Search

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment. Methods: Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported. Results: After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years. Conclusions: Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life. Clinical Trial Numbers: NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3). [ABSTRACT FROM AUTHOR]

Introduction: Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss and can impose a high psychosocial burden on patients. The presence of comorbid conditions may impact the management of AA in clinical practice. This analysis aims to describe disease characteristics and management of AA in patients with concomitant atopic, autoimmune, and psychiatric comorbid conditions. Methods: Data were collected from the Adelphi Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with AA conducted in France, Germany, Italy, Spain, and the UK between October 2021 and June 2022. Patients' disease severity was based on physician's definition. Physician-reported data on demographics, AA clinical characteristics, comorbid conditions, and information related to AA therapies were analyzed. Analyses were descriptive. Results: Overall, 239 dermatologists provided data for 2083 patients, of which 558 patients (27%) had at least one atopic, autoimmune, or psychiatric comorbid conditions. The most common comorbid conditions were atopic dermatitis, autoimmune thyroid disease, and anxiety. The mean (standard deviation) patient age for the three comorbidity groups was 37.6 years (12.1) and 56% of the patients were women (n = 313). In the three comorbidity groups, 51%, 50%, and 55% of patients with atopic, autoimmune, and psychiatric comorbidities had severe AA with disease progression reported as worsening in 30%, 28%, and 30%, respectively, whereas in the group with no comorbidities, 37% were described as having severe AA and 21% getting worse. Scalp hair loss was the primary sign reported across the three groups of comorbid conditions (atopic, 91%; autoimmune, 91%; psychiatric, 88%). Patients with preselected comorbidities presented more frequently AA-related signs and symptoms beyond scalp hair loss than patients without comorbid conditions. These patients were also more likely to receive topical calcineurin inhibitors, topical immunotherapy, conventional systemic immunosuppressants, and oral Janus kinase inhibitors for the treatment of their AA. Conclusion: This analysis provided insights into the burden and management of AA in patients presenting with atopic, autoimmune, and psychiatric comorbid conditions in five European countries. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to understand treatment response dynamics, including factors associated with favorable response, among patients with moderate-to-severe psoriasis who received guselkumab, adalimumab, or secukinumab. Methods: These post hoc analyses used data from the phase III clinical trials ECLIPSE and VOYAGE 1, which were conducted between September 2021 and November 2022. On the basis of absolute Psoriasis Area and Severity Index (aPASI) scores, patients were divided into short-term response types (SRT1–6, based on week 20–48 response) and long-term response types (LRT1–4, based on week 52–252 response). Response types (RTs) were based on aPASI cutoffs deemed clinically relevant by the investigators; SRT1/LRT1 were the most favorable response types. Baseline characteristics were compared across RTs, and logistic regression analyses established factors associated with SRT1/LRT1. Results: Overall, 1045, 662, and 272 patients were included in the ECLIPSE short-term, VOYAGE 1 short-term, and VOYAGE 1 long-term analyses, respectively. Mean age, body mass index (BMI), baseline aPASI score, and body surface area were lower in SRT1 than SRT6. In VOYAGE 1, adalimumab treatment, high BMI, and current/former smoking status resulted in less favorable responses. In the VOYAGE 1 long-term analysis, patients in LRT4 had the highest baseline aPASI score, were older, and were more often obese compared with other LRT groups. Regression analyses showed that SRT1 (both treatments) in VOYAGE 1 and ECLIPSE, and LRT1 (guselkumab group) in the VOYAGE 1 long-term analysis, were associated with week 16 aPASI response. In VOYAGE 1, SRT1 was associated with psoriasis duration and smoking status. Conclusions: Early treatment response and baseline characteristics, including smoking, psoriasis duration, and obesity, may be associated with longer-term response to biologics. Trial Registration Numbers: ECLIPSE: NCT03090100, VOYAGE 1: NCT02207231. [ABSTRACT FROM AUTHOR]

Treatments for alopecia areata (AA) have traditionally been prescribed off-label, and there has been no universal agreement on how to best manage the condition. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. As a better understanding of the evidence supporting the management of AA in clinical practice is needed, we conducted a systematic literature review and subsequent narrative review to describe available evidence pertaining to the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. From 2557 identified records, a total of 53 records were retained for data extraction: 9 reported data from 7 randomized controlled trials (RCTs) versus placebo, and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies. Across drug classes, data were reported heterogeneously, with little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular the JAK1/JAK2 inhibitor baricitinib. Five RCTs (three for baricitinib) demonstrated a consistent benefit of JAK inhibitor therapy over placebo across various clinical outcomes in adult patients with at least 50% scalp hair loss. Overall, hair regrowth varied widely for the other drug classes and was generally low for patients with moderate-to-severe AA. Relapses were commonly observed during treatment and upon discontinuation. Adverse effects were generally consistent with the known safety profile of each intervention. The heterogeneity observed prevented the conduct of a network meta-analysis or an indirect comparison of different treatments. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. The most robust evidence identified supported the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA. Plain Language Summary: To date, there has been no universal agreement on how to best manage alopecia areata (AA), suggesting that a better understanding of the evidence for the different treatment options is needed. Most of the treatments traditionally used for AA have not been approved for this indication. Baricitinib is the first oral selective Janus kinase (JAK) inhibitor approved for the treatment of adults with severe AA. Consequently, we extensively reviewed the available literature for evidence regarding the efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA. Although we found many potential reports, only 53 provided the type of information we believed to be relevant, with 9 describing findings from 7 randomized controlled trials versus placebo. Across treatments, there was little consistency of data collection or clinical endpoints used. The most robust evidence was for the JAK inhibitor class, in particular baricitinib, which was consistently more beneficial than placebo across various clinical outcomes in adults with at least 50% scalp hair loss. For the other classes of drugs, hair regrowth varied widely, was generally low for patients with moderate-to-severe hair loss, and commonly did not last. Reported adverse effects were generally as expected for each treatment. We found that the current management of patients with moderate-to-severe AA often relies on the use of treatments that have not been well evaluated in clinical trials. However, strong evidence supports the use of baricitinib, and other oral JAK inhibitors, in patients with severe AA. [ABSTRACT FROM AUTHOR]

Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40–60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of patients with PsA and patients with moderate-to-severe PsO. This narrative review aims to summarize nail psoriasis data generated from IXE clinical trials in patients with PsA (SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H) and/or moderate-to-severe PsO (UNCOVER-1, -2, -3, IXORA-R, IXORA-S, and IXORA-PEDS) with an emphasis on head-to-head clinical trial data. Across numerous trials explored, IXE treatment was associated with greater improvement in resolution of nail disease versus comparators at week 24, results which were maintained up to and beyond week 52. Additionally, patients experienced higher rates of resolution of nail disease versus comparators at week 24 and maintained high levels of resolution up to week 52 and beyond. In both PsA and PsO, IXE demonstrated efficacy in treating nail psoriasis, and therefore may be an effective therapy option. Trial Registration: ClinicalTrials.gov identifier UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), UNCOVER-3 (NCT01646177), IXORA-PEDS (NCT03073200), IXORA-S (NCT02561806), IXORA-R (NCT03573323), SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), SPIRIT-H2H (NCT03151551). [ABSTRACT FROM AUTHOR]

