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Introduction: Ritlecitinib demonstrated efficacy in patients with alopecia areata (AA) in the ALLEGRO phase 2b/3 study (NCT03732807). However, hair loss presentation may vary based on location (e.g., scalp, eyebrow/eyelash, body). Here, we sought to identify distinct hair loss profiles at baseline and evaluate whether they affected the efficacy of ritlecitinib. Methods: Patients with AA aged ≥ 12 years with ≥ 50% scalp hair loss were randomized to daily ritlecitinib 10 mg (assessed for dose ranging only), 30 or 50 mg (± 4-week, 200-mg loading dose), or placebo for 24 weeks. Latent class analysis (LCA) identified hair loss profiles based on four baseline measurements: clinician-reported extent of scalp (Severity of Alopecia Tool score), eyebrow hair loss, eyelash hair loss, and patient-reported body hair loss. Logistic regression evaluated ritlecitinib (50 and 30 mg) efficacy vs placebo using Patient Global Impression of Change (PGI-C) and Patient Satisfaction with Hair Growth (P-Sat; amount, quality, and overall satisfaction) responses at Week 24, adjusting for key covariates, including latent class membership. Results: LCA identified five latent classes: (1) primarily non–alopecia totalis (AT; complete loss of scalp hair); (2) non-AT with moderate non-scalp involvement; (3) extensive scalp, eyebrow, and eyelash involvement; (4) AT with moderate non-scalp involvement; and (5) primarily alopecia universalis (complete scalp, face, and body hair loss). Adjusting for latent class membership, patients receiving ritlecitinib 30 or 50 mg were significantly more likely to achieve PGI-C response (30 mg: odds ratio, 8.62 [95% confidence interval, 4.42–18.08]; 50 mg: 12.29 [6.29–25.85]) and P-Sat quality of hair regrowth (30 mg: 6.71 [3.53–13.51]; 50 mg: 8.17 [4.30–16.46]) vs placebo at Week 24. Results were similar for P-Sat overall satisfaction and amount of hair regrowth. Conclusion: Distinct and clinically relevant hair loss profiles were identified in ALLEGRO-2b/3 participants. Ritlecitinib was efficacious compared with placebo, independent of hair loss profile at baseline. Trial registration: ClinicalTrials.gov identifier, NCT03732807. [ABSTRACT FROM AUTHOR]

Background: For children aged 6–11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. Objectives: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). Methods: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required. Results: Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response. Conclusions: Consistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6–11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit. Trial Registration: ClinicalTrials.gov Identifier NCT02612454. Plain Language Summary: Atopic dermatitis (AD) is a chronic disease that causes recurrent inflamed and rough skin rashes with itching and often soreness. In children with AD, treatment with a medication called dupilumab has shown improvements in their disease and quality of life. But most clinical trials of dupilumab in children have only lasted for 16 weeks. We investigated the effect of dupilumab in children treated for a longer time. The 321 children (aged 6–11 years) who were included in this study had taken part in a clinical trial of dupilumab because they had severe AD. They were treated with either dupilumab or a placebo (a dummy treatment) for 16 weeks. When that trial ended, they were then all treated with dupilumab for up to a year. Their average AD severity continued to get steadily better over a year of extended treatment, with almost all children reaching 50% skin improvement compared with their AD before treatment. Many children reached a point where their skin was clear or almost clear of AD for a period, and following the rules of the study they stopped taking dupilumab. In many of them, their AD slowly returned without treatment. But if they started to take dupilumab again, their AD improved, and some could even achieve skin clearance again. Over the longer term, the safety of dupilumab was similar to what was seen with short-term treatment. This study showed that children with AD aged 6–11 years benefited from receiving dupilumab for a longer period of time. [ABSTRACT FROM AUTHOR]

Introduction: Tildrakizumab (TIL), a monoclonal antibody that selectively targets interleukin-23p19, has been approved for the treatment of moderate-to-severe plaque psoriasis. According to the European Medicines Agency Summary of Product Characteristics, the recommended dose is 100 mg, but a 200 mg dose can be used in patients with certain characteristics, such as a high disease burden or body weight (BW) ≥ 90 kg. Fixed one-dose biological therapies tend to become less effective in patients with high BW. This post-hoc study describes the long-term efficacy of TIL across different BWs in pivotal clinical trials. Methods: A 5-year pooled analysis of two double-blind, randomised, controlled phase III trials—reSURFACE 1 and 2—was performed. Efficacy measures were the proportions of the patients with an absolute Psoriasis Area and Severity Index (PASI) of < 3 and < 1 and a Dermatology Life Quality Index (DLQI) of 0/1. The study population included patients randomised to TIL 100 mg or TIL 200 mg who received ≥ 1 TIL dose up to week 12 (part 1 of the trial) or up to week 28 (part 2) and patients who were responders (≥ 75% improvement in PASI) to TIL 100 or TIL 200 mg at week 28 and who were maintained on the same dose up to week 244. Efficacy was evaluated by analysing BW subgroups at weeks 28, 52 and 244. Missing data were analysed using multiple imputation. Safety was assessed in the all-patients-as-treated population. Results: The proportions of TIL-treated patients with PASI < 3 and < 1 (up to week 244) and DLQI 0/1 (up to week 52) were similar for patients with BW < 90 or ≥ 90 kg, regardless of dose. Patients ≥ 120 kg had greater efficacy outcomes at the 200 mg dose. Safety outcomes were similar regardless of treatment dose and weight (< 120/≥ 120 kg). Conclusion: In patients with BW ≥ 120 kg, TIL 200 mg is more efficacious than TIL 100 mg, with similar favourable safety profiles obtained regardless of dose and BW group. Trial registration: ClinicalTrials.gov NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). [ABSTRACT FROM AUTHOR]

