SARS-CoV-2 infection among psoriasis patients in Germany: Data from the German registries PsoBest and CoronaBest.

BACKGROUND: Limited data exist on the characteristics of SARS-CoV-2 infections in German patients with psoriasis or psoriasis arthritis (PsA). This study analyses COVID-19 prevalence and severity of symptoms in these patients. PATIENTS AND METHODS: Participants of the German registries PsoBest and CoronaBest were surveyed in February 2022. Descriptive analyses were conducted. RESULTS: 4,818 patients were included in the analysis, mean age of 56.4 years. Positive SARS-CoV-2 tests were reported by 737 (15.3%) patients. The most frequently reported acute symptoms were fatigue (67.3%), cough (58.8%), and headache (58.3%). Longer-lasting symptoms after COVID-19 were reported by 231 of 737 patients after the acute phase. For most patients (92.9%), systemic treatment for their psoriasis or PsA was not modified during the pandemic. Patients positively tested for SARS-CoV-2 were younger on average and had more often changes in the therapy of psoriasis than negatively tested patients (8.5% vs. 5.4%). CONCLUSIONS: In this cohort of patients with psoriasis or PsA undergoing systemic treatment, SARS-CoV-2 infections were common but less frequent than in the general German population. No risk signals for more severe COVID-19 or increased infection rates were observed in the patients. In addition, systemic treatments remained largely unchanged, so that no risks can be attributed to these therapies.

Perception and Impact of COVID-19 Pandemic in Psoriasis Patients: Data from the German PsoBest and the CoronaBest Registries.

Background: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany. Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies. Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others. Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (>92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients. Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic.

Targeting IL-13 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2 years.

BACKGROUND: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)-13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2-year impacts of IL-13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate-to-severe AD. METHODS: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long-term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. RESULTS: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL-37, and S100A8) toward non-lesional expression. CONCLUSION: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non-lesional levels, further highlighting the key role of IL-13 in the pathogenesis of AD. CLINICAL TRIAL REGISTRATION: NCT03131648, NCT03587805.

Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA).

INTRODUCTION: Despite improved treatment options for plaque psoriasis within the last decades, some patients still have an inadequate response to treatment. Direct clinical evaluation between therapies used after biologic failure could facilitate physicians' choice of treatment. METHODS: COBRA (NCT04533737) was a randomized (1:1), blinded (patient and assessor), 28-week, active-comparator trial conducted in Europe from December 2020 to December 2022. The objective was to compare the efficacy and safety of brodalumab versus guselkumab in adults with moderate-to-severe plaque psoriasis and inadequate response to ustekinumab. Patients received either brodalumab 210 mg or guselkumab 100 mg. The primary [having Psoriasis Area and Severity Index (PASI)-100 response at week 16] and key secondary (time to PASI-100 response) endpoints were tested in a fixed sequence. RESULTS: Due to delays and enrollment challenges, recruitment was terminated with 113 patients enrolled of 240 planned. The proportion of patients having PASI-100 at week 16 for brodalumab was 53.4% compared with 35.9% for guselkumab [odds ratio (OR) 2.05; 95% confidence interval (CI) 0.95, 4.44; p = 0.069]. As this was not statistically significant, the hierarchical testing procedure was stopped. All other secondary PASI endpoints had nominal p-values below 0.05 in favor of brodalumab. In the time to PASI response analyses, brodalumab separated from guselkumab in estimated cumulative incidence of patients achieving a response from week 2 onward, suggesting fast onset of action with brodalumab. Quality of life measures improved in both treatment groups. The safety findings were consistent with the known safety profiles. CONCLUSIONS: Brodalumab showed a tendency toward better and earlier effect than guselkumab in patients who had failed ustekinumab. Thus, this trial provides important information in assisting physicians in their choice of therapy for patients who have failed their prior anti-interleukin (IL)-12/23 treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04533737.

Summary of Research: An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: A Multicentre, Double-Blind, Placebo-Controlled Phase 2b Study.

