BACKGROUND:In patients with moderate atopic dermatitis (AD), topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) often do not sufficiently control AD signs/symptoms, and escalation to systemic therapy may be required. OBJECTIVES:Report 8-week results of ruxolitinib cream in TRuE-AD4 (NCT06238817) in patients with moderate AD who had an inadequate response/intolerance/contraindication to TCS and TCI in the past 12 months (post-TCS and -TCI). METHODS:Patients aged ≥18 years with AD, an Investigator's Global Assessment (IGA) of 3, Eczema Area and Severity Index (EASI) >7, itch numerical rating scale (NRS) ≥4, 10%-20% affected body surface area and Dermatology Life Quality Index score > 10 post-TCS and -TCI were randomized (2:1) to twice-daily 1.5% ruxolitinib cream or vehicle for 8 weeks. Coprimary endpoints at Week 8 were ≥75% improvement in EASI from baseline (EASI-75) and IGA score of 0/1 with a ≥ 2-point improvement from baseline (IGA treatment success [TS]). RESULTS:Of 241 randomized patients (mean age, 37.0 y; 54.4% female), mean EASI and itch NRS scores were 12.6 and 7.4, respectively, at baseline. At Week 8, significantly more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (61.3% vs. 13.6%; p < 0.0001) and EASI-75 (70.0% vs. 18.5%; p < 0.0001). Significantly more patients achieved a ≥ 4-point improvement in itch NRS (itch NRS4) at Day 2 (29.8% vs. 13.7%; p = 0.0072); improvement in current itch (no recall) was observed in 15 min after the first application. No treatment-related adverse events were serious, and the most common adverse event occurring with ruxolitinib cream was application site acne (3.8%). CONCLUSIONS:In adults with moderate AD post-TCS and -TCI, who may otherwise be eligible for systemic therapy, 1.5% ruxolitinib cream significantly improved clinical signs of AD, rapidly improved itch and was well tolerated. Thus, ruxolitinib cream may represent an effective topical option before escalation to systemic therapy in patients with moderate AD.

BACKGROUND:Rezpegaldesleukin is an interleukin-2 receptor agonist that selectively expands and enhances the function of regulatory T cells (Tregs), offering a novel therapeutic approach for autoimmune and inflammatory diseases such as atopic dermatitis. We aimed to compare the efficacy and safety analyses of rezpegaldesleukin with placebo in adults with moderate-to-severe atopic dermatitis naive to biological treatments. METHODS:REZOLVE-AD was a phase 2b, randomised, double-blind, placebo-controlled study conducted in 107 community research centres or hospitals in ten countries (Australia, Bulgaria, Canada, Croatia, Czechia, Germany, Hungary, Poland, Spain, and the USA). Eligible patients were adults (aged 18 years or older) with confirmed atopic dermatitis (American Academy of Dermatology Consensus Criteria) diagnosed at least 12 months before enrolment, with moderate-to-severe disease activity defined by an Eczema Area and Severity Index (EASI) score of at least 16·0, validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of at least 3 (moderate), and at least 10% affected body surface area. Patients were randomly allocated (3:3:3:2) to receive subcutaneous rezpegaldesleukin 24 μg/kg or rezpegaldesleukin 18 μg/kg every 2 weeks, rezpegaldesleukin 24 μg/kg every 4 weeks, or placebo for 16 weeks during the induction period. Randomisation was done by an independent vendor using Randomisation and Trial Supply Management methodology via an interactive response system and was stratified by baseline disease severity (vIGA-AD 3 [moderate] vs 4 [severe]) and geographical region (North America vs rest of world). All patients, investigators, and those assessing outcomes were masked to treatment assignment. Outcomes for the induction period were assessed through week 16 and are included in this report. The primary endpoint was percentage change from baseline in EASI score at week 16. Efficacy and safety analyses were conducted in all randomly assigned patients exposed to study treatment, excluding those enrolled at two sites closed due to Good Clinical Practice non-compliance, both of which received notification of closure approximately 300 days before database lock. All missing data were imputed with multiple imputation. The trial was registered with ClinicalTrials.gov (NCT06136741). FINDINGS:398 patients were enrolled between Nov 15, 2023, and Jan 9, 2025. A total of 393 patients were analysed (104 in the rezpegaldesleukin 24 μg/kg every 2 weeks group, 106 in the rezpegaldesleukin 18 μg/kg every 2 weeks group, 110 in the rezpegaldesleukin 24 μg/kg every 4 weeks group, and 73 in the placebo group); 203 (52%) patients were female and 190 (48%) were male. All three rezpegaldesleukin groups met the primary endpoint. Rezpegaldesleukin showed