The article discusses the use of topical corticosteroids (TCS) in the treatment of inflammatory skin diseases. While TCS have been widely used and proven effective, prolonged use or application in areas with high absorption rates can lead to adverse effects such as striae formation, adrenal suppression, and Cushing syndrome. Recent studies have also associated TCS use with an increased risk of osteoporosis and fractures, particularly in women and younger individuals. The article emphasizes the need to reassess the position of TCS in treatment guidelines and consider alternative non-steroidal therapies with minimal systemic absorption. [Extracted from the article]

Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year. We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24–28 and 48–52. For the NMA at weeks 24–28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2–58.0), followed by brodalumab (37.1%; 95% CrI 17.1–62.2) and bimekizumab (30.3%; 95% CrI 12.7–53.9). For the NMA at weeks 48–52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1–93.4), followed by adalimumab (75.6%; 95% CrI 61.5–87.3) and brodalumab (71.9%; 95% CrI 38.4–93.2). Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP. [ABSTRACT FROM AUTHOR]

Five-year tildrakizumab safety data have been reported as exposure-adjusted incidence rates (EAIRs) of patients with events per 100 patient-years (PYs) of exposure. To present 5-year safety data from reSURFACE 1/2 phase 3 trials as EAIRs of events per 100 PYs of exposure, and the number needed to harm (NNH) for one adverse event of special interest (AESI) to occur. Pooled analysis from two randomized controlled trials in patients with moderate-to-severe plaque psoriasis (n = 1800). PSOLAR registry was used as safety reference data for NNH estimation. Rates of AESI with tildrakizumab were comparable with rates reported in PSOLAR. The NNH for one-year severe infection occurrence was 412 with tildrakizumab 200 mg, and negative for tildrakizumab 100 mg due to lower rates in reSURFACE trials; the NNH for malignancy was 990 for one year with tildrakizumab 100 mg (negative for tildrakizumab 200 mg); and the NNH for major adverse cardiovascular events was 355 for one year with tildrakizumab 200 mg (negative for tildrakizumab 100 mg). Tildrakizumab demonstrated a favorable safety profile over 5 years with low rates of AESI, comparable to those of the PSOLAR. Consequently, the NNH for AESI with tildrakizumab were very high or negative due to lower event rates for tildrakizumab. [ABSTRACT FROM AUTHOR]

Whether response to an interleukin (IL-17) inhibitor is different in patients with previous exposure to an IL-17 inhibitor compared with patients with exposure to biologics with other cytokine targets remains to be elucidated. Therefore, the aim of this study was to assess whether previous exposure to an IL-17A inhibitor was associated with worse response than exposure to (an)other biologic(s). All patients in the DERMBIO register treated with an IL-17A inhibitor (secukinumab or ixekizumab) were included. With an absolute Psoriasis Area and Severity Index (PASI) ≤ 2 as response, the proportion of responders treated with IL-17A inhibitors was assessed in patients previously treated with another IL-17A inhibitor and compared with patients with previous exposure to (an)other biologic(s), using a χ2 test. In total, 100, 93 and 83 patients with previous exposure to an IL-17A inhibitor and 414, 372 and 314 patients with previous exposure to (an) other biologic(s) were assessed after 3, 6 and 12 months, respectively. No differences in the proportion of patients achieving PASI ≤ 2 were observed between the 2 groups after 3 months (54% vs 57%, p = 0.59), 6 months (70% vs 66%, p = 0.42) and 12 months (69% vs 60%, p = 0.14). In conclusion, when treating patients with IL-17A inhibitors the cytokine target of the previous biologic does not appear to affect the response. [ABSTRACT FROM AUTHOR]

