numerical Rating Scale (PP-NRS) score of ≤4, achieved after 6 months of treatment1. We assessed time to optimal itch response, percentage of patients achieving optimal itch response, and maintenance of optimal itch response. For maintenance of optimal itch response, the total number and percentage of weeks with PP-NRS ≤4 were calculated for each patient, and maximum duration was assessed as the longest period of consecutive weeks with PP-NRS ≤4 for each patient. Results Median (interquartile range) PP-NRS score at baseline was 7.7 (6.6–8.5) for patients treated with dupilumab + TCS and 7.6 (6.3–8.6) for patients who received placebo + TCS. Median time (95% CI) to achieve optimal itch response was 29 (22–43) days for patients treated with dupilumab+ TCS and 64 (43–105) days for patients who received placebo + TCS (HR [95% CI] = 1.668 [1.292–2.153]; P < 0.0001). 61.3% of patients treated with dupilumab + TCS achieved optimal itch response at 6 months, compared with 26.7% of those who received placebo + TCS (P < 0.0001). Significantly more patients treated with dupilumab + TCS maintained optimal itch response than patients who received placebo + TCS through 52 weeks. In the dupilumab group, median (Q1–Q3) maintenance of optimal itch response was 40 (11–50) weeks, compared with 3 (0–23) weeks in the placebo group (P < 0.0001), which corresponds to 77.1% of the total study duration (52 weeks) in the dupilumab group, compared with 5.7% in the placebo group. Maximum consecutive duration with optimal itch response was also significantly longer in dupilumab-treated patients than in patients who received placebo (median [Q1–Q3]: 29.2 [4–50] weeks for dupilumab vs 2.0 [0–13] weeks for placebo; P < 0.0001). Conclusions Patients treated with dupilumab + TCS achieved optimal itch response rapidly and significantly faster than patients who received placebo + TCS; 29 days in dupilumab-treated patients compared with 64 days in those who received placebo. Significantly more patients treated with dupilumab + TCS achieved and maintained optimal itch response than patients who received placebo + TCS through 52 weeks. Dupilumab + TCS also led to a significantly longer maintenance of optimal itch response (40 weeks) compared with placebo + TCS (3 weeks). [ABSTRACT FROM AUTHOR]

Introduction/Background Tralokinumab is a high-affinity, fully human IgG4 monoclonal antibody that specifically targets interleukin-13, a key driver of atopic dermatitis (AD) disease progression. Clinical trials have shown that tralokinumab is efficacious in patients with moderate-to-severe AD and has a favorable safety profile, including a low frequency of adverse events such as conjunctivitis. Management of patients in routine clinical practice differs from those enrolled in clinical trials due to strict protocol criteria, and there is a lack of clinical data on tralokinumab use in the real-world setting. Objectives: TRACE is a real-world study in patients with AD, aiming to better understand the effectiveness, safety, and clinical use of tralokinumab in daily practice. Here, we describe baseline characteristics from the first patients enrolled into TRACE in Germany. Methods: TRACE is an observational, prospective, single-cohort study of adult patients with moderate-to-severe AD who are treated with tralokinumab, according to national approved labels. Eleven countries are participating in the study across Europe, North America and the Middle East. The primary objective is to assess changes in clinical signs and symptoms of AD in tralokinumab-treated patients. Secondary objectives are to investigate safety, quality of life, patient-reported outcomes and treatment adherence, among others. Results: Of the first 100 patients initiated on tralokinumab, the mean age (standard deviation [SD]) was 44.7 years (17.9) and 58% were male. Most patients had moderate-to-severe AD with a mean Investigator's Global Assessment (IGA) score of 3.5 (SD 0.7) and mean Eczema Area and Severity Index (EASI) of 22.5 (SD 12.9). Patients reported heavy symptomatic burden of disease; the mean eczema-related sleep numerical rating scale (NRS) was 5.6 (SD 2.9) and mean worst daily pruritus NRS was 6.2 (SD 2.7). Patients also reported a substantial impact on quality of life, demonstrated by a mean Dermatology Life Quality Index of 15.6 (SD 6.9). Overall, 79 patients were biologic-naïve and 19 were biologic-experienced (data missing; n=2). All biologic-experienced patients were previously treated with dupilumab, of whom most experienced one or more treatment failures. Reasons for switching from dupilumab included lack or loss of effectiveness, and adverse events, which most commonly included conjunctivitis. Conclusions: Initial findings showed that most adult patients with moderate-to-severe AD who were treated with tralokinumab were biologic-naïve, indicating tralokinumab is prescribed as firstline systemic treatment in real-world clinical practice, in line with European Dermatology Forum guidelines. The main reasons for switching from dupilumab were lack or loss of effectiveness, and adverse events, such as conjunctivitis, indicating the need for alternative biologic treatments such as tralokinumab. [ABSTRACT FROM AUTHOR]