This is a summary of the original article "An Anti-OX40 Antibody to Treat Moderate-to-Severe Atopic Dermatitis: a Multicentre, Double-blind, Placebo-Controlled Phase 2b Study". Atopic dermatitis (AD) is an inflammatory skin disease caused by a complex interplay of genetic factors, alterations to the skin microenvironment, and immune dysregulation, including T cells that have become uncontrolled. Rocatinlimab is an investigational agent that blocks OX40, a receptor on activated T cells that has an important role in inflammatory conditions such as AD. This summary of research provides an overview of a previously published article on the results of a phase 2b study of patients with moderate-to-severe AD who were treated with different doses of rocatinlimab or placebo and followed for up to 56 weeks. Rocatinlimab significantly improved the symptoms of AD and was well tolerated. The most common adverse events were fever, nasopharyngitis, and chills. This study supports rocatinlimab as a potentially safe and effective treatment for moderate-to-severe AD.

Hidradenitis suppurativa: new insights into disease mechanisms and an evolving treatment landscape.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with a high unmet medical need. The prevalence of HS reported in most studies is 1-2%, although it is likely to be under-reported and estimates vary globally owing to variance in data collection methods, ethnicity, geographical location and under-diagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses and draining tunnels commonly affecting the axillary, anogenital, inguinal and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the tumour necrosis factor (TNF)-α and interleukin (IL)-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications; systemic therapies, including repeated and/or rotational courses of systemic antibiotics, retinoids and hormonal therapies; and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the US Food and Drug Administration and the European Medicines Agency for HS; however, its efficacy varies, with a clinical response reported in approximately 50% of patients in phase III trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have recently emerged, and agents targeting the IL-17 and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways are the most advanced in ongoing or completed phase III clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers.

Assessment of Efficacy and Safety Outcomes Beyond Week 16 in Clinical Trials of Systemic Agents Used for the Treatment of Moderate to Severe Atopic Dermatitis in Combination with Topical Corticosteroids.

Atopic dermatitis (AD) is a chronic inflammatory disease requiring efficacious and safe long-term therapy. Several new systemic treatments have recently been approved for use in patients with moderate to severe AD. However, head-to-head comparisons have not been conducted for all the currently available treatments for AD. Multiple network meta-analyses have compared efficacy of these different therapies during the initial 16-week treatment period, but not beyond week 16. Therefore, understanding the differences in key trial design and statistical methods is essential for evaluating long-term efficacy, making cross-trial comparisons, and informing treatment decisions. This focused narrative review provides an overview of data and trial methodology to guide clinicians in evaluating longer-term efficacy and safety of currently approved systemic treatments for patients with AD. We discuss important elements of longer-term trial designs and statistical analysis strategies that should be considered based on our experience as clinical trialists. In addition, a summary of key efficacy results of published, longer-term, phase III clinical trials of US Food and Drug Administration-approved, novel systemic treatments (i.e., dupilumab, tralokinumab, abrocitinib, and upadacitinib) is provided, including the design and data handling methods used. Long-term safety considerations and differences in the time-effect and safety profiles of various medications are also noted to help inform clinical decisions for individual patients. Overall, the findings of these trials support efficacy in long-term treatment with novel systemic agents for patients with AD.

Five-year Maintenance of Clinical Response and Consistent Safety Profile for Guselkumab in Asian patients with Psoriasis from VOYAGE 1 and VOYAGE 2.