dose-dependent improvements compared with placebo in mean percentage change in EASI from baseline at week 16: -61% (SE 3·8) for rezpegaldesleukin 24 μg/kg every 2 weeks, -58% (3·8) for rezpegaldesleukin 18 μg/kg every 2 weeks, and -53% (3·7) for rezpegaldesleukin 24 μg/kg every 4 weeks versus -31% (4·5) for placebo. Treatment differences versus placebo were -30 percentage points (95% CI -41·3 to -18·0; p<0·0001) for rezpegaldesleukin 24 μg/kg every 2 weeks, -27 percentage points (-38·5 to -15·7; p<0·0001) for rezpegaldesleukin 18 μg/kg every 2 weeks, and -22 percentage points (-33·3 to -10·3; p=0·0002) for rezpegaldesleukin 24 μg/kg every 4 weeks. Treatment-emergent adverse events observed in at least 5% of rezpegaldesleukin-treated patients (n=320) and greater than placebo (n=73) included injection-site reaction (223 [70%] vs three [4%]), eosinophilia (25 [8%] vs two [3%]), pyrexia (20 [6%] vs two [3%]), headache (20 [6%] vs three [4%]), upper respiratory tract infections (19 [6%] vs four [5%]), and arthralgia (16 [5%] vs one [1%]). Nearly all (>99%) injection-site reactions were mild to moderate in severity and resolved. There was no evidence of an increased risk of serious or severe adverse events, and no deaths were reported during the induction period. INTERPRETATION:Over the 16-week induction period, rezpegaldesleukin treatment resulted in significant and clinically meaningful improvements across multiple clinical endpoints, including the primary endpoint of EASI percentage change from baseline, in comparison with placebo. Rezpegaldesleukin had a clinically favourable adverse event profile in adult patients with moderate-to-severe atopic dermatitis, supporting its further development as a novel Treg-enhancing biological treatment. FUNDING:Nektar Therapeutics.

Nemolizumab with background topical therapy (corticosteroids±calcineurin inhibitors) significantly improved skin lesions, itch and sleep in two global phase 3 trials (ARCADIA 1&2) in adolescents and adults with moderate-to-severe atopic dermatitis through week (W)16. Efficacy and safety of nemolizumab, combined with background topical therapy, were evaluated for an additional 32 weeks (W16–W48) with a focus on maintained skin responses in clinical responders (patients achieving Investigator’s Global Assessment [IGA] score of 0/1 [clear/almost clear] or ≥75% improvement in Eczema Area and Severity Index [EASI-75] at W16). At W16, clinical responders (N=507) to nemolizumab every 4 weeks (Q4W) were rerandomized (1 : 1 : 1) to receive nemolizumab 30 mg-Q4W/-Q8W/placebo (nemolizumab-withdrawal) subcutaneously with background topical therapy. At W48, 61.5% (strata-adjusted difference versus nemolizumab-withdrawal group [Δ], 11.8% [95% CI 1.3–22.3]) and 76.3% (Δ, 12.4% [95% CI 2.7– 22.0]) of patients in nemolizumab-Q4W; 60.4% (Δ, 10.7% [95% CI 0.3–21.0]) and 75.7% (Δ, 11.8% [95% CI 2.1–21.5]) in nemolizumab-Q8W; and 49.7% and 63.9% in nemolizumab-withdrawal group maintained response rate for IGA success and EASI-75, respectively. The percentage of patients who experienced ≥1 adverse events were similar across the groups (range: 53.5%–58.3%). Up to W48, skin responses were maintained without notable differences in the safety profile of both nemolizumab dosing regimens.

Nemolizumab with background topical therapy (corticosteroids +/- calcineurin inhibitors) significantly improved skin lesions, itch and sleep in two global phase 3 trials (ARCADIA 1&2) in adolescents and adults with moderate-to-severe atopic dermatitis through week (W)16. Efficacy and safety of nemolizumab, combined with background topical therapy, were evaluated for an additional 32 weeks (W16-W48) with a focus on maintained skin responses in clinical responders (patients achieving Investigator's Global Assessment [IGA] score of 0/1 [clear/almost clear] or >= 75% improvement in Eczema Area and Severity Index [EASI-75] at W16). At W16, clinical responders (N=507) to nemolizumab every 4 weeks (Q4W) were rerandomized (1 : 1 : 1) to receive nemolizumab 30 mg-Q4W/-Q8W/placebo (nemolizumab-withdrawal) subcutaneously with background topical therapy. At W48, 61.5% (strata-adjusted difference versus nemolizumab-withdrawal group [Delta], 11.8% [95% CI 1.3-22.3]) and 76.3% (Delta, 12.4% [95% CI 2.7- 22.0]) of patients in nemolizumab-Q4W; 60.4% (Delta, 10.7% [95% CI 0.3-21.0]) and 75.7% (Delta, 11.8% [95% CI 2.1-21.5]) in nemolizumab-Q8W; and 49.7% and 63.9% in nemolizumab-withdrawal group maintained response rate for IGA success and EASI-75, respectively. The percentage of patients who experienced >= 1 adverse events were similar across the groups (range: 53.5%-58.3%). Up to W48, skin responses were maintained without notable differences in the safety profile of both nemolizumab dosing regimens.