Background: To date, evidence on the dose adjustments of biologics in the real‐world treatment of psoriasis is limited. However, dose adjustments may have important clinical and economic implications. Aims: To study the dose adjustments of individual biologics over time in real‐world practice in Sweden. Methods: A retrospective observational study of adults with moderate to severe psoriasis was conducted based on Swedish national registry data from 2010 to 2018. Treatment episodes were identified for individual patients from the date of drug dispensation to the end of the supply of the drug. Dosing data were expressed as the proportion of treatment episodes with accumulated syringes/vials equal to, above or below the recommended guidelines. Real‐world costs were calculated and compared with costs predicted from dosing guidelines. Results: The mean dose was above recommended levels for all biologics investigated. Weighted mean dose adjustments for adalimumab, etanercept, secukinumab and ustekinumab were 13%, 23%, 8% and 3%, respectively, over the entire treatment period. Higher doses translate to higher costs, including notable increases over time vs. expected costs for secukinumab. Conclusions: Dose adjustments of biologics are frequent in clinical practice but differ for the various biologics. The mean observed increases in dose above guideline recommendations might indicate perceptions of suboptimal efficacy for biologics, with implications for the cost and cost‐effectiveness of these treatments. Further research is warranted to understand the reasons for dose adjustments in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA.Patients receiving ritlecitinib 30 mg or 50 mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48.Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23–3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28–0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05).Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.NCT03732807.Methods: Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA.Patients receiving ritlecitinib 30 mg or 50 mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48.Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23–3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28–0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05).Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.NCT03732807.Results: Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA.Patients receiving ritlecitinib 30 mg or 50 mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48.Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23–3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28–0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05).Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.NCT03732807.Conclusions: Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA.Patients receiving ritlecitinib 30 mg or 50 mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48.Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23–3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28–0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05).Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.NCT03732807.Trial Registration Number: Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA.Patients receiving ritlecitinib 30 mg or 50 mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48.Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23–3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28–0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05).Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.NCT03732807.Graphical Abstract: Patients with alopecia areata (AA) may have received several therapies for management of AA during their lives. In the ALLEGRO phase 2b/3 (NCT03732807) study, the oral JAK3/TEC family kinase inhibitor ritlecitinib demonstrated efficacy and an acceptable safety profile in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. This post hoc analysis investigated associations between prior use of AA therapies and Severity of Alopecia Tool (SALT) responses in patients receiving ritlecitinib for AA.Patients receiving ritlecitinib 30 mg or 50 mg once daily with or without an initial 4-week 200-mg daily loading dose were grouped by previous exposure to AA treatments, including topicals, intralesional corticosteroids (ILCS), topical immunotherapy, and systemic immunosuppressants or any prior AA treatment. Multivariable logistic regression analyses evaluated the association between response based on a SALT score of ≤ 20 and any prior treatment for AA at weeks 24 and 48.Of 522 patients, 360 (69.0%) had previous exposure to any AA treatment. At Week 24, SALT ≤ 20 response was positively associated with prior use of ILCS (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.23–3.65; P < 0.05) and negatively associated with prior use of systemic immunosuppressants (OR 0.50; 95% CI 0.28–0.88; P < 0.05). Prior use of topicals or topical immunotherapy was not associated with SALT ≤ 20 response at Week 24. By Week 48, no association was identified between SALT ≤ 20 response and prior use of topicals, ILCS, topical immunosuppressants, or systemic immunosuppressants (all P > 0.05). Previous exposure to any AA therapy was not associated with SALT ≤ 20 response at weeks 24 or 48 (all P > 0.05).Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.NCT03732807. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence supports the findings of an altered gut microbiota in patients with autoimmune disease. However, existing studies on the role of the gut microbiota in patients with psoriasis have demonstrated conflicting results and have mainly been based on 16s rRNA gene sequencing analysis. Objectives: To examine whether the gut microbiota of patients with psoriasis was altered in composition and functional potentials compared with healthy controls, and as a second approach compared with healthy cohabitant partners. A further aim was to investigate relationships to disease severity, and seasonal impact on the gut microbiota. Methods: In a case–control study, 126 faecal samples were collected from a sample of 53 systemically untreated patients with plaque psoriasis; 52 healthy controls matched for age, sex and body mass index; and 21 cohabitant partners. A subpopulation of 18 patients with psoriasis and 19 healthy controls continued in a longitudinal study, where four to six faecal samples were collected over 9–12 months. The gut microbiota was characterized using shotgun metagenomic sequencing analysis. Results: A significantly lower richness (P = 0·007) and difference in community composition (P = 0·01) of metagenomic species was seen in patients with psoriasis compared with healthy controls, and patients with psoriasis had a lower microbial diversity than their partners (P = 0·04). Additionally, the functional richness was decreased in patients with psoriasis compared with healthy controls (P = 0·01) and partners (P = 0·05). Increased disease severity was correlated with alterations in taxonomy and function, with a slight tendency towards a lower richness of metagenomic species, albeit not significant (P = 0·08). The seasonal analysis showed no shifts in community composition in healthy controls or in patients with psoriasis. Conclusions: The findings of a different gut microbiota in composition and functional potentials between patients with psoriasis and healthy controls support a linkage between the gut microbiota and psoriasis. These findings need to be validated in larger studies, and a potential causal relationship between the gut microbiota and psoriasis still needs to be shown. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (AD) is associated with substantial impairment in quality of life, including sleep disturbances, anxiety, and depression, which may increase the risk of cardiovascular disease (CVD). However, the association between CVD and AD is not well established. Objectives: To evaluate incidence rates (IRs) of venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE) in patients with and without AD in a population-based cohort study in Denmark, and to assess IRs of malignancies, major adverse cardiovascular events (MACE), VTE, and the distribution of Atherosclerotic Cardiovascular Disease (ASCVD) risk factors in patients with AD and rheumatoid arthritis (RA) in a nested cohort analysis. Methods: Data from all individuals aged =12 years (=18 years in the nested cohort analysis) between January 1, 2000, and December 31, 2018, were extracted from the Danish National Patient Registry. Patients with =1 AD diagnosis during the study period were matched on sex and age with 10 individuals from the general population. The nested cohort analysis included patients diagnosed with RA as an additional comparison population. In the overall cohort, IRs of VTE, DVT, and PE were assessed; the nested cohort analysis evaluated the distribution of ASCVD risk factors and incidence of malignancies, MACE, and VTE in patients with and without ASCVD risk factors (age =65 years, and history of smoking, coronary artery disease, stroke, DVT, PE, and malignancy). The follow-up period was from the first diagnosis during the study period until the occurrence of death or an endpoint, the first instance of migration, or December 31, 2018. IRs are shown per 100 patient-years (PY) of exposure with 95% confidence intervals. Results: The population-based cohort comprised 190,751 patients, including 17,341 patients with AD and 173,410 age- and sex-matched controls. The IR/100 PY of VTE was similar between the AD cohort (0.14 [95% CI, 0.12-0.16]) and the general population (0.11 [0.11-0.12]). The IR/100 PY for VTE was higher in patients with AD aged =65 years (0.71 [0.56-0.90]) than the age-matched general population (0.50 [0.46-0.54]) and lower in the younger AD cohorts (12 to <18 years, 0.02 [0.00-0.08]; 18 to <65 years, 0.12 [0.09-0.13]). The IRs/100 PY of DVT and PE were comparable between the AD cohort (DVT, 0.08 [0.06-0.09]; PE, 0.06 [0.05-0.08]) and the general population (DVT, 0.06 [0.06-0.07]; PE, 0.05 [0.05-0.05]).a The nested cohort analysis comprised 195,807 patients, including 13,432 with AD, 48,055 with RA, and 134,320 age- and sex-matched controls. Distribution of risk factors for malignancies (excluding nonmelanoma skin cancer [NMSC]), MACE, and VTE was comparable in the AD cohort and general population, but higher in patients with RA. The IR/100 PY for malignancies (excluding NMSC) was higher in patients with AD with a history of malignancy (11.41 [9.83-13.25]) than those without (0.44 [0.40-0.48]), and in those aged =65 years (3.09 [2.75-3.48]) versus <65 years (0.36 [0.33-0.40]). Similarly, the IR/100 PY for MACE was higher in patients with AD aged =65 years (2.30 [2.01- 2.63]) versus <65 years (0.15 [0.13-0.17]), and patients with a history of ASCVD (5.02 [4.37-5.76]) versus without (0.15 [0.13-0.18]). Patients with AD with a history of VTE (including DVT/PE) and inherited thrombophilia had a greater risk of VTE than patients without these risk factors. Conclusions: In these 2 large cohort studies of adults and adolescents with AD, IRs of VTE, DVT, and PE were comparable with the general Danish population. The risk of VTE, malignancy, and MACE was higher in patients with AD with a history of risk factors for ASCVD. This underscores the need for appropriate monitoring and reporting of cardiovascular events in patients with AD, and active management of risk factors with early and effective therapeutic intervention. [ABSTRACT FROM AUTHOR]

Summary: Background: Women with certain inflammatory diseases have an increased risk of giving birth to infants who are small for gestational age (SGA) or preterm birth (PTB), with maternal disease activity being the most important risk factor. However, previous studies investigating an association between psoriasis and SGA are scarce and have shown conflicting results. Aim: To investigate the association between maternal psoriasis and risk of SGA infants and PTB, respectively, both overall and stratified by psoriasis severity. Methods: This was a nationwide register‐based matched cohort study of women with psoriasis matched 1 : 10 to women without psoriasis on age at delivery, body mass index and smoking status and with their first singleton infant born during the period 2004–2017. Odds ratio (OR) and 95% CI were calculated in conditional logistic regression models adjusted for known risk factors. Results: From 516 063 deliveries, we identified 6282 women with psoriasis and 62 798 matched women without psoriasis. The risk of SGA and PTB was similar in women with psoriasis and matched controls: adjusted OR (aOR) = 1.07 (95% CI 0.98–1.17) and aOR = 1.05 (95% CI 0.93–1.19), respectively. The risk of term SGA was increased in women with psoriasis (aOR 1.11; 95% CI 1.01–1.22) compared with matched controls. Conclusion: Maternal psoriasis was not associated with increased risk of SGA or PTB. Risk of term SGA was slightly increased in women with a history of psoriasis compared with matched controls, however; these infants are likely to be constitutionally small with no increased risk of perinatal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Nail psoriasis is a chronic, difficult-to-treat condition affecting almost half of patients with psoriasis. It is associated with considerable social stigma and impairment of patients' quality of life. The aim of this study was to assess improvements in objective measures of nail psoriasis among patients from the long-term extension of the UNCOVER-3 study who received the interleukin-17A inhibitor ixekizumab and had either any degree of nail psoriasis (Nail Psoriasis Severity Index (NAPSI) >=1) or significant nail psoriasis (fingernail NAPSI ≥ 16 and ≥ 4 fingernails involved) at baseline. Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. At week 60, a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, an effect which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis through 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline. [ABSTRACT FROM AUTHOR]