INTRODUCTION: Guselkumab is a human monoclonal antibody against IL-23 used in the treatment of moderate-to-severe psoriasis. This post-hoc analysis evaluated the efficacy and safety of guselkumab in the Asian subpopulation of VOYAGE 1 and VOYAGE 2 through 5 years. METHODS: The proportions of guselkumab-treated Asian patients (VOYAGE 1 and 2) achieving Psoriasis Area and Severity Index (PASI) 90 and PASI 100, Investigator's Global Assessment (IGA) scores of 0/1 and 0, and Dermatology Life Quality Index (DLQI) scores of 0/1 (week 100 through week 252) were assessed. Non-responders were patients who met the treatment failure rules. Efficacy endpoints were analyzed using the as-observed methodology (no missing data imputation) for both studies and using non-responder imputation (for patients with any missing data) in VOYAGE 1. Safety outcomes were based on pooled data through week 252. RESULTS: Response rates through week 252 for 199 Asian patients in the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 76.8% and 80.6% (PASI 90), 26.8% and 38.7% (PASI 100), 64.3% and 87.1% (IGA 0/1), and 26.8% and 45.2% (IGA 0). DLQI (0/1) at week 252 was achieved by 52.7% of patients in VOYAGE 1 and 61.3% in VOYAGE 2, while DLQI (0) at week 252 was achieved by 32.7% of patients in VOYAGE 1 and 40.3% in VOYAGE 2. The safety profile was similar to the global population and remained consistent through 5 years. Asian patients were followed for a total of 814 patient-years (PY). Over 85% of the guselkumab-treated patients continued treatment through week 264. The rate of serious adverse events (AEs) at week 252 was 3.07/100 PY. Rates of AEs of interest were low: serious infections, 0.74/100 PY; nonmelanoma skin cancer (NMSC), no patients; malignancies other than NMSC, 0.12/100 PY; and no major adverse cardiovascular events (MACE). CONCLUSION: These analyses confirm a continuous response over 5 years, indicating that guselkumab shows therapeutic longevity in Asian patients requiring long-term treatment for moderate-to-severe psoriasis. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: VOYAGE 1 [NCT02207231] and VOYAGE 2 [NCT02207244].

Psoriasis­a long-term condition that causes a skin rash with scaly, itchy patches (plaques)­is becoming more prevalent in Asia. To control symptoms of moderate-to-severe psoriasis and achieve a strong improvement in the patient's quality of life, continuous treatment is usually needed. Guselkumab is a medicine that targets specific parts of the immune system to treat moderate-to-severe psoriasis. It is important to understand the long-term benefits of guselkumab in Asian patient populations. Our study analyzed the data from two randomized clinical trials (called VOYAGE 1 and VOYAGE 2) that studied people with moderate-to-severe plaque psoriasis. We examined results for the 199 people from Asia, including Korea and Taiwan, who took part in these studies. Overall, 162 of the 184 (86.6%) people from Asia treated with guselkumab incorporated into these studies continued the treatment for 5 years. Patients treated with guselkumab showed effective clinical responses (improvements measured by clinicians), including high skin clearance, meaning a large reduction in skin surface area affected by psoriasis. On guselkumab, patients also reported improvements in their skin-related health-related quality of life. These improvements and the efficacy of guselkumab were maintained over 5 years of follow-up. The safety results for guselkumab in the Asian subpopulation were similar to those for the global population, showing low rates of serious adverse effects, as expected from this type of medicine. Overall, our study found a favorable benefit­risk profile with continuous guselkumab treatment for 5 years in Asian people with moderate-to-severe psoriasis. This highlights that guselkumab treatment allows long-lasting control of this disease.

Open-Label Observational Study of a Topical Formulation of Calcium Spirulan Contained in a Defined Extract of the Microalga Spirulina platensis in the Treatment of Children with Molluscum Contagiosum.

Background: Molluscum contagiosum (MC) is a common viral skin infection primarily affecting children which is difficult to treat using available therapeutic approaches. The sulfated polysaccharide named calcium spirulan (Ca-SP) has demonstrated antiviral effects against herpes simplex virus in keratinocytes in vitro, and a cream containing 1.5% Ca-SP and 1% of a defined microalgae extract (Spiralin®) effectively prevented herpes labialis in a trial with susceptible individuals. This observational study aimed to show antiviral effects of a similar formulation (Spirularin® VS) against MC in children. Methods: Children with active MC lesions were treated with Spirularin® VS cream twice daily on affected skin over several months and asked to return for follow-up visits after 1 to 3 months. Clinical status of MC infection was documented at baseline and follow-up visits. Results: Of the 31 children enrolled in the study, 26 completed treatment and returned for control visits. Spirularin® VS cream was applied twice daily over a period of 1 to 9 months (mean treatment duration 3.9 months). 19/26 (73.1%) children achieved complete clearance of MC lesions with no clinical evidence of bacterial skin infection during treatment. No irritative skin reactions or unpleasant symptoms were observed or reported. Conclusion: This open-label observational study suggests that a cream formulation containing 1.5% Ca-SP and 1% Spiralin® may be an effective and safe treatment option for children with active MC lesions. The high rate of complete clearance of MC lesions and lack of adverse reactions warrant further investigation in larger, controlled trials.