Abstract Self-stigmatization and concerns about body appearance are prevalent among people living with chronic skin disease, which can severely impact on their mental health and quality of life. As few online approaches targeting psychosocial needs of patients with skin disease are available, we developed a web-based programme based on cognitive behavioural therapy and self-­compassion approaches. This parallel group-randomized controlled trial (registration: NCT06324695) examined the effectiveness of the programme in reducing self-stigma, and enhancing acceptance coping and self-compassion. We expected larger reductions in self-stigma, depression, anxiety and avoidance, as well as greater increases in acceptance coping, self-compassion and positive body image from pre- to postintervention and at the 6-month follow-up in the intervention group compared with the control group. German-speaking adults (n = 284) with alopecia areata, atopic dermatitis, hidradenitis suppurativa, psoriasis or and vitiligo were randomized 1 : 1 into an intervention group (n = 151), which worked through the eight self-guided modules, or a waitlist control group (n = 133). Self-stigma, self-compassion, acceptance and other psychosocial variables were assessed by self-report questionnaires before and after the programme, and at the 6-month follow-up. Data were analysed using generalized linear mixed models. There were significant differences between groups in self-stigma [F(1,169) = 13.4; P < 0.001], anxiety [F(1,168) = 5.17; P = 0.02] and acceptance [F(1,179) = 7.27; P = 0.008] from before to after the programme to the 6-month follow-up, with patients in the intervention group showing greater reductions in self-stigma and anxiety, and greater improvements in acceptance compared with those in the control group. Change scores in self-compassion did not differ between the two groups [F(1,180) = 2.77, P = 0.10]. The web-based programme demonstrated effectiveness in reducing self-stigma and enhancing acceptance among people living with chronic skin diseases. As the first intervention of its kind available in German, it marks a significant step forward in psychosocial care in dermatology.

Purpose:Psoriasis lesions in the anogenital area affect about 33%-63% of the patients at some point in the disease course. Diminished quality of life (QoL), high depression rates, and sexual impairments have been described among patients with anogenital psoriasis, but specific treatment needs of these patients are often neglected in routine healthcare. This study aimed to compare patients with vs. without current anogenital lesions in terms of their sociodemographic and clinical characteristics, patient-reported outcomes (PROs) of disease burden, and patient-defined treatment needs/benefits and to identify clinical variables associated with PROs of disease burden. Patients and Methods:The study had a cross-sectional case-control design. Patients aged ≥ 18 years with psoriasis were consecutively recruited in four German dermatology centers and were assigned to case or control group based on both patients' and physicians' reports of current anogenital involvement. PROs included the assessment of QoL impairments, treatment needs/benefits, depression/anxiety, perceived stigmatization, sexual frequency, and relationship/sexual impairments. Physicians assessed the severity of psoriasis and anogenital lesions (PASI and sPGA-G). Results:Participants were 294 patients with psoriasis, of which 159 (54.1%) had current anogenital lesions. Patients with anogenital lesions had higher disease severity, more comorbidities, but were less often treated with biologics. They also reported more QoL impairments, less treatment benefits, poorer mental health, and more sexual impairments. Specific treatment needs of patients with anogenital psoriasis were related to reducing physical and relationship/sexual impairments. Poorer PROs were explained at 25%-68% by higher disease severity, anogenital lesions, no biologic treatment, higher intensity of itching/burning, and lower frequency and more limitations in sexual activity. Conclusion:Within a patient-centered approach to dermatology care for psoriasis, clinical decisions, particularly patients' qualification for treatment with biologic drugs, should consider not only the location, extent, and severity of psoriasis lesions but also patient-reported symptoms, overall disease burden, and sexual limitations.