Tralokinumab is a high-affinity, fully human IgG4 monoclonal antibody that specifically inhibits interleukin-13 (IL-13), a key driver of atopic dermatitis (AD) disease progression. Clinical trials have shown that tralokinumab is efficacious in patients with moderate-to-severe AD and has a favorable safety profile, including a low frequency of adverse events (AEs) such as conjunctivitis. However, management of patients in routine clinical practice differ from those enrolled in clinical trials due to strict inclusion/exclusion criteria, and there is currently a lack of clinical data on tralokinumab use in the real-world setting. TRACE is an observational cohort study of patients with AD, which aims to better understand the effectiveness, safety and clinical use of tralokinumab in the real-world setting. This study aims to describe baseline characteristics and initial insights from the first 100 patients enrolled into TRACE in Germany. TRACE is a longitudinal, prospective, new user, noncomparative, observational, single-cohort study, with primary data collection of adult patients with AD who are treated with tralokinumab, according to national approved labels. The study is taking place across countries in Europe, North America and the Middle East. The primary objective is to assess changes in clinical signs and symptoms of AD in tralokinumab-treated patients. Secondary objectives are to investigate safety, quality of life, patient-reported outcomes and adherence, among others. This analysis includes the first 100 patients enrolled from 39 sites across Germany. Of the first 100 patients in TRACE initiated on tralokinumab in Germany, the majority were males. Most patients had moderate-to-severe disease as indicated by their mean Investigator's Global Assessment score and mean Eczema Area and Severity Index. Patients reported heavy symptomatic burden of disease, as demonstrated by their mean eczema-related sleep numerical rating scale (NRS) and mean worst daily pruritus NRS. Patients also reported a substantial impact on quality of life, as demonstrated by mean Dermatology Life Quality Index. Overall, approximately 4/5 of the patients were biologic-naïve. All biologic-experienced patients were previously treated with dupilumab, of whom most experienced one or more treatment failures. Reasons for switching from dupilumab included lack or loss of efficacy, and AEs, which included mainly conjunctivitis. Initial findings from the first 100 patients from TRACE in Germany showed that the majority of adult patients with moderate-to-severe AD treated with tralokinumab were biologic-naïve, indicating that tralokinumab is prescribed as first-line systemic treatment in the real world, in line with European Dermatology Forum guidelines. Of patients who switched from dupilumab, the main reasons for switching were lack or loss of efficacy, and conjunctivitis, indicating the need for an alternative biologic treatment such as tralokinumab. [ABSTRACT FROM AUTHOR]

Lebrikizumab (LEB) is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. To report integrated safety information in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of eight clinical Phase 2 and 3 trials. These data include adult and adolescent patients who received at least one dose of study drug from a total of eight atopic dermatitis clinical trials: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and a Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. This analysis includes all placebo-controlled Week 0- to 16-safety data in patients treated with LEB 250 mg every 2 weeks (LEBQ2W, n = 783) compared with placebo (n = 404) known as ALL PC Weeks 0–16, and all patients who received at least one dose of LEB (n = 1720) known as ALL LEB. Conjunctivitis cluster is defined by MedDRA-preferred terms of conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis and giant papillary conjunctivitis. Exposure adjusted incidence rates (IR) are provided as per 100 patient-years. In ALL PC Weeks 0–16 analysis, the frequency of treatment-emergent adverse events (TEAE) was 49.2% in LEBQ2W (n = 384) compared with 53.1% in placebo (n = 215). The majority of TEAEs reported were mild or moderate in severity with 2.3% (n = 18) reported as severe in LEBQ2W and 4.4% (n = 18) in placebo. Serious adverse events (SAEs) were reported by 1.3% (n = 10) in LEBQ2W and 1.9% (n = 8) in placebo. No deaths reported in LEBQ2W and one death in placebo. The most frequently reported TEAE in LEBQ2W was conjunctivitis and in placebo was atopic dermatitis. Conjunctivitis cluster was reported by 8.5% (n = 67) in LEBQ2W and 2.5% (n = 10) in placebo. All conjunctivitis cluster events were mild or moderate. Injection site reactions (ISRs) were reported by 2.6% (n = 20) in LEBQ2W and 1.5% (n = 6) in placebo. Adverse events leading to discontinuation were reported by 2.3% (n = 18) in LEBQ2W and 1.4% (n = 6) in placebo. In ALL LEB, the frequency of TEAEs was 64.3% (n = 1106, IR: 137.9), with the majority being mild or moderate in severity. Severe TEAEs were reported by 5.3% (n = 91). The incidence rates of TEAE did not increase with duration of treatment exposure. The SAEs were reported by 3.3% (n = 56, IR: 3.5). Three (0.2%) deaths occurred in ALL LEB. Conjunctivitis cluster was reported by 10.6% (n = 183, IR:12.2) with the majority being mild or moderate in severity and 0.3% (n = 6) being reported as severe. The ISRs were reported by 3.1% (n = 53, IR: 3.3). Adverse events leading to discontinuation were reported by 4.2% (n = 73, IR: 4.5). The overall safety profile for lebrikizumab consisted of AEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. Safety profile was similar in both adults and adolescents. [ABSTRACT FROM AUTHOR]