Efficacy of guselkumab in difficult-to-treat psoriasis regions: Data from VOYAGE 1 and VOYAGE 2 Asian subpopulations.

Patients with psoriasis were randomized to guselkumab, placebo or adalimumab in the VOYAGE 1 and VOYAGE 2 studies. In this post hoc analysis, difficult-to-treat psoriasis regions in the Asian subpopulation for both the guselkumab and adalimumab groups were compared with placebo at week 16 and the active treatment groups were compared at week 24. Endpoints included patients achieving scores of 0 or 1 (clear or near clear) or 0 (clear) on the scalp-specific Investigator's Global Assessment (ss-IGA), Physician's Global Assessment of the hands and/or feet (hf-PGA), and fingernail PGA (f-PGA), and percentage improvement in target Nail Psoriasis Severity Index (NAPSI) score through week 24. Efficacy was also assessed by prior biologic experience at baseline. A total of 199 eligible Asian patients were included. The proportion of patients achieving "clear" or "near clear" with guselkumab was superior to adalimumab at week 24 for scalp psoriasis ss-IGA (Asian patients, 72 [85.7%] vs 35 [67.3%], P = 0.004), hands and/or feet psoriasis hf-PGA (29 [82.9%] vs 16 [61.5%], P = 0.054), and similar for fingernail psoriasis f-PGA (28 [63.6%] vs 17 [54.8%], P = 0.412). Guselkumab mean improvements in NAPSI were comparable to adalimumab (39.9% vs 35.9%, P = 0.618). Overall, the complete clearance response of scalp, and hands and/or feet at week 24 occurred in a greater proportion of patients in the guselkumab group, irrespective of baseline biologic status (treatment-naïve or treatment-experienced). Guselkumab was superior to adalimumab for the treatment of scalp, and hands and/or feet psoriasis, and proportionally higher for fingernail psoriasis. Findings were comparable to the global study population.

Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study.

BACKGROUND: Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further understanding of the abrocitinib long-term efficacy and safety profile is important for its appropriate use in treating chronic AD. OBJECTIVE: To evaluate the abrocitinib efficacy up to 48 weeks and long-term safety in patients with moderate-to-severe AD. METHODS: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis focusses on patients from the phase 3 JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) studies who completed the full treatment period of placebo or abrocitinib (200 mg or 100 mg once daily) and subsequently entered JADE EXTEND. Efficacy endpoints included the proportion of patients achieving skin clearance (Investigator's Global Assessment [IGA] 0/1 [clear/almost clear]; ≥75% improvement in Eczema Area and Severity Index [EASI-75]) and itch response (Peak Pruritus Numerical Rating Scale [PP-NRS] severity ≥4-point improvement). Safety endpoints included treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation. Data cut-off: April 22, 2020. RESULTS: As of the data cut-off, ~70% and ~45% of patients received abrocitinib for ≥36 and ≥48 weeks, respectively. Nasopharyngitis, atopic dermatitis, nausea and upper respiratory tract infections were the most frequent TEAEs. Serious TEAEs occurred in 7% and 5% and TEAEs leading to study discontinuation occurred in 9% and 7% of patients receiving abrocitinib 200 mg and 100 mg, respectively. Week 48 efficacy responses with abrocitinib 200 mg and 100 mg were as follows: IGA 0/1 52% and 39%; EASI-75 82% and 67%, and PP-NRS severity ≥4-point improvement 68% and 51%. CONCLUSIONS: In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful skin and pruritus improvement. The long-term safety profile was manageable and consistent with previous reports.

Secukinumab versus guselkumab in the complete resolution of ustekinumab-resistant psoriatic plaques: The ARROW study.