Chronic inflammatory skin conditions significantly impact the quality of life (QoL) of those affected. Itch is a cardinal symptom in many of these conditions, contributing decisively to the burden of disease. This cross-sectional study explored how itch and related factors mediate the relationship between disease severity and QoL impairment. Adult patients with chronic pruritus arising from psoriasis, atopic dermatitis, chronic prurigo, or chronic urticaria completed a set of validated questionnaires assessing worst and average itch intensity (worst itch intensity on the numerical rating scale [WI-NRS]/average itch intensity on the numerical rating scale [AI-NRS]), impairment of QoL with the 5-pruritus life quality (5PLQ), daily time with itch, scratching frequency, and sleep disturbance. Disease severity was evaluated using validated disease-specific scales. Spearman’s rank correlation was performed to assess intercorrelations between 5PLQ scores, disease severity, and itch-related factors. A linear regression analysis investigated associations of 5PLQ with demographic and clinical factors. Mediation analyses examined whether the link between disease severity and 5PLQ scores was mediated by itch intensity, daily itch duration, scratching frequency, and sleep disturbance. A total of 522 patients (282 female, median age: 56.0 years) participated in the study. 5PLQ scores correlated weakly with disease severity (r = 0.201, p < 0.001), and strongly with itch-related factors (r = 515–0.603, p < 0.001). The linear regression analysis revealed a positive association between 5PLQ scores and female sex (β: 0.887, p = 0.003), moderate disease severity (β: 1.552, p = 0.032), scratching frequency (β: 0.370, p < 0.001), and sleep disturbance (β: 0.427, p < 0.001). Mediation analyses showed that the association between disease severity and QoL impairment was partially mediated by average itch intensity (indirect β: 0.168, p = 0.049), daily itch duration (indirect β: 0.270, p < 0.001), scratching frequency (indirect β: 0.205, p = 0.010), and sleep disturbance (indirect β: 0.235, p = 0.006). Average itch intensity, daily itch duration, scratching, and sleep disturbance mediate the relationship between disease severity and impairment of QoL. Interventions targeting these aspects of disease may improve patient outcomes. Chronic inflammatory skin conditions are highly prevalent in our society, contributing to substantial impairment of quality of life. Itch is the major symptom associated with these diseases, impacting the daily activities and sleep of those affected. We enrolled 522 patients with chronic itch arising from common inflammatory skin condition (atopic dermatitis, psoriasis, prurigo, or urticaria) at two clinics and ten dermatological offices across the states of North Rhine-Westphalia and Lower Saxony in Germany to study how itch-related factors explain the known relationship between disease severity and impairment of quality of life. Patients completed a set of questionnaires inquiring about various aspects of itch (including intensity, daily time with itch, scratching frequency, sleep disturbance), as well as impairment of quality of life. A dermatologist assessed disease severity on the basis of the skin examination. We observed significant associations between disease severity, itch-related factors, and impairment of quality of life. The amount of time patients experienced itch in a day was the factor that most strongly explained how disease severity led to an impaired quality of life. The degree of sleep disturbance was the next most important factor, followed by how often patients scratched and average itch intensity but not peak itch episodes. These results highlight that different aspects of itch play a role in reducing quality of life in patients with inflammatory skin diseases. It is therefore of great importance to assess these factors in routine care. Treatments that target these dimensions of itch may improve care and well-being in this patient population.

Tildrakizumab, an anti-IL-23p19 antibody, is registered for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Its effectiveness in specific patient subgroups—e.g. those with high body weight, high disease burden, involvement of high-impact areas or older patients—is often underrepresented in randomised clinical trials and better captured in real-world settings. To address this gap, the present meta-analysis was undertaken to synthesise data from four observational studies conducted in Germany (TILOT, TiGER, TIL-SENIOR, TIL-TWO), each focusing on distinct psoriasis populations. This meta-analysis of four prospective multicentre non-interventional studies evaluated the effectiveness and safety of tildrakizumab in different patient populations with moderate-to-severe plaque psoriasis. Outcome parameters assessed at baseline, week 16 and 28 included absolute Psoriasis Area Severity Index (PASI) values, proportion of patients with PASI < 1, < 3, < 5, PASI 75, PASI 90 and PASI 100, body surface area (BSA), Physician’s Global Assessment (PGA) 0/1 and Dermatology Life Quality Index (DLQI) 0/1. The meta-analysis was conducted using a random effects model. The meta-analysis included 1504 patients. The course of the absolute PASI and BSA and the proportion of patients achieving PASI < 3, PASI 75, 90, 100, PGA 0/1 and DLQI 0/1 at week 28 was comparable across all four studies. Overall, mean PASI scores decreased from 16.5 (95