In addition, the patient achieved a 10% weight loss, which may have contributed to the reduction of disease burden.1 Roflumilast could represent a novel and convenient treatment option for all severity stages of HS as well as associated comorbidities. GLO:F03/01nov22:bjd21744-toc-0001.jpg PHOTO (COLOR): . gl Hidradenitis suppurativa (HS) is a chronic, inflammatory disease characterized by recurrent nodules, tunnels and excessive scarring in predominately inverse body regions.1 Moderate-to-severe HS is associated with various comorbidities, for example overweight and chronic obstructive pulmonary disease (COPD).2 Currently, adalimumab is the only biologic drug approved for HS by the European Medicines Agency.3 However, the drug survival time of adalimumab and other off-label biologics appears to be limited in HS.4 Therefore, alternative treatments are highly needed. Furthermore, experimental studies have found roflumilast to be up to 90 times more potent in inhibiting PDE4 isoforms compared with apremilast.8 In contrast to biologic therapy, oral roflumilast treatment does not require routine laboratory monitoring, and with proven efficacy in COPD and weight loss commonly reported during treatment, roflumilast may also work directly on associated HS comorbidities.5 In the present case, we observed considerable improvements in clinical HS presentation and quality-of-life measures with oral roflumilast therapy. [Extracted from the article]

Zerovalent niobium, Nb(0), and tantalum, Ta(0), nanoparticles are prepared via a one-pot, liquid-phase synthesis. For this, NbCl5/TaCl5 are dissolved in pyridine and reduced by lithium pyridinyl. Deep black suspensions of very small, highly uniform nanoparticles are obtained with average diameters of 2.1 ± 0.4 nm (Nb(0)) and 1.9 ± 0.4 nm (Ta(0)). Whereas suspensions are chemically and colloidally stable, powder samples are very reactive. TEM/HRTEM, XRD, FT-IR, and XANES are used for characterization. [ABSTRACT FROM AUTHOR]

Introduction: A number of treatments for atopic dermatitis (AD) are available; however, long-term treatment patterns and healthcare consumption in patients with AD are poorly described. Methods: We conducted a registry-based longitudinal drug utilization study among Danish patients with AD that were referred to their first-ever visit at hospital-based dermatology clinics. Their first visit was in the period between 1 January 2005 and 31 December 2012, and patients were followed up to 5 years after their first visit. Results: In total, 8213 people with a first-time hospital dermatologist contact for AD were included in the study (3514 aged 0–9 years, 1501 aged 10–19 years, 3198 aged 20 years or older). At first visit, a baseline history of moderately potent topical corticosteroid (TCS) use was seen among 46.6% of children (0–9 years), whereas potent or very potent TCS use was more frequently among older individuals (e.g., 51.1% and 25.6% of people aged 50 years or older had used potent and very potent TCS, respectively). The median (interquartile range) annual number of visits to general practitioners was 4 (2–7) for children and 5 (2–8) for adults, in the 12 months prior to referral. Three years after referral, these numbers had decreased to 2 (1–4) and 3 (1–6), respectively. In the first year after referral, 6% of patients were prescribed systemic corticosteroids, whereas other systemic therapies were used in 5% or less. Conclusions: After referral, low proportions of patients received systemic treatment, or potent TCS. These findings highlight considerable differences in treatment patterns between general practitioners and private practice dermatologists, compared with hospital-based dermatologists, and emphasize the need for better adherence to evidence-based treatment guidelines. [ABSTRACT FROM AUTHOR]

We examined the incidence and risk of cancer in all patients treated with omalizumab in Denmark for CU and asthma. The study cohort comprised a total of 1444 participants treated with omalizumab (998 women, 446 men) with a mean (SD) age of 40-6 years (± 16-1) of which 1009 (69-9%) had CU, 370 (25-6%) had asthma, and 65 (4-5%) had CU and asthma. The unexposed age- and sex-matched control group consisted of 14 397 participants (9961 women, 4436 men) with a mean age of 40-5 years (± 16-0) of which 2891 (20-1%) had CU, 11 430 (79-4%) had asthma, and 76 (0-5%) had CU and asthma. [Extracted from the article]

TiN and ZnSiN2 nanoparticles are obtained via a novel pyridine‐based synthesis route. This one‐pot liquid‐phase route strictly avoids all oxygen sources (including starting materials, surface functionalization, solvents), which is highly relevant in regard of the material purity and material properties. Colloidally stable suspensions of crystalline, small‐sized TiN (5.4±0.4 nm) and ZnSiN2 (5.2±1.1 nm) are instantaneously available from the liquid phase. Elemental analysis and electron energy loss spectroscopy confirm the purity of the compounds and specifically the absence of oxygen. The as‐prepared ZnSiN2 show yellowish emission (500‐700 nm) already at room temperature with its maximum at 570 nm. [ABSTRACT FROM AUTHOR]

Nine Ge−Fe carbonyl cluster compounds are prepared via ionic liquids‐based synthesis. This includes the novel compounds [EMIm][Fe(CO)3I(GeI3)], [EHIm][Fe(CO)3I(GeI3)], [BMIm][GeI2{Fe(CO)4}2(μ‐I)][AlCl4]2, [GeI2{Fe(CO)4}2(μ‐I)][Fe(AlBr4)3], [BMIm]2[(FeI2)0.75{Fe(CO)2I(GeI3)2}2], and [EHIm][Fe(CO)4(GeI2)2Fe(CO)3GeI3] as well as the previously reported compounds (Fe(CO)4(GeI3)2, FeI4{GeI3Fe(CO)3}2, and Ge12{Fe(CO)3}8(μ‐I)4 (EMIm: 1‐ethyl‐3‐methylimidazolium, EHIm: 1‐ethylimidazolium, BMIm: 1‐butyl‐3‐methylimidazolium). With this series of compounds, a comparison of synthesis conditions and structural features is possible and, for instance, allows correlating the composition and structure of the respective Ge−Fe carbonyl cluster compounds with the type and acidity of the ionic liquid. With [EMIm][{GeI3}2Fe(CO)3I], moreover, we can exemplarily show the thermal decomposition as a single‐source precursor in the ionic liquid, resulting in bimetallic Ge−Fe nanoparticles with small size and narrow size distribution (7.0±1.4 nm). [ABSTRACT FROM AUTHOR]