Introduction: Dupilumab is the first biologic licensed to treat patients with moderate-to-severe atopic dermatitis (AD) who require systemic therapy. PROLEAD was designed to document the real-world effectiveness and safety of dupilumab in patients with moderate-to-severe AD. The present study aims to describe the baseline characteristics of patients treated with dupilumab in Germany. Methods: PROLEAD is a national, multicentre, prospective, non-interventional study, with a 2-year observation period. Adults with moderate-to-severe AD treated with dupilumab were included. Baseline characteristics, physician assessments, and patient-reported outcomes (PROs) were collected. Results: The study involved 126 sites throughout Germany. Of 839 patients assessed for eligibility, 828 were included, with baseline data available for 817 patients. Mean (standard deviation, SD) age of patients was 43.4 (15.8) years, with 396 (48.5%) patients being female. Overall, 66.6% of patients received their first diagnosis of AD during childhood. In total, 423 (51.8%) patients had co-existing atopic and type 2 inflammatory diseases, including allergic conjunctivitis (36.8%) and bronchial asthma (22.5%). Overall, 61.4% of patients had received systemic therapy, most commonly oral corticosteroids (49.9%). Approximately half of patients (51.3%) had received UV/phototherapy prior to baseline. Treatment with moderate-potent (Class 2) or potent (Class 3) topical corticosteroids was the most common concomitant treatment at baseline. However, 50.4% of patients had not received concomitant AD treatment with dupilumab at baseline. The most reported reason for initiating dupilumab was "Topical therapy alone was not sufficient" (95.1%). Mean (SD) physician assessments: EASI: 22.9 (14.5); SCORAD: 63.3 (16.2); IGA: 3.3 (0.7). Mean (SD) PROs: DLQI: 13.9 (7.1); peak pruritus NRS: 7.4 (2.3). Conclusions: Patients with moderate-to-severe AD present a long medical history, impaired quality of life, and high prevalence of co-existing type 2 inflammatory diseases. Dupilumab was used as a first-line systemic treatment in 38.6% of patients. [ABSTRACT FROM AUTHOR]

Introduction: Deucravacitinib is an oral, selective tyrosine kinase 2 inhibitor that demonstrated therapeutic benefit in a Phase 2 clinical trial of adults with moderate to severe plaque psoriasis. This analysis was designed to evaluate the effect of deucravacitinib on additional clinical and quality-of-life (QoL) outcomes and assess the relationship between these outcomes in adults with psoriasis. Methods: Post-hoc analysis of a 12-week Phase 2 trial was conducted for the three most efficacious dosage groups (3 mg twice daily, 6 mg twice daily, 12 mg once daily) and placebo. Investigator assessments for efficacy included Psoriasis Area and Severity Index (PASI), body surface area (BSA) involvement, and static Physician's Global Assessment; QoL was assessed using the Dermatology Life Quality Index (DLQI). Treatment responses and their associations were evaluated over time. Results: Deucravacitinib elicited improvement versus placebo as early as Week 4 for most efficacy measures (including changes in absolute PASI and BSA), with efficacy trends observed from Week 2 to Week 12. Improvements in QoL, assessed by achievement of a DLQI overall score of 0/1 (no effect at all on patient's life), followed a pattern similar to deucravacitinib-related clinical outcomes over 12 weeks. Overall, patients with greater improvements in psoriasis-related clinical signs and symptoms also reported greater improvement in QoL. However, complete skin clearance was not required for achieving DLQI 0/1. Conclusion: Deucravacitinib treatment produced early response and similar trends in improvements across multiple efficacy assessments and QoL in moderate to severe plaque psoriasis. Deucravacitinib has the potential to become a promising new oral therapy for this condition. Trial Registration: ClinicalTrials.gov identifier; NCT02931838. Plain Language Summary: Psoriasis is a skin disease that affects up to 2% of the population. In psoriasis, red, scaly lesions develop on the skin driven by an aberrant immune response. Psoriasis impacts not only physical and mental health but also quality of life (QoL). Deucravacitinib is being investigated as a treatment for psoriasis. We performed a Phase 2 dose-ranging, placebo-controlled, 12-week study of deucravacitinib in adults with moderate to severe psoriasis. Patients in the USA, Australia, Canada, Germany, Japan, Latvia, Mexico, and Poland participated. The study showed that oral treatment with deucravacitinib was effective using a disease severity score (percentage of patients with ≥ 75% reduction from baseline in Psoriasis Area and Severity Index score) at Week 12—placebo 7% and deucravacitinib 67%–75% for the three highest dosages—and was generally well tolerated. We further analyzed the association between efficacy and a QoL measure, the Dermatology Life Quality Index (DLQI), in patients who received placebo or the most effective dosages of deucravacitinib (≥ 3 mg twice daily). Deucravacitinib was effective at the three dosage levels tested. Skin improvement occurred early during treatment and was mirrored by improvements in DLQI score during the 12 weeks of treatment. Although some patients did not have complete clearance of their psoriasis, a large percentage of those patients still achieved considerable improvement in QoL as measured by achieving a DLQI score of 0/1 (i.e., no effect at all on the patient's QoL). [ABSTRACT FROM AUTHOR]