Interleukin (IL)-23-independent IL-17A production has been suggested to be involved in persistent manifestations of psoriatic disease, including anti-IL-12/23-refractory psoriatic plaques; this study aimed to test this hypothesis by investigating the clinical and molecular effects of direct IL-17A (with secukinumab) versus selective IL-23 inhibition (with guselkumab) in patients with anti-IL-12/23 (ustekinumab)-refractory psoriatic plaques. A 16-week, randomized, open-label, parallel-group, Phase IIa study (ARROW, NCT03553823) was conducted in patients with ≥1 active psoriatic plaque (total clinical score [TCS] ≥6) at screening despite treatment with ustekinumab, and a Psoriasis Area and Severity Index (PASI) score 1-10. Patients were randomized 1:1 to receive secukinumab 300 mg (n = 20) or guselkumab 100 mg (n = 20). Biopsies from one refractory ('target plaque') were obtained at baseline and Week 16. The primary endpoint was the proportion of patients whose ustekinumab-refractory target plaque achieved clear/almost clear status (TCS 0-2) at Week 16. Transcriptomic and histological analyses were conducted on target plaques to determine the molecular effects of direct IL-17A versus selective IL-23 inhibition. At Week 16, target plaque clear/almost clear status was achieved in 60.0% of patients treated with secukinumab versus 40.0% of patients treated with guselkumab (p = 0.1715). Molecular analyses identified that secukinumab modulated a greater proportion of psoriasis disease transcriptome genes (72.1% vs. 48.0%) and resulted in more histological responders (72.2% vs. 53.3%) compared with guselkumab. Secukinumab demonstrated a greater clinical and molecular effect on ustekinumab-refractory psoriatic plaques versus guselkumab. These results are consistent with the hypothesis that IL-23-independent IL-17 mechanisms may be relevant to the inflammation driving refractory manifestations of psoriasis.

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Atopic dermatitis (AD, also called atopic eczema) is a skin disease that that can affect a person for a long time and causes red or flaky skin that can be itchy and uncomfortable. Healthcare providers can prescribe medicated creams and ointments to reduce the visible signs and symptoms of AD, but these treatments are not always enough to keep it under control. A new medicine called abrocitinib is taken every day as a tablet. Abrocitinib works by slowing a part of the body's defense mechanism, called immune response, that is not functioning properly in AD. The clinical study described in this plain language summary, called JADE DARE, investigated how well and how safely 26 weeks of treatment with abrocitinib worked in adults with AD compared to an injected medicine, called dupilumab, that is also approved for AD. WHAT WERE THE RESULTS?: The study showed that abrocitinib was more effective than dupilumab in providing itch relief after 2 weeks. In addition, people who were taking abrocitinib for 4 and 16 weeks experienced greater improvement in the visible skin signs of AD than people who were taking dupilumab. The number of people who had health complaints while taking abrocitinib was similar to the number of people who had health complaints while taking dupilumab. Most of these complaints were minor. WHAT DO THE RESULTS MEAN?: Abrocitinib was more effective than dupilumab in quickly improving the signs and symptoms of moderate or severe AD in people who did not show improvement with prescribed medications like creams or ointments. Clinical Trial Registration: NCT04345367 (ClinicalTrials.gov).

Gene Expression-Based Molecular Test as Diagnostic Aid for the Differential Diagnosis of Psoriasis and Eczema in Formalin-Fixed and Paraffin-Embedded Tissue, Microbiopsies, and Tape Strips.

Highly effective targeted therapies are available to treat noncommunicable chronic inflammatory skin diseases. In contrast, the exact diagnosis of noncommunicable chronic inflammatory skin diseases is complicated by its complex pathogenesis and clinical and histological overlap. Particularly, the differential diagnosis of psoriasis and eczema can be challenging in some cases, and molecular diagnostic tools need to be developed to support a gold standard diagnosis. The aim of this work was to develop a real-time PCR-based molecular classifier to distinguish psoriasis from eczema in formalin-fixed and paraffin-embedded-fixed skin samples and to evaluate the use of minimally invasive microbiopsies and tape strips for molecular diagnosis. In this study, we present a formalin-fixed and paraffin-embedded-based molecular classifier that determines the probability for psoriasis with a sensitivity/specificity of 92%/100%, respectively, and an area under the curve of 0.97, delivering comparable results to our previous published RNAprotect-based molecular classifier. The psoriasis probability, as well as levels of NOS2 expression, positively correlated with the disease hallmarks of psoriasis and negatively with eczema hallmarks. Furthermore, minimally invasive tape strips and microbiopsies were effectively used to differentiate psoriasis from eczema. In summary, the molecular classifier offers broad usage in pathology laboratories as well as outpatient settings and can support the differential diagnosis of noncommunicable chronic inflammatory skin diseases on a molecular level using formalin-fixed and paraffin-embedded tissue, microbiopsies, and tape strips.