Early response to treatment with biologics might be important for the stability of psoriasis and long-term outcome. The aim of this study was therefore to assess whether risk of flares and drug survival are associated with disease activity in the first 6 months of treatment of psoriasis with biologics. Biologic-naïve patients from the Danish nationwide registry, DERMBIO, were grouped based on absolute Psoriasis Area and Severity Index (PASI) during the first 6 months of treatment, as: PASI = 0, PASI > 0-≤2, PASI > 2-≤ 4, and PASI > 4. Among 1,684 patients, 746 achieved PASI= 0, 485 PASI > 0-≤2, 246 PASI > 2-≤4, and 207 PASI > 4. Longer flare-free period and drug survival were observed for patients with lower PASI in the first 6 months of treatment (adjusted hazard ratios for flares (95% confidence interval) with PASI= 0 as reference: PASI > 0-≤2 (1.35 (1.11-1.72]), PASI > 2-≤ 4 (2.32 [1.80-2.99]), and PASI > 4 (2.38 [1.80-3.15])). In conclusion, a low PASI in the first 6 months of treatment with biologics in biologic-naïve patients with psoriasis was associated with a more stable disease course, lower risk of flares, and longer drug survival. [ABSTRACT FROM AUTHOR]

The initiation and evaluation of treatment with biologics for psoriasis is based on the Psoriasis Area Severity Index (PASI) and/or Dermatological Life Quality Index (DLQI). However, these indices do not always correlate well, and changes in the DLQI do not always follow changes in the PASI. Based on data from the Danish national registry (DERMBIO), this study investigated the correlation between changes in PASI and DLQI in a cohort of patients with moderate-to-severe psoriasis treated with biologics or apremilast using Spearman's rank correlation analyses. The correlation analysis of 1,677 patients, of whom 276 had available data after 5 years, showed weak-to-moderate correlation between PASI and DLQI during a 5-year period and between changes in PASI and DLQI: 0.58 (p < 0.0001) for baseline to 3 months and 0.42 (p < 0.0001) for 3 to 12 months. The first question on "Symptoms and feelings"made up the largest proportion of the overall DLQI. The correlation between PASI and DLQI is weakto- moderate and varies over time. Changes in PASI correlate weak-to-moderately with changes in DLQI during the first 12 months of treatment, with symptoms being the most important factor contributing to impaired quality of life. [ABSTRACT FROM AUTHOR]

Objectives To assess the effectiveness and tolerability of first- and second-line interleukin (IL)-17A inhibitor treatment in PsA patients from 2014 to 2021 using data from the Danish Rheumatology Registry (DANBIO) by investigating adherence to therapy. Method PsA patients recorded in the DANBIO who received a first- or second-line IL-17A inhibitor treatment were included in this study. All patients included had previously received one or more TNF inhibitor treatment. Baseline characteristics were analysed in subgroups as first-line IL-17A inhibitor treatment and second-line IL-17A inhibitor treatment. Adherence to therapy of first- or second-line IL-17A inhibitor treatments was reported as Kaplan–Meier plots. Results A total of 534 patients were included in the study, with 534 first-line switchers (secukinumab: 510, ixekizumab: 24) and 102 second-line switchers (secukinumab: 35, ixekizumab: 67). Baseline characteristics showed a similar HAQ and visual analogue scale (VAS) for pain. VAS global, 28-joint DAS with CRP and the previous number of biologic DMARD treatments were similar, with a greater value for second-line switchers. First-line ixekizumab-treated patients present a younger age, greater percentage of females, a lower disease duration and a lower CRP value. Concomitant MTX use was greater for the first-line secukinumab-treated patients. First- and second-line switchers had a similar adherence to therapy. Second-line secukinumab and second-line ixekizumab switchers showed a similar adherence to treatment. Conclusion PsA patients receiving first- or second-line IL-17A inhibitors showed homogeneous baseline characteristics and similar adherence to therapy. Treatment failure of the first IL-17A inhibitor treatment should not preclude a second-line IL-17A inhibitor treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE Topical corticosteroids (CSs) are commonly used to treat inflammatory skin conditions including eczema and psoriasis. Although topical CS package inserts describe hyperglycemia and glycosuria as adverse drug reactions, it is unclear whether topical CS use in real life is also associated with an increased risk of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Two matched case-control studies and one cohort study were conducted using routinely collected health care data from Denmark and the U.K. A total of 115,218 and 54,944 adults were identified as case subjects with new-onset T2D in the Danish and U.K. case-control study, respectively. For the Danish cohort study, 2,689,473 adults were included. The main exposure was topical CSs, and the outcome was incident T2D. RESULTS Topical CS was significantly associated with T2D in the Danish (adjusted odds ratio [OR] 1.25 [95% CI 1.23–1.28]) and U.K. (adjusted OR 1.27 [95% CI 1.23–1.31]) case-control studies. Individuals who were exposed to topical CSs had significantly increased risk of incident T2D (adjusted hazard ratio 1.27 [95% CI 1.26–1.29]). We observed significant dose-response relationships between T2D and increasing potency of topical CSs in the two Danish studies. The results were consistent across all sensitivity analyses. CONCLUSIONS We found a positive association between topical CS prescribing and incident T2D in Danish and U.K. adult populations. Clinicians should be cognizant of possible diabetogenic effects of potent topical CSs. [ABSTRACT FROM AUTHOR]

This article discusses the importance of considering patients' perspectives in the treatment of psoriasis, a chronic skin disease that can significantly impact quality of life. The study conducted a Delphi consensus involving psoriasis patients, physicians, and nurses to determine the definition of freedom from disease in psoriasis. The results showed that while there was a high level of consensus among all groups, there were some differences in the perceived importance of various aspects of freedom from disease. For example, physicians placed greater importance on the management of clinical symptoms, while patients were more concerned about the cost of treatments. The study also found that patients with milder psoriasis placed greater importance on psychosocial elements and healthcare team support, while patients with more severe psoriasis were less concerned with the cost of treatment. Additionally, females placed greater importance on psychosocial elements, such as worrying about other people's reactions to their skin. The findings suggest the need for personalized treatment plans and shared decision-making between patients and healthcare professionals. However, it is important to note that the study has limitations, such as the potential lack of representativeness in certain groups. [Extracted from the article]

CoN, Ni3N and Cu3N nanoparticles were obtained by pyridine-based synthesis using CoI2, NiI2, and CuI as the starting materials as well as NH3/KNH2 as the base and nitride source. Colloidally stable suspensions of crystalline, small-sized CoN (4.5 ± 0.7 nm), Ni3N (2.7 ± 0.4 nm), and Cu3N (4.2 ± 0.7 nm) were instantaneously available from refluxing pyridine. This approach strictly avoids all oxygen sources (including starting materials and solvents), which is highly relevant with regard to the material purity and properties. [ABSTRACT FROM AUTHOR]

It is unclear whether psoriasis is a progressive disease that requires early aggressive intervention. This population-based study identified patients with psoriasis and psoriatic arthritis (PsA). Survival analysis and Kaplan--Meier life table techniques were used. The study comprised 10,011 psoriasis patients (severe n = 4,618), and 1,269 patients also had PsA. Incidence of PsA increased with duration of cutaneous symptoms (p = 0.0001). Psoriasis diagnosed before age 20 or 30 years, respectively, suggested a lower risk of PsA than psoriasis diagnosed after age 50 years, yet age at first cutaneous symptoms did not predict development of PsA. No clear association with disease severity was found. PsA incidence appeared stable with longer duration of psoriasis, but further data are needed to firmly establish the relationship with age of psoriasis onset. [ABSTRACT FROM AUTHOR]

Monitoring of biological treatment efficacy for psoriasis is based on clinical evaluation and patient's quality of life. However, long-term correlation between Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) in real life has not been studied in patients treated with ustekinumab. All patients with psoriasis treated with ustekinumab at our department were included (n = 120) in this study. Correlation analyses between the change in PASI and DLQI and the individual subquestions in DLQI were performed using Spearman's rank correlation coefficient. A correlation value of 0.57 (p-value < 0.001) and 0.45 (p-value < 0.001) between PASI and DLQI were found in the period baseline months and baseline 12 months, respectively. In DLQI subquestions, the greatest association was found for the questions on "Symptoms and feelings". Objective improvements in the severity of psoriasis were weakly to moderately associated with improvements in quality of life in patients with psoriasis treated with ustekinumab. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune-mediated inflammatory disease, which, in studies among adults, have been shown to cluster with autoimmune disease. The aim of this cross-sectional register study was to examine possible associations between 9 pre-selected autoimmune diseases and psoriasis in children and adolescents. The study population consisted of all individuals living in Denmark, age under 18 years on 31 December 2012. A total of 1,925 children and adolescents with psoriasis and 1,194,712 without psoriasis were identified. Psoriatic arthritis (adjusted odds ratio (OR) 10.08; 7.97-12.74), rheumatoid arthritis (adjusted OR 6.61; 2.75-15.87) and vitiligo (adjusted OR 4.76; 1.71-13.20) showed strong associations with psoriasis. In addition to increased risk of selected autoimmune diseases, the presence of psoriasis was associated with increased risk of multiple concurrent autoimmune diseases compared with children and adolescents without psoriasis. Clinicians should be aware of extracutaneous symptoms when treating children and adolescents with psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis is a common, chronic inflammatory skin disease associated with a large number of comorbidities. Though management of moderate-to-severe plaque psoriasis has greatly improved in recent years, patients with refractory disease or contraindications to available treatments still constitute therapeutic challenges. Oral roflumilast, a selective phosphodiesterase-4 (PDE-4) inhibitor, is approved for chronic obstructive pulmonary disease. Experimental studies have shown increased PDE-4 activity in psoriatic skin, and inhibition results in down-regulation of key inflammatory cytokines. Based on mode-of-action and available literature, we hypothesize that oral roflumilast is a future treatment for plaque psoriasis. Contrary to most existing psoriasis therapies, roflumilast has a favorable safety profile and holds the potential to improve not only skin manifestations but also commonly seen comorbidities. If efficacy and safety are confirmed in randomized settings, roflumilast can fill in a large unmet need and may represent a novel, relatively inexpensive, and convenient therapy positioned before biologics. [ABSTRACT FROM AUTHOR]

Bimetallic NiIr4 and NiOs4 alloy nanoparticles are prepared and studied with regard to their performance in catalytic hydrogenation reactions. NiIr4 and NiOs4 nanoparticles are obtained by oleylamine-driven reduction and exhibit mean diameters of (8.9±1.3) and (6.8±1.4) nm at low agglomeration. The phase composition was determined in detail by using different methods, which include high-resolution TEM, scanning transmission electron microscopy, selected-area electron diffraction, X-ray diffraction, and energy-dispersive X-ray spectroscopy. This and results in a uniform distribution of both metals Ni-Ir and Ni-Os with a ratio of 1:4. The catalytic performance of the NiIr4 and NiOs4 nanoparticles for hydrogenation reactions is evaluated using three selected model substrates: 1-octene, cinnamaldehyde, and diphenylacetylene. Similar sized Ni, Ir, and Os nanoparticles were used as references. Most remarkable are the excellent selectivity of NiOs4 in the hydrogenation of cinnamaldehyde and the promising formation of ( Z)-stilbene in terms of conversion activity and selectivity. The alloying of Ir and Os with Ni, moreover, is highly cost efficient. In general, both bimetallic alloy nanoparticles, NiIr4 and NiOs4, are shown here for the first time in terms of synthesis, composition, and catalytic hydrogenation. [ABSTRACT FROM AUTHOR]

Psoriasis has been associated with increased risk of myocardial infarction (MI) in some, but not all, studies. This study investigated the risk of MI in patients with psoriasis and psoriatic arthritis in Denmark. All residents aged =18 years from 1 January 2008 through 31 December 2012 were included. Adjusted hazard ratios (HRs) did not show an increased risk of MI in patients with mild psoriasis (HR 1.02; 95% confidence interval (95% CI) 0.96-1.09), whereas the risk was slightly increased in patients with severe psoriasis (HR 1.21; 1.07-1.37). Stratified by age, there was no increased risk of MI in any specific age group, regardless of severity. Limited to first-time MI, the risk was increased only in patients with severe psoriasis aged <50 years (HR 1.52; 1.03-2.25). The same applied to patients without psoriatic arthritis (severe psoriasis aged <50 years; HR 1.74; 1.11-2.72). In analyses restricted to patients with psoriatic arthritis, age-specific strata did not show any association between psoriatic arthritis and MI risk. [ABSTRACT FROM AUTHOR]

The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012 were examined. There was a female predominance ranging between 50.0% (2007) and 55.4% (2009), and the mean age at time of diagnosis was 47.7-58.7 years. A total of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak incidence of 199.5 in 2010. Incidence rates were higher for women, and patients aged 60-69 years, respectively. Use of systemic non-biologic agents, i.e. methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA) increased over the study course, and were used in 15.0% of all patients. Biologic agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were utilized in 2.7% of patients. On a national level, incidence of psoriasis fluctuated during the 10- year study course. The relationship between psoriasis incidence and age appeared to be relatively linear, and disease prevalence was comparable to that in other European countries. [ABSTRACT FROM AUTHOR]

Adult atopic dermatitis (AD) is associated with overweight, obesity and cardiovascular diseases (CVD) in Americans, similarly to psoriasis, but no increased risk of CVD has been shown in European patients with AD. This study investigated the prevalence and risk of gallstones in adults with AD and in those with psoriasis as a proxy for obesity using nationwide data for all Danish citizens ≥ 30 years of age. Outcome was a diagnosis of gallstones. Odds ratios (ORs) were calculated by logistic regression (cross-sectional study) and hazard ratios (HRs) were estimated by Cox regression (cohort study). The study comprised 6,742 patients with AD, 53,810 patients with psoriasis, and 3,534,164 general population subjects. The prevalence of gallstones was 3.8%, 3.5% and 5.0% in the general population, AD and psoriasis patients, respectively. Adjusted ORs were 0.81 (0.71-0.92) for AD and 1.18 (1.14-1.23) for psoriasis. During follow-up, adjusted HRs were 0.72 (0.56-0.90) for AD and 1.10 (1.02-1.18) for psoriasis. The findings highlight important differences in obesity and lifestyle factors among patients with AD and those with psoriasis. [ABSTRACT FROM AUTHOR]

Introduction Patients with psoriasis have increased risk of cardiovascular disease, but data on atopic dermatitis (AD) are less clear-cut. However, it is well-established that erectile dysfunction (ED) can serve as a risk marker for coronary disease. Aim To investigate the incidence, prevalence, and risk of ED in men with psoriasis and AD. Methods The sample included all Danish men at least 30 years old. In patients with AD and psoriasis, we determined disease severity based on use of systemic therapy. We performed a cross-sectional study (January 1, 2008) using logistic regression to estimate the prevalence and odds ratio of ED. Moreover, in a cohort study design, patients were followed from January 1, 2008 through December 31, 2012, and Cox regression models were used to estimate adjusted hazard ratios of new-onset ED. Models were adjusted for potential confounding factors, including age, socioeconomic status, health care consumption, smoking, alcohol abuse, diabetes, and cholesterol-lowering drug use. Main Outcome Measures The outcome was initiation of pharmacotherapy used for treatment of ED. Results The sample consisted of 1,756,679 Danish men (age range = 30–100 years), of which 2,373 and 26,536 had adult AD (mild = 1,072; severe = 1,301) and psoriasis (mild = 21,775; severe = 4,761), respectively. Mean ages (SDs) were 53.0 (14.6), 46.7 (12.0), and 56.3 (13.8) years for the general population, patients with AD, and patients with psoriasis, respectively. Prevalences of ED were 8.7%, 6.7%, and 12.8% for the general population, patients with AD, and patients with psoriasis, respectively. Adjusted odds ratios (logistic regression) of ED were decreased in patients with AD (0.68; 0.57–0.80) but increased in those with psoriasis (1.15; 1.11–1.20). Adjusted odds ratios for mild and severe AD were 0.63 (0.48–0.82) and 0.72 (0.58–0.88), respectively, and those for psoriasis these were 1.16 (1.11–1.21) and 1.13 (1.03–1.23). Adjusted hazard ratios (Cox regression) were 0.92 (0.76–1.11) for AD and 1.14 (1.08–1.20) for psoriasis. The ED risk was not increased in men with mild AD (0.85; 0.63–1.14) or severe AD (0.97; 0.76–1.24) but was significantly increased in men with mild psoriasis (1.13; 1.09–1.20) and severe psoriasis (1.17; 1.04–1.32). Conclusion We found an increased prevalence and risk of ED in men with psoriasis, whereas the risk was comparable to (and even slightly lower than) the general population for men with AD. Egeberg A, Hansen PR, Gislason GH, et al. Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis. J Sex Med 2017;14:380–386. [ABSTRACT FROM AUTHOR]

Background: Emerging data suggest that rosacea is associated with several comorbidities; however, the causes of mortality in patients with rosacea have not yet been investigated. Objective: We evaluated all-cause and cause-specific death rates in patients with rosacea in a population-based Danish cohort study. Methods: All Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2012 with rosacea diagnosed by hospital dermatologists were linked in nationwide registers and compared with age- and sex-matched general-population subjects (1:5 ratio). Death rates were calculated per 1000 person-years, and hazard ratios (HRs) were estimated using Cox regression models. Results: The total cohort ( n = 35,958) included 5993 patients with rosacea and 29,965 age- and sex-matched individuals from the general population. During the maximum 15 years of follow-up, 664 (11.1 %) patients with rosacea and 3121 (10.4 %) patients in the reference population died. The risk of all-cause mortality was similar in patients with rosacea and the reference population [HR 1.06, 95 % confidence interval (CI) 0.98-1.15]. Analyses of cause-specific mortality revealed a significantly increased risk of death due to gastrointestinal diseases in patients with rosacea (HR 1.95, 95 % CI 1.31-2.89), primarily related to hepatic disease. No increased risk of death due to other major disease categories, e.g. cancer, cardiovascular, neurological, or infectious diseases was observed. Conclusion: We observed a significantly increased risk of death due to gastrointestinal diseases (primarily hepatic disease) in patients with rosacea; however, we found no increased risk of death due to other causes such as cardiovascular or neurological diseases. Although this does not necessarily imply a causal link, the findings underscore the association between rosacea and gastrointestinal disease, but also that rosacea may be associated with increased risk factors, including alcohol consumption. [ABSTRACT FROM AUTHOR]

Erythrodermic psoriasis (EP) and erythroderma exfoliativa (EE) are acute and potentially life-threatening inflammatory reactions. We estimated hazard ratios (HRs) of 3-year mortality following hospitalization for EP or EE compared with general population controls, patients hospitalized for psoriasis vulgaris, and toxic epidermal necrolysis (TEN), respectively. We identified 26 and 48 patients with a first-time hospitalization (1997-2010) for EP and EE, respectively (10 matched populationcontrols for each patient), 1,998 patients with psoriasis vulgaris, and 60 patients with TEN. During follow-up, 8 (30.8%) patients with EP, 19 (39.6%) patients with EE, and 34 (56.7%) patients with TEN died. Compared with population-controls, adjusted HRs were 4.40 (95% CI 1.66-11.70) for EP and 2.16 (1.21-3.82) for EE. Compared with psoriasis vulgaris, adjusted HRs were 1.83 (0.90-3.73) for EP, and 1.28 (1.01-1.63) for EE. The risk was significantly lower in EP (0.38 (0.16-0.91)) and in EE (0.50 (0.36-0.71)), compared with TEN. Mortality in EP and EE is high, and close follow-up is advised. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis ( AD) is a chronic inflammatory skin condition with a multifactorial etiopathogenesis. Studies have suggested that several perinatal factors may influence the risk of AD in early childhood. We investigated possible neonatal risk factors such as jaundice, blue light phototherapy, birthweight, gestational age at birth, and season of birth on the risk of developing AD in the first 5 years of life. Materials & Methods Data were collected through Danish nationwide administrative registers. All newborn children between 1997 and 2007 (n = 673,614) were included in the cohort. Incidence rate ratios ( IRRs) were estimated with 95% confidence intervals (95% CIs) by multivariate Poisson regression analyses. Results We identified a total of 85,743 children with AD in the first 5 years of life. The risk of AD was slightly increased in children with neonatal jaundice ( IRR 1.13 [95% CI 1.06-1.21]). Preterm birth was inversely associated with the risk of AD ( IRR 0.74, [95% CI 0.68-0.81]) as well as low birthweight ( IRR 0.68, [95% CI 0.61-0.75]). Children born in fall and winter seasons had an increased risk of AD compared to spring and summer. No association between neonatal blue light therapy and the risk of AD was found. Conclusions Low birthweight and preterm birth were inversely associated with AD, while neonatal jaundice and cold seasons of birth were associated with an increased risk of AD. [ABSTRACT FROM AUTHOR]

Objective: Rosacea is a common chronic inflammatory skin disorder where upregulation of matrix metalloproteinases (MMPs) and antimicrobial peptides (AMPs) is observed. Notably, inflammation, MMPs, and AMPs are also involved in the etiopathogenesis of neurodegenerative disorders including certain forms of dementia such as Alzheimer disease (AD). Based on several clinical observations, we investigated the association between rosacea and dementia, including AD in Danish registers.Methods: All Danish citizens aged ≥18 years between January 1, 1997 and December 31, 2012 were linked at the individual level through administrative registers. Cox regression was used to calculate unadjusted and adjusted hazard ratios (HRs).Results: The study comprised a total of 5,591,718 individuals, including 82,439 patients with rosacea. A total of 99,040 individuals developed dementia (any form) in the study period, of whom 29,193 were diagnosed with AD. The adjusted HRs of dementia and AD were 1.07 (95% confidence interval [CI] = 1.01-1.14), and 1.25 (95% CI = 1.14-1.37), respectively, in patients with rosacea. Stratified by sex, the HRs of AD were 1.28 (95% CI = 1.15-1.45) and 1.16 (95% CI = 1.00-1.35) in women and men, respectively. When results were stratified by age at study entry, the risk of AD was only significantly increased in individuals ≥60 years old (adjusted HR = 1.20, 95% CI = 1.08-1.32). When analyses were limited to patients with a hospital dermatologist diagnosis of rosacea only, the adjusted HRs of dementia and AD were 1.42 (95% CI = 1.17-1.72) and 1.92 (95% CI = 1.44-2.58), respectively.Interpretation: Rosacea is significantly associated with dementia, particularly AD. Increased focus on symptoms of cognitive dysfunction in older patients with rosacea may be relevant. Ann Neurol 2016;79:921-928. [ABSTRACT FROM AUTHOR]

Psoriasis is associated with depression, myocardial infarction (MI) and stroke. Patients with depression have increased cardiovascular risk. However, the link between psoriasis, depression and cardiovascular disease is unclear. This link was investigated in a nationwide Danish cohort of patients with psoriasis (n = 29,406). Incidence rates were calculated, and incidence rate ratios (IRRs) adjusted for age, gender, socio-economic status, medication and comorbidity were estimated by Poisson regression models. Risk of MI (IRR 1.57, 95% confidence interval (95% CI) 1.07-2.29), stroke (IRR 1.95, 95% CI 1.43-2.66), and cardiovascular death (IRR 2.24, 95% CI 1.53-3.26) were increased significantly during acute depression, and risk of stroke (IRR 1.51, 95% CI 1.19-1.90) was increased significantly in chronic depression. During remission from depression, only the risk of stroke was increased. In conclusion, in patients with psoriasis, depression is associated with increased risk of MI, stroke and cardiovascular death, especially during acute depression. [ABSTRACT FROM AUTHOR]

The article discusses research which showed the prevalence of cancer in adult patients with atopic dermatitis (AD), a common chronic inflammatory skin disease. Topics discussed include the potential explanatory factors for altered risk in AD, association between AD and non-melanoma skin cancer (NMSC) and cervical cancer and systemic anti-inflammatory agents associated with an increased risk of NMSC.

The article presents a study regarding the prevalence of psoriasis as a chronic systemic inflammatory skin disease. It examines the high risk of autoimmune hepatitis in persons with psoriasis. It also cites the prevalence of autoimmune disease in children of patients with an autoimmune diseases and psoriases.

For many patients including those with psoriasis, scientific manuscripts comprising clinical outcomes including psoriasis area severity index (PASI) and/or physician global assessment (PGA) may be difficult to understand. However, most patients can relate to images at baseline and follow-up, particularly for dermatological diseases. This study aimed to assess the proportion of shared clinical images in psoriasis trials. A systematic review adhering to the PRISMA guidelines was performed. The review was limited to randomized controlled trials, and among these, only investigations involving biological agents for treatment of psoriasis were included. The Embase, MEDLINE and Scopus databases were searched for eligible studies published from inception to October 26, 2021. In total, 152 studies were included. When combining these, 62,871 patients were randomized. Overall, 203 images were shared depicting 60 patients in the manuscripts yielding an overall sharing rate of 0.1%. Patient images are seldom incorporated in clinical trial manuscripts which impairs interpretation for patients. Inclusion of image material would strengthen the patients' perspective and understanding on what treatment effects that can be expected. As such, this systematic review should be an invitation to the pharmaceutical industry, other sponsors, and editorial offices to improve easy transfer of information to patients using image data. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course.Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course.Kaplan–Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann–Whitney U and chi‐squared tests compared patients who started biologics early with those who began biologics later in the disease course.Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well‐being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0–51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0–32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0–53.2) and 45.0 (36.0–55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04).Age at diagnosis, general well‐being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion It is unknown whether the pre‐biologic treatment journey affects subsequent biologic drug survival.To examine the potential impact of a complex treatment journey on subsequent biologic drug survival in patients with psoriasis.The study utilized longitudinal data from Danish national registries and included all patients who, for the first time, initiated a biological treatment for psoriasis. Maximum follow‐up was 5 years and patients were included from 1 January 2010 to 30 June 2021. The study used three definitions of exposure to a complex treatment journey and the following conventional systemic treatments: acitretin, cyclosporine, dimethyl fumarate and methotrexate. The first definition was the cumulative number of treatment series. The second definition comprised the number of unique treatments. The third definition was time from the first conventional systemic treatment to biological therapy. Drug survival for the three definitions were illustrated using Kaplan–Meier curves and compared using log‐rank test. The sensitivity analysis largely confirmed these findings by grouping patients according to pharmacotherapy.A total of 2496 patients were included in the study, with 1380 (55.3%) receiving adalimumab, 608 (24.4%) receiving ustekinumab, 271 (10.9%) receiving secukinumab, 166 (6.7%) receiving etanercept and 71 (2.8%) receiving infliximab. The mean age at initiation of biologics was 43.6 years (standard deviation (SD) 15.2 years), and most patients were male (62.9%). During the follow‐up of 5477 patient years, 1953 patients (78.2%) reached the main endpoint of discontinuation. Using a log‐rank test, the probability of remaining on treatment was unaffected by the three definitions of complexity of the treatment journey.None of the three exposures used to assess the complexity of the pre‐biologic treatment journey appeared to impact drug survival. As long as patients experience adequate disease control, these results suggest that conventional systemic treatment do not negatively impact the drug survival of subsequent biologics. [ABSTRACT FROM AUTHOR]