Introduction: Patients with plaque psoriasis often have nail psoriasis, which is difficult to treat. Ixekizumab (IXE) and ustekinumab (UST) are biologics with established efficacy in nail psoriasis. We present post hoc data from a head-to-head trial of IXE and UST (IXORA-S) to examine the efficacy in nail psoriasis in patients with moderate-to-severe plaque psoriasis over 52 weeks. Methods: In IXORA-S, randomised patients received IXE (N = 136) or UST (N = 166) per label for 52 weeks. Eighty-four (61.8%) and 105 (63.3%) of the patients treated with IXE or UST, respectively, had baseline fingernail psoriasis (Nail Psoriasis Severity Index [NAPSI] > 0); of these, 54 (64.3%) and 63 (60.0%) patients, respectively, had significant baseline fingernail psoriasis (defined as NAPSI ≥ 16 with ≥ 4 fingernails involved). The proportion of patients achieving NAPSI = 0, a NAPSI score change from baseline and correlations in Psoriasis Area of Severity Index (PASI) and NAPSI improvement over 52 weeks were examined. Results: Progressive improvement occurred in both treatment groups over 52 weeks. Statistically significantly more patients achieved NAPSI = 0 with IXE versus UST by week 16–20, and the proportions continued to increase through week 52 among patients with baseline nail psoriasis (61.9 vs. 28.6%, respectively; P < 0.001), including those with significant nail psoriasis (57.4 vs. 17.5%, respectively; P < 0.001). Similar results were observed for NAPSI score improvement from baseline to week 52. Interestingly, the presence of nail psoriasis was associated with lower skin response with UST but not with IXE. Conclusions: Ixekizumab was superior to UST in the clearance of nail psoriasis, with earlier improvement continued through 52 weeks regardless of baseline nail severity. Trial Registration: ClinicalTrials.gov identifier; NCT02561806. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare, chronic and potentially life-threatening autoinflammatory skin disease characterized by widespread eruption of sterile pustules, with or without systemic inflammation. GPP can significantly reduce patients’ quality of life (QoL). Several therapeutic approaches have been described in the literature, but there is no consensus on optimal treatment. In this review, we summarize published literature on efficacy, safety and QoL outcomes associated with current treatment of GPP with both approved and non-approved products. Embase and MEDLINE databases were searched (1980–September 2023). A search protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on the PROSPERO database (CRD42021215437). Details on publication, population, intervention, efficacy, safety and QoL were captured and checked by independent reviewers. In total, 118 publications were included, with only 19% of publications reporting on the results of clinical trials. Treatment modalities reported for GPP included non-biologic systemic therapies such as retinoids, cyclosporine and methotrexate, topical agents, biologics and small molecules, among others. Results were highly heterogeneous and methodological quality was very low, with only the interleukin-36R inhibitor spesolimab reporting results from placebo-controlled randomized trials; based on this, spesolimab is now approved for GPP treatment in regions including the USA, Japan, China, the EU and several other countries. Some other biologics are approved exclusively in Japan and Taiwan for the treatment of GPP based on open-label studies with small patient numbers in lieu of double-blind studies. Non-standardization of clinical outcomes across studies remains a major hurdle in reaching a consensus on optimal treatment. However, recently trials have been conducted using well-defined, disease-specific endpoints to evaluate GPP-targeted treatments, which will hopefully advance patient care. In conclusion, this review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the optimal treatment strategy. [ABSTRACT FROM AUTHOR]