Matching-adjusted indirect comparison (MAIC) results confirmed by head-to-head trials: a case study in psoriasis.

BACKGROUND: Head-to-head comparisons through randomized controlled trials (RCTs) provide high-quality evidence to inform healthcare decisions. In their absence, indirect comparisons are often performed; however, evidence is limited on how valid matching-adjusted indirect comparison (MAIC)-based comparative efficacy estimates are vs. RCT-based estimates. OBJECTIVES: Compare MAIC and RCT results of guselkumab vs. secukinumab and ixekizumab to provide insight into the validity of results generated using MAIC methods. METHODS: Previously reported results from MAICs of guselkumab vs. secukinumab and ixekizumab were compared with results from ECLIPSE and IXORA-R RCTs based on risk differences between Psoriasis Area and Severity Index (PASI) 90 response rates. RESULTS: Risk difference (95% confidence interval) in PASI 90 response rates at week 48 for guselkumab vs. secukinumab was 14.4% (9.4%; 19.4%) in ECLIPSE and 9.4% (4.7%; 14.0%) in the MAIC. The risk difference at week 24 for guselkumab vs. ixekizumab was 0.0% (-5.4%; 5.4%) in IXORA-R and 0.7% (-5.1%; 6.4%) in the MAIC. CONCLUSIONS: Comparative efficacy results were consistent between MAICs and RCTs of guselkumab vs. secukinumab and ixekizumab. This analysis demonstrates that MAIC methods can provide valid relative treatment effect estimates when direct comparisons are lacking, particularly when trials with similar designs and patient populations inform the analysis.

Methods used for indirect comparisons of systemic treatments for psoriasis. A systematic review.

Background: Indirect comparisons (including network meta-analyses [NMAs]) allow us to compare benefits and risks of multiple interventions for the same clinical condition when head-to-head comparisons are not feasible. Objective: To provide guidance to the clinical community on better understanding indirect comparison methods to help them to interpret their results by applying two quality standards to published indirect comparisons of systemic biologics for moderate to severe psoriasis. Methods: A systematic literature review (SLR) of published indirect comparisons of biologics for the treatment of moderate to severe psoriasis in adults was conducted. Data extraction was performed using a predefined subset of NICE TSD7 (National Institute for Health and Care Excellence Technical Support Document 7) checklist questions and methods used to perform each analysis were descriptively compared. Methodological quality of the SLR underlying each indirect comparison was assessed using AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews version 2). Results: Twenty-two NMAs and four adjusted indirect comparisons (AICs) were identified. Although there were some similarities, for example, application of Bayesian random-effects models, several important methodological aspects varied considerably across NMAs identified, for example, classes of drugs, number of treatments and studies included, reporting and handling of different doses, and reporting of both checks for and investigations of inconsistency. Methodological comparisons across AICs were limited by the small number. The quality of most underlying SLRs described, assessed as overall level of confidence in the results, was 'critically low'. Conclusions: Understanding that there are different methodologies employed to answer differing research questions is key to helping clinicians to interpret the indirect evidence currently available in psoriasis.

Secukinumab long-term efficacy and safety in psoriasis through to year 5 of treatment: results of a randomized extension of the phase III ERASURE and FIXTURE trials.

BACKGROUND: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. METHODS: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials - ERASURE and FIXTURE - were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. RESULTS: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3-149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0-0.3) and 0.5 (0.3-0.8), respectively. CONCLUSIONS: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme.