Advances in Technology for Melanoma Diagnosis and Prognosis: An Expert Consensus Panel.

BACKGROUND: Cutaneous melanoma (CM) is associated with a higher mortality rate than most other skin cancers. The purpose of this expert consensus panel was to review the published literature on new technological advancements for the diagnosis and prognosis for CM and provide updated guidance on their usage. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the topics of non-invasive diagnostic and prognostic testing for CM, including gene expression profiling (GEP) and electrical impedance spectroscopy (EIS). A panel of 10 dermatologists with significant expertise in the treatment of CM gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using widely recognized Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 200 articles that met the criteria. A screening of the studies resulted in 19 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 5 of which were given a strength of "A", 1 of which was given a strength of "B," and 1 of which was given a strength of "C". CONCLUSION: The 2-GEP test and EIS can aid in the precise diagnosis of clinically indeterminate lesions and the 23-GEP test can be used when histopathology is equivocal. The 31-GEP test can enhance prognostic assessment beyond AJCC8 staging and improve clinical decision-making. J Drugs Dermatol. 2024;23(9):774-781. doi:10.36849/JDD.8365R1.

Notalgia Paresthetica Dermatologist Report of Symptom Burden and Treatment: Results from a Physician Survey.

Notalgia paresthetica (NP) is a sensory neuropathy characterized by chronic pruritus, skin pain, and other pathologic sensations affecting the mid-to-upper back. NP may be under-recognized and under-diagnosed, with limited data available on its symptom presentation and treatment patterns. NP-DERM was an internet-based survey of dermatologists (n = 650) from 8 different countries on their perspectives on NP symptoms and current treatment practices. Dermatologists typically treated a median of 12 patients with NP per month. Dermatologists reported that itch (pruritus) was the most common symptom for their patients with NP, followed by hyperpigmentation and sensitive skin. The most burdensome NP symptom was pruritus, followed by burning or hot sensation, and painful or raw skin. The most prescribed treatments included non-medicated skin care, topical corticosteroids, oral antihistamines, medicated topicals, and gabapentin or pregabalin. Physicians reported low satisfaction with available treatments. The most common reason for physicians to discontinue patients' therapy was lack of response.

Complete Skin Clearance is Associated with the Greatest Benefits to Health-Related Quality of Life and Perceived Symptoms for Patients with Psoriasis.

INTRODUCTION: With newer biologics, the achievement of complete skin clearance has become an attainable treatment goal for patients with plaque psoriasis. We evaluate how improvements in Psoriasis Area and Severity Index (PASI) responses, particularly at incremental improvements approaching complete skin clearance (PASI 100), translate into improvements in health-related quality of life (HRQoL) and patient-perceived symptoms. METHODS: Data from the BE RADIANT phase 3b trial (NCT03536884) and its open-label extension (OLE), pooled across all study visits and treatments over 16 weeks (randomised patients) and 2 years (patients entering the OLE), were analysed using mixed-effects logistic regression models. Proportions of patients achieving a Dermatology Life Quality Index (DLQI) of 0/1, DLQI item scores of 0, and Psoriasis Symptoms and Impacts Measure (P-SIM) item scores of 0 for itching, scaling, and skin pain at specific PASI improvement levels were estimated. RESULTS: Seven hundred and forty-three patients were randomised to treatment; 654 entered the OLE. Using 16-week pooled data, there were incremental improvements in the proportions of patients estimated by our model to achieve DLQI 0/1 with PASI 100 compared with 95% (PASI = 95%) and 90% (PASI = 90%) improvements in PASI (93.0%, 89.3%, and 83.8% achieving DLQI 0/1, respectively). Estimated proportions achieving DLQI item scores of 0 had the greatest increases at higher PASI improvement levels for Items 1 (itchy, sore, painful, or stinging skin), 2 (embarrassment), and 4 (choice of clothing). Estimated proportions of patients achieving P-SIM = 0 were also higher for PASI 100 (itching: 61.7%; scaling: 82.2%; skin pain: 96.9%) than for PASI = 95% (50.8%; 72.3%; 95.7%) and PASI = 90% (39.8%; 59.5%; 94.0%). Similar benefits of incremental PASI improvements were estimated using 2-year data. CONCLUSIONS: Complete skin clearance translated into the greatest benefits to HRQoL and patient-perceived symptoms, over and above skin clearance between 90% and 100%, highlighting the importance of targeting PASI 100 as a treatment outcome for patients with psoriasis. TRIAL REGISTRATION NUMBER: NCT03536884. Complete skin clearance is associated with the greatest benefits to health-related quality of life and perceived symptoms for patients with psoriasis: KeyResults and Conclusions (MP4 72828 kb).

Impact of Disease Factors of Patients with Psoriasis and Psoriatic Arthritis on Biologic Therapy Switching: Real-World Evidence from the CorEvitas Psoriasis Registry.

INTRODUCTION: Patients with psoriasis (PSO) and psoriatic arthritis (PsA) may frequently switch biologic therapies over the course of treatment because of symptom variability and individual responses. Real-world studies analyzing patient characteristics and clinical factors associated with biologic switching are limited. METHODS: This longitudinal cohort study used real-world data from the CorEvitas Psoriasis Registry to evaluate the relationship between associated disease factors and biologic switching among patients with PSO and PsA in the United States (US) and Canada following initiation of a biologic. Patients were evaluated between April 2015-August 2022. Combinations of disease severity (as measured by Psoriasis Area Severity Index [PASI]) and Dermatology Life Quality Index (DLQI) as a measure of health-related quality of life (HRQoL) were assessed, and the association with time to switching was calculated using Cox proportional hazards regression modeling. RESULTS: Among 2580 patient-initiations (instances of patients initiating a biologic), 504 (19.5%) switched biologics within 30 months of initiation. Switching was more frequent when either PASI > 10 or DLQI > 5 compared with PASI ≤ 10 or DLQI ≤ 5 at follow-up. Patients with higher skin involvement (PASI > 10) and impact on HRQoL (DLQI > 5) were 14 times more likely to switch (hazard ratio = 14.2, 95% confidence interval: 10.7, 18.9) than those with lower skin involvement (PASI ≤ 10) and HRQoL (DLQI ≤ 5). CONCLUSIONS: Patients with PSO and PsA treated in a real-world dermatology setting with substantial disease factors following biologic initiation were more likely to switch therapies. Those with PASI > 10 and DLQI > 5 switched more frequently than those with PASI ≤ 10 and DLQI ≤ 5.

Many patients with psoriasis may also have a related condition called psoriatic arthritis. Biologic medications work by helping to reduce inflammation and are commonly used to treat the symptoms of psoriasis and psoriatic arthritis. Patients might not all respond the same way to treatment and may need to change their medications over time. It is important we understand the reasons for switching medications to help patients better manage their symptoms.This study used information from a database on patients with both psoriasis and psoriatic arthritis. The database includes information on patients' medical history, including when they start and change their medication. We looked at data from patients who switched medications and patients who did not switch medications and examined differences in both how serious a doctor found their disease and the patients' own opinions of their overall health.We found that patients were more likely to change their biologic medication if they had more difficult psoriasis and psoriatic arthritis symptoms that caused worse skin problems, joint pain, and effects on their overall health compared with patients who had not changed their medication. These results suggest that it is important to consider both how serious a doctor finds their disease and patients' opinions of how much their symptoms affect their overall health. Understanding the reasons why patients switch medications will help to develop better ways of managing psoriasis and psoriatic arthritis.

Efficacy of Brodalumab in Patients with Psoriasis and Risk Factors for Treatment Failure: A Review of Post Hoc Analyses.

Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.

Interleukin-1α inhibitor bermekimab in patients with atopic dermatitis: randomized and nonrandomized studies.

Bermekimab is a human-derived recombinant monoclonal antibody that exhibits immunoregulatory activity by specifically blocking interleukin-1α activity. Four phase 2 studies evaluated efficacy and safety of bermekimab in patients with moderate-to-severe atopic dermatitis (AD). In addition, a novel human skin explant model was developed to assess bermekimab pharmacokinetics/pharmacodynamics and proteomic/transcriptomic effects. Study 1 (NCT03496974, N = 38) was an open-label, dose escalation study of subcutaneous bermekimab (200 mg or 400 mg). Study 2 (NCT04021862, N = 87) was a double-blind, placebo-controlled, randomized (1:1:1) study of subcutaneous bermekimab (400 mg every week (qw) or every 2 weeks) or placebo. GENESIS (NCT04791319, N = 198) was a double-blind, placebo- and active-comparator-controlled, randomized (1:1:2:2) study of placebo, subcutaneous bermekimab (350 mg or 700 mg qw), or dupilumab. LUNA (NCT04990440, N = 6) was a double-blind, placebo-controlled, randomized (4:1) study of intravenous bermekimab 800 mg qw or placebo. A novel human ex vivo skin pharmacodynamic assay supported phase 0 (NCT03953196) and phase 1 (NCT04544813) studies. In Study 1, 400 mg subcutaneous bermekimab showed improvement in efficacy assessments (e.g., ≥ 75% improvement of EASI over baseline, IGA 0/1, and worst itch); however, efficacy was not confirmed in Study 2 or GENESIS. Consequently, GENESIS and LUNA were terminated early. The novel human ex vivo skin pharmacodynamic assay demonstrated that bermekimab reduced downstream skin injury responses. Although bermekimab showed potential as an AD treatment in preclinical and early open-label trials, larger controlled studies (Study 2 and GENESIS) did not confirm those initial results.

Patient perspective on symptoms of Notalgia paresthetica: subpopulation results from the Neuropathic Itch Patient Survey (NIRVE).

Background: Notalgia paresthetica (NP) is a form of neuropathic itch characterized by recurrent itch in the mid back. Much about NP remains unclear, especially the patient experience.Objectives: The Neuropathic Itch Patient Survey (NIRVE) was a global, online survey conducted to better characterize the symptom burden of neuropathic itch from the patient perspective.Patients and methods: This report focuses on the symptom burden of the subpopulation of NIRVE participants with a self-reported diagnosis of NP (N = 91). Respondents reported visiting a median of 2 healthcare providers (HCPs) for their symptoms before receiving an accurate diagnosis of NP.Results: The most common cutaneous symptoms ever experienced were itch/pruritus, sensitive skin, painful or raw skin, numbness, and tingling. The symptoms reported by the most respondents as currently being experienced included itch/pruritus, numbness, painful or raw skin, tingling, and burning or hot sensation. Of patients currently experiencing symptoms, numbness and itch/pruritus were ranked as the most intense, followed by tingling, burning or hot sensation, and then painful or raw skin. Most patients consult multiple healthcare providers (HCPs) before receiving a diagnosis for their condition.Conclusion: Itch is overwhelmingly the most prevalent symptom of the condition, although half of patients also report experiencing sensitive skin, painful or raw skin, numbness, or tingling.

Current Treatments for Generalized Pustular Psoriasis: A Narrative Summary of a Systematic Literature Search.

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

Generalized pustular psoriasis (GPP) is a rare, chronic skin condition characterized by painful, sterile pustules that can occur all over the body. These pustules may also be accompanied by systemic inflammation, which can lead to serious health complications. GPP significantly impacts patients' quality of life and can even be life-threatening. Because the disease is so rare, treatment guidelines have typically been based on those for plaque psoriasis. However, these guidelines do not specifically address the unique needs of GPP. In this review, we analysed the published literature on GPP management, focussing on treatment efficacy, safety and quality of life outcomes. We searched the literature databases Embase and MEDLINE for articles published between 1980 and September 2023. In total, we identified 118 publications on this topic, covering a wide range of therapies; only one of these therapies, spesolimab, reported results from placebo-controlled randomized trials. Based on these trials, spesolimab is now approved for GPP treatment in the USA, Japan, China, the EU and several other countries. Some other therapies are approved exclusively in Japan and Taiwan based on small, open-label studies in the absence of higher-quality data. To date, comparing treatments has been challenging because of different clinical outcomes used to measure effectiveness. However, well-defined endpoints specific to GPP have recently been developed and used in trials. In conclusion, our review highlights the need for prospective randomized studies with GPP-specific endpoints to determine the best treatment strategy.

A randomized phase 3b study evaluating the safety and efficacy of risankizumab in adult patients with moderate-to-severe plaque psoriasis with non-pustular palmoplantar involvement.

BACKGROUND: In plaque psoriasis, palmoplantar areas are more difficult to treat. OBJECTIVE: Evaluate the safety and efficacy of risankizumab (RZB) versus placebo (PBO) for the treatment of palmoplantar psoriasis. METHODS: Patients were randomized to RZB or PBO for 16 weeks followed by RZB through week 52. The primary and secondary end points were achievement of palmoplantar Investigator's Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (ppIGA 0/1), achievement of ≥75%, ≥90%, and 100% improvement in Palmoplantar Psoriasis Area and Severity Index (PPASI 75, PPASI 90, PPASI 100) and achievement of static Physician Global Assessment of "clear" or "almost clear" with ≥2-point reduction from baseline (sPGA 0/1) at week 16. Safety was based on treatment-emergent adverse events. RESULTS: RZB demonstrated significant efficacy compared to PBO at week 16 in the patients achieving ppIGA 0/1 (33.3% vs 16.1% [P = .006]), PPASI 75 (42.5% vs 14.9% [P < .001]), PPASI 90 (27.6% vs 5.7% [P < .001]), sPGA 0/1 (32.2% vs 11.5% [P < .001]), and PPASI 100 (17.2% vs 1.1% [P < .001]). Results improved through week 52 with no new safety signals. LIMITATION: No biologic comparator. CONCLUSIONS: RZB demonstrated good tolerance and efficacy in palmoplantar psoriasis.

Dose escalation and associated economic outcomes in patients with psoriasis treated with biologics: A retrospective analysis of German health claims data.

BACKGROUND: In Germany, several biologic therapies are available for the treatment of moderate-to-severe plaque psoriasis, with the option of exceeding recommended dosages if standard dosing does not achieve a satisfactory treatment response. OBJECTIVES: To examine dose escalation in patients with biologic-treated psoriasis and associated cost development for German statutory health insurance (SHI). METHODS: We conducted a retrospective, non-interventional cohort study using German SHI health claims data from 2016 to 2021. Adult patients initiating biologic treatment were included in drug-specific cohorts. The odds for dose escalation, defined as the exceedance of the individually received daily dose over the maintenance dose recommended by the European product information, was compared between cohorts using multivariate logistic regression. The impact of dose escalation on SHI expenditures was analyzed with a generalized linear model. RESULTS: The relative frequency of dose escalation varied between cohorts (range 1.1% [risankizumab] to 42.9% [infliximab]). Compared to risankizumab-treated patients, the odds for dose escalation were statistically significantly (p < 0.05) higher in patients treated with all other biologic drugs except tildrakizumab. Patients with dose escalation during the maintenance phase accrued on average €6,473 more in direct healthcare costs to the SHI over a one-year period compared to those without dose escalation, with statistical significance (p < 0.05) after controlling for differences in covariates. CONCLUSIONS: Compared to patients treated with other biologics, dose escalation during the maintenance phase was lowest among risankizumab-treated patients. Dose escalation was associated with higher costs and thus a higher economic burden for the German SHI.

Safety of Bimekizumab for Plaque Psoriasis: An Expert Consensus Panel.

BACKGROUND: Plaque psoriasis is a chronic, relapsing systemic illness that has a significant effect on quality of life. Bimekizumab is the first monoclonal antibody to target both interleukin (IL)-17A and IL-17F, and recently received Food and Drug Administration (FDA) approval for moderate to severe plaque psoriasis. Guidance is necessary regarding the safety of bimekizumab. METHODS: A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed for English-language original research articles on the safety of bimekizumab for moderate to severe psoriasis. A panel of 9 dermatologists and 1 rheumatologist with significant expertise in the treatment of psoriasis gathered to review the articles and create consensus statements on this new medication. A modified Delphi process was used to approve each statement, and strength of recommendation was assigned using the Strength of Recommendation Taxonomy criteria. RESULTS: The literature search produced 110 articles that met the criteria. A thorough screening of the studies for relevance to the research question resulted in 15 articles. These were distributed to all panelists for review prior to a roundtable discussion. The panel unanimously voted to adopt 5 consensus statements and recommendations, all of which were given a strength of "A". CONCLUSION: Bimekizumab has a safety profile consistent with other biologics, except for a higher risk of oral candidiasis. Its hepatic safety profile is comparable with other currently FDA-approved biologics for plaque psoriasis. In addition, the data do not support an association of bimekizumab with suicide, and the incidence of inflammatory bowel disease is not greater than the incidence of other IL-17 blockers. J Drugs Dermatol. 2024;23(8):592-599. doi:10.36849/JDD.8246.

Spesolimab Reduces Inflammation in Generalized Pustular Psoriasis: Molecular Characterization of Flare Treatment in EFFISAYIL 1.