Zusammenfassung Hintergrund und Ziele Psoriasis vulgaris ist eine chronisch entzündliche Hauterkrankung, die mit zahlreichen kardiovaskulären Begleiterkrankungen und letztlich erhöhter Sterblichkeit einhergehen kann. Dermatologische Rehabilitationsprogramme sind neben der klassischen ambulanten Versorgung oder der akutstationären Behandlung eine zusätzliche therapeutische Option für Patienten mit Psoriasis. Diese Studie zielte darauf ab, die Auswirkungen einer dermatologischen Rehabilitation auf kardiovaskuläre Risikofaktoren, kardiorespiratorische Fitness und Lebensqualität in der Klinik für Dermatologie und Allergologie des Medizinischen Rehabilitationszentrums Bad Bentheim, Deutschland, zu untersuchen. Patienten und Methodik Diese prospektive Studie umfasste 105 Patienten (Alter > 18) mit bekannter Psoriasis und/oder Psoriasis (pustulosa) palmoplantaris, die sich einem dreiwöchigen Rehabilitationsprogramm unterzogen. Verschiedene patientenbezogene Ergebnisse, einschließlich Dermatologic Life and Quality Index (DLQI), Patient Global Assessment (PtGA) , körperliche Aktivität, Pruritus sowie Nikotin‐ und Alkoholkonsumanamnese wurden erfasst. Darüber hinaus wurden der Body‐Mass‐Index (BMI) und die körperliche Fitness bewertet. Die Studienparameter wurden bei Aufnahme, Entlassung vor Ort und nach 3 und 6 Monaten telefonisch erhoben. Ergebnisse Signifikante Verbesserungen der kardiorespiratorischen Fitness (p < 0,001), des Body‐Mass‐Index (p < 0,001), der Lebensqualität (p < 0,001), der subjektiven Einschätzung der Krankheitsaktivität durch den Patienten (p < 0,001) sowie des Psoriasis Area and Severity Index (PASI) (p < 0,001) wurden festgestellt. Schlussfolgerungen Die Ergebnisse unterstreichen die Bedeutung eines Rehabilitationsprogramms für Patienten mit Psoriasis aufgrund seiner positiven und nachhaltigen Auswirkungen auf kardiovaskuläre Risikofaktoren.

BACKGROUND:Monoclonal antibodies targeting interleukin-23 and interleukin-12 are efficacious in treating plaque psoriasis but must be delivered via intravenous or subcutaneous injection. Here, we aimed to evaluate the efficacy and safety of icotrokinra (JNJ-77242113), a targeted oral peptide that selectively binds the interleukin-23 receptor, compared with both placebo and deucravacitinib in adults with moderate-to-severe plaque psoriasis. METHODS:The phase 3, randomised, double-blind, placebo-controlled and active-comparator-controlled ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2 trials, which are being done at 149 sites across 13 countries and 114 sites across 11 countries, respectively, randomly assigned (2:1:2 and 4:1:4, respectively) adults with moderate-to-severe plaque psoriasis diagnosed for at least 26 weeks (body-surface-area involvement ≤10%, Psoriasis Area and Severity Index [PASI] ≤12, and Investigator's Global Assessment [IGA] ≤3) to once-daily oral icotrokinra 200 mg, placebo, or deucravacitinib 6 mg; participants randomly assigned to placebo or deucravacitinib transitioned to icotrokinra at week 16 or week 24, respectively. Coprimary endpoints were proportions of participants achieving IGA 0 or 1 (clear or almost clear skin) with at least a two-grade improvement and at least 90% improvement in PASI (PASI 90) at week 16 with icotrokinra versus placebo. These studies are registered with ClinicalTrials.gov, NCT06143878 (ADVANCE 1) and NCT06220604 (ADVANCE 2), and are ongoing. FINDINGS:ICONIC-ADVANCE 1 enrolled participants from Jan 17, 2024, to May 24, 2024, and ICONIC-ADVANCE 2 enrolled participants from March 9, 2024, to June 13, 2024. Participants (ADVANCE 1: 774 of 988 patients screened; ADVANCE 2: 731 of 917 patients screened) were randomly assigned to icotrokinra (n=311 and 322), placebo (n=156 and 82), or deucravacitinib (n=307 and 327). All coprimary endpoints were met in both trials. Higher proportions of icotrokinra-treated versus placebo-treated participants achieved IGA 0 or 1 (ADVANCE 1: 213 [68%] of 311 vs 17 [11%] of 156, treatment difference 95% CI 58% [50-64]; ADVANCE 2: 227 [70%] of 322 vs seven [9%] of 82, 62% [53-69]; both p<0·0001) and PASI 90 (ADVANCE 1: 171 [55%] of 311 vs six [4%] of 156, treatment difference 95% CI 51% [44-57]; ADVANCE 2: 184 [57%] of 322 vs one [1%] of 82, 56% [48-62]; both p<0·0001) at week 16. Across studies, adverse event rates to week 16 were 303 (48%) of 632 and 136 (57%) of 237 with icotrokinra and placebo, respectively; the most common adverse events were nasopharyngitis (37 [6%] of 632 and 13 [5%] of 237) and upper respiratory tract infection (23 [4%] of 632 and eight [3%] of 237). To week 24, adverse event rates were lower than with icotrokinra (359 [57%] of 632) than deucravacitinib (411 [65%] of 634). INTERPRETATION:Icotrokinra showed superior clinical response rates versus placebo and deucravacitinib in phase 3 moderate-to-severe plaque psoriasis trials, with similar adverse event rates to placebo. These findings suggest the potential of once-daily oral icotrokinra to provide robust efficacy and a favourable safety profile. FUNDING:Johnson & Johnson.

BACKGROUND:ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA). OBJECTIVES:To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss. METHODS:ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study. The de novo cohort results are reported here. Patients aged ≥12 years with AA and ≥25% scalp hair loss received a daily, 4-week 200-mg ritlecitinib loading dose, followed by daily 50-mg ritlecitinib. Analyses are based on data up to the cut-off (December 2022). Efficacy outcomes included proportions of patients achieving Severity of Alopecia Tool (SALT) scores ≤20 and ≤10, Patient Global Impression of Change (PGI-C) score of 'moderately improved' or 'greatly improved' and eyebrow assessment (EBA) and eyelash assessment (ELA) response (≥2-grade improvement from baseline or normal score in patients with abnormal baseline EBA/ELA). RESULTS:Mean (SD) ritlecitinib exposure among the 449 de novo patients enrolled was 728.7 (273.81) days. At Month 24 (as observed), 73.5% and 66.4% of patients achieved SALT score ≤20 and ≤10; 82.4% had PGI-C response; 60.8% and 65.7% had EBA and ELA response. 86.1% of patients reported treatment-emergent adverse events (AEs); most were mild or moderate in severity, with the most frequent being positive SARS-CoV-2 test (24.2%), headache (20.8%) and pyrexia (13.0%). Rates of serious AEs, severe AEs and treatment discontinuations were 4.9%, 6.0% and 6.5%, respectively. Herpes zoster infection occurred in six patients, serious infections in four, malignancies (excluding nonmelanoma skin cancer) in three and major adverse cardiovascular events in three. CONCLUSIONS:In patients with AA and ≥25% scalp hair loss, ritlecitinib demonstrated clinical efficacy and had an acceptable safety profile with long-term treatment. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov NCT04006457.

Ciclosporin A (CsA) is indicated for the treatment of severe atopic dermatitis (AD), but its efficacy may not be optimal and its safety limits longer-term use. Lebrikizumab (LEB) is a high-affinity anti-interleukin-13 monoclonal antibody. In the ADvantage study (NCT05149313), LEB was dosed 250 mg every 2 weeks and administered with topical corticosteroids (TCS). At week 16 this regimen had significantly improved signs and symptoms of AD in adults and adolescents with moderate-to-severe AD inadequately controlled or ineligible for CsA, with an acceptable safety profile. The objective of this study was to assess the quality of life (QoL) at week 16 of patients with moderate-to-severe AD inadequately controlled with or ineligible for CsA. ADvantage is a 52-week study with a 16-week placebo (PBO)-controlled induction period plus a 36-week open-label maintenance period with LEB dosed every 2 weeks. Eligible patients were adults and adolescents (≥ 12 to < 18 years) with Eczema Area and Severity Index ≥ 16, Investigator’s Global Assessment ≥ 3, and ≥ 10% body surface area of AD involvement, not adequately controlled with or ineligible for CsA. Patients received concomitant low-to-mid-potency topical corticosteroids (TCS) through week 16. QoL was assessed by Dermatology Life Quality Index (DLQI). Here we report different endpoints: the percentage change from baseline (CFB), the percentage of patients achieving DLQI ≤ 5 and the percentage of patients achieving DLQI of 0 or 1 (0/1). Missing data due to lack of efficacy or data after rescue medication usage (high-potency TCS or systemic treatment) were imputed using nonresponder imputation. Other missing data were imputed using multiple imputation. Descriptive analyses of percentage CFB in DLQI were performed by mixed models for repeated measures. In total, 331 patients were randomized (220 LEB+TCS and 111 PBO+TCS) and 212 and 100, respectively, completed the 16-week period. The treatment groups had similar baseline characteristics. A greater percentage CFB in DLQI was obtained with LEB)TCS than PBO+TCS (−59.9% vs. −37.3%, P < 0.01) at week 16. Moreover, a higher percentage of patients on LEB+TCS achieved DLQI ≤ 5 (55.7% LEB+TCS vs. 34.7% PBO+TCS, P < 0.05) and DLQI 0/1 (30.6% LEB+TCS vs. 8.3% PBO+TCS, P < 0.001) at week 16, compared with PBO+TCS. LEB dosed every 2 weeks with TCS showed improvements in the QoL of adults and adolescents with moderate-to-severe AD inadequately controlled with or ineligible for CsA. A relevant number of patients reported no or minimal impact on their QoL after 16 weeks of treatment. Almirall, S.A. has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe. Lilly has exclusive rights for the development and commercialization of lebrikizumab in the USA and the rest of the world outside of Europe. Medical writing was funded by Almirall S.A.

BACKGROUND:Prurigo nodularis (PN) is a neuroimmune skin disease characterized by the presence of chronic itch (≥6 weeks) and multiple white-pink papules, nodules and/or plaques. OBJECTIVES:The OLYMPIA long-term extension (OLYMPIA-LTE) trial evaluates long-term, over 184 weeks, safety and efficacy of nemolizumab in adults with moderate-to-severe PN. METHODS:Adults with moderate-to-severe PN, who completed phase 2b (NCT03181503) and phase 3 (OLYMPIA 1&2) lead-in trials, were eligible for the ongoing OLYMPIA-LTE trial. Patients receiving nemolizumab monotherapy (continuous-nemolizumab) during lead-in trials continued their regimen, while those on placebo (nemolizumab-naïve) initiated nemolizumab monotherapy. The primary endpoint was long-term safety. Efficacy assessments included the proportion of patients achieving a ≥4-point improvement from baseline Peak Pruritus Numerical Rating Scale (PP-NRS4), Sleep Disturbance Numerical Rating Scale (SD-NRS4) and Dermatology Life Quality Index (DLQI4) scores, Investigator's Global Assessment (IGA) score 0/1 (clear/almost clear), and 75% healed pruriginous lesions (Prurigo Activity and Severity score item-5b). Observed cases up to week 100, regardless of rescue medication, are presented, without imputation of missing data. RESULTS:At interim analysis data cut-off (21 July 2024), 290/508 (57%) patients completed week 100 (median exposure: 839.5 days). Treatment-emergent adverse events (TEAEs) occurred in 89% of patients (452/508; exposure time-adjusted incidence rate: 197.5/100 patient-years) and were mostly mild/moderate (26%/52%) in severity. TEAEs occurring in ≥5% of patients at any given year were COVID-19 (28%), nasopharyngitis (20%), upper respiratory tract infection (13%), neurodermatitis (worsening of PN; 13%), back pain (9%), headache (9%), arthralgia (9%), cough (8%), hypertension (8%) and nummular eczema (8%). At week 100, among evaluable patients treated with nemolizumab, 92% achieved PP-NRS4, 86% SD-NRS4, 91% DLQI4, 74% IGA 0/1 and 84% observed healing of >75% of pruriginous lesions. CONCLUSIONS:Long-term treatment with nemolizumab was well tolerated and led to disease control with clinically meaningful improvements in itch intensity, pruriginous lesions and quality of life. CLINICAL TRIAL REGISTRATION NO:NCT04204616, RD.06.SPR.202699 and 2019-004294-13 (EudraCT Number).

BACKGROUND:Pivotal clinical trials have assessed the efficacy and safety of fixed-dose upadacitinib 15 mg (UPA15) and 30 mg (UPA30) once daily in atopic dermatitis (AD). OBJECTIVES:To assess the efficacy and safety of dose escalation to UPA30 and dose reduction to UPA15 based on a clinical response [90% reduction in Eczema Area and Severity Index (EASI 90)] after 12 weeks of treatment in adults with moderate-to-severe AD enrolled in a randomized blinded treat-to-target multicentre phase IIIb/IV study. METHODS:A total of 461 patients were randomized in a 1 : 1 ratio to receive oral doses of UPA15 (n = 229) or UPA30 (n = 232) once daily during the 12-week double-blinded period. At week 12, patients on UPA15 not achieving EASI 90 were dose escalated to UPA30 (UPA15/30); patients achieving ≥ EASI 90 continued on UPA15 (UPA15/15). Patients on UPA30 not achieving EASI 90 at week 12 continued on UPA30 (UPA30/30); patients achieving ≥ EASI 90 received a reduced dose of UPA15 (UPA30/15) for 12 additional weeks. The primary efficacy endpoint was EASI 90 achievement at week 24. Results were reported descriptively as observed. Safety outcomes were assessed. RESULTS:At week 24, of patients who received dose escalation (UPA15/30), 48.1% [n = 64/133; 95% confidence interval (CI) 39.6-56.6] achieved EASI 90; of patients who received a dose reduction (UPA30/15), 68.5% (n = 89/130; 95% CI 60.5-76.4) maintained EASI 90. Of patients who continued on their initial dose, 29.3% (n = 24/82; 95% CI 19.4-39.1) on UPA30/30 achieved EASI 90 and 74.6% (n = 53/71; 95% CI 64.5-84.8) on UPA15/15 maintained EASI 90. At week 24, 32.5% (n = 27/83; 95% CI 22.5-42.6) and 38.0% (n = 38/100; 95% CI 28.5-47.5) of patients on UPA15/30 and UPA30/15, respectively, achieved a worst pruritus numerical rating scale score of 0 or 1 (WP-NRS 0/1), and 20.7% (n = 17/82; 95% CI 12.0-29.5) and 35.0% (n = 35/100; 95% CI 25.7-44.3), respectively, achieved combined EASI 90 and WP-NRS 0/1. At week 24, treatment emergent adverse events were reported in 43.1% (n = 31/72; UPA15/15), 54.2% (n = 78/144; UPA15/30), 61.5% (n = 56/91; UPA30/30) and 48.9% (n = 65/133; UPA30/15) of patients. No malignancies, adjudicated venous thromboembolic events or deaths were reported. CONCLUSIONS:Treatment of moderate-to-severe AD with UPA15 or UPA30, with dose escalation or dose reduction based on achievement of the optimal treatment target of EASI 90 at week 12, demonstrated that both approaches support the achievement and maintenance of EASI 90 at week 24. Overall safety findings were consistent with the known UPA safety profile, with no new safety signals identified.

Lebrikizumab (LEB), a high-affinity anti-interleukin-13 monoclonal antibody, showed efficacy and safety in patients with moderate-to-severe atopic dermatitis (AD). Ciclosporin A (CsA) is indicated for severe AD, but its efficacy may not be optimal and its safety limits longer-term use. The objective of this study was to assess the quality of life (QoL) and wellbeing of patients with moderate-to-severe AD receiving LEB. Eligible patients were inadequately controlled with or ineligible for CsA and were followed up to week 76 (German extension of the ADvantage study, NCT05149313). ADvantage is a 52-week study with a 16-week placebo (PBO)-controlled induction period plus a 36-week open-label maintenance period with LEB dosed every 2 weeks. Eligible patients were adults and adolescents (≥ 12 to < 18 years) with Eczema Area and Severity Index ≥ 16, Investigator’s Global Assessment ≥ 3, and ≥ 10% body surface area of AD involvement, and not adequately controlled with or not eligible for CsA. Patients received concomitant low-to-mid-potency topical corticosteroids (TCS) through week 16; from W16 onwards TCS use was at investigator discretion. Patients who completed the 52-week maintenance period were eligible to join the extension-period, to continue LEB every 4 weeks for a minimum of 24 additional weeks (German extension). QoL was assessed as the percentage of change from baseline in the Dermatology Life Quality Index (DLQI) score. From week 0 to week 16, Ancova models were applied, and from week 16 to week 76, analyses were performed as observed. Wellbeing was assessed through the five-item WHO Well-being Index (WHO-5). WHO-5 has a range of 0–100, with 100 representing maximal wellbeing. The mean WHO-5 score in the German general population was 64.7, with a score of 52.2 in women with breast cancer and 51.4 in patients with diabetes with distress. Analyses were performed as observed. In total, 43 patients were included. At week 16 the change in DLQI from baseline was −78.0% (n = 31) for LEB every 2 weeks + TCS, and −59.2% (n = 12) for PBO every 2 weeks + TCS. At week 52 (LEB every 2 weeks ± TCS) the change in DLQI from baseline was −77.1% (n = 38), and at week 76 (LEB every 4 weeks ± TCS) it was −78.9% (n = 29). At baseline, the mean WHO-5 score was 40.1 (n = 28) in patients in the LEB arm and 35 (n = 12) in patients on PBO. At week 16 these scores had increased to 61.7 (n = 28) in patients treated with LEB every 2 weeks + TCS and 51.7 (n = 12) in those treated with PBO every 2 weeks + TCS. From week 16, the WHO-5 scores remained stable: at week 52 it was 60.9 (n = 28) in patients with LEB every 2 weeks ± TCS, and at week 76 it was 61.7 (n = 30) in patients treated with LEB every 4 weeks ± TCS. In the German extension population with moderate-to-severe AD inadequately controlled with or ineligible for CsA, LEB showed improvements in QoL and wellbeing up to week 76. Almirall, S.A. has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including AD, in Europe. Lilly has exclusive rights for the development and commercialization of lebrikizumab in the USA and the rest of the world outside of Europe. Medical writing was funded by Almirall S.A.