EFFISAYIL 1 was a randomized, placebo-controlled study of spesolimab, an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. Treatment with spesolimab led to more rapid pustular and skin clearance versus treatment with placebo in approximately half of the patients. In this study, we present histologic, transcriptomic, and proteomic analyses of lesional and nonlesional skin and whole-blood samples collected from EFFISAYIL 1. Treatment with spesolimab led to a transition toward a nonlesional profile, with a downregulation of gene expressions in the skin of IL-36 transcripts (IL36α, IL36ß, IL36γ) and those associated with neutrophil recruitment (CXCL1, CXCL6, CXCL8), proinflammatory cytokines (IL6, IL19, IL20), and skin inflammation (DEFB4A, S100A7, S100A8). Changes were manifest at week 1 and sustained to week 8. At the systemic level, reductions in serum biomarkers of inflammation (IL-17, IL-8, IL-6) were sustained until 12 weeks after spesolimab treatment. Considerable overlap was observed in the spesolimab-induced changes in gene and protein expressions from skin and blood samples, demonstrating the molecular basis of the effects of spesolimab on controlling local and systemic inflammation. Data are consistent with the mode of action of spesolimab, whereby inhibition of the IL-36 pathway leads to subsequent reductions in the key local and systemic pathologic events associated with generalized pustular psoriasis flares.

Developing a questionnaire for assessing clinician- and patient-reported outcomes in actinic keratosis: Results from an expert panel.

Background: Current assessments on topical treatment attributes in actinic keratosis (AK) do not evaluate safety, effectiveness, and satisfaction from both clinician and patient perspectives, creating an unmet need for more comprehensive AK-specific measures that fully capture the patient experience. Objective: To develop an actinic keratosis-specific expert panel questionnaire (AK-EPQ) of patient-reported outcomes and clinician-reported outcomes for use in research studies. Methods: Using interviews of patients with AK and targeted literature reviews, a 9-person consensus panel of dermatologists with expertise in AK treatment was convened to develop the AK-EPQ to assess AK-specific patient-reported outcomes and clinician-reported outcomes. Results: Nine expert advisers achieved consensus on 11 AK-EPQ items that encompass patient and clinician perspectives of treatment-related local skin reactions, clinical and cosmetic outcomes associated with AK, and satisfaction with treatment; the AK-EPQ will be first implemented in the Patient-Reported Outcomes for Actinic Keratosis study (NCT05260073). Limitations: The AK-EPQ does not directly measure quality of life, although it can be used with validated quality of life instruments. Conclusion: The newly developed AK-EPQ elicits insights into the patient and clinician experience with AK treatments. Comparative probing of these perspectives may help optimize precision medicine in AK treatment.

Six-Month Real-World Study to Assess the Effectiveness of Ixekizumab After Switching from IL-23 Inhibitors and Other Biologic Therapies: The CorEvitas Psoriasis Registry.

BACKGROUND: Prior work showed that patients from the CorEvitas Psoriasis Registry who had previously failed a prior biologic and then initiated ixekizumab demonstrated improvements in disease severity and patient-reported outcomes after 6 months. However, newer therapies such as interleukin-23 inhibitors (IL-23i) were not considered. Here, with more recent data including IL-23i, 6-month effectiveness of ixekizumab following a switch from any biologic was assessed as well as whether 6-month effectiveness of ixekizumab was impacted by prior biologic class. METHODS: We included CorEvitas Psoriasis Registry patients who initiated ixekizumab after discontinuing another biologic therapy and had a corresponding 6-month follow-up visit following ixekizumab initiation (N = 743, 2016-2023). Immediate prior biologic class was categorized as tumor necrosis factor inhibitor (TNFi) or interleukin-12/23 inhibitors (IL-12/23i, n = 405), non-ixekizumab interleukin-17i (IL-17i, n = 237), or IL-23i (n = 101). Adjusted mean changes in body surface area (BSA), Dermatology Life Quality Index (DLQI), itch, and skin pain were calculated for prior biologic class groups using analysis of covariance (ANCOVA). Proportions achieving ≥ 75%, ≥ 90%, and ≥ 100% improvement in Psoriasis Area and Severity Index (PASI75, PASI90, and PASI100, respectively), Investigator's Global Assessment (IGA) 0/1, and DLQI 0/1 were calculated for all patients and compared among prior biologic classes via relative risks (RRs) and 95% confidence intervals (CIs) using multivariable modified Poisson regression. RESULTS: Mean improvements in BSA, DLQI, itch, and skin pain, were 7.6, 3.6, 23.3, and 16.7, respectively, for ixekizumab patients who switched from TNFi or IL-12/23i (all p < 0.05); 6.8, 3.3, 19.6, and 14.1, respectively, for those who switched from non-ixekizumab IL-17i (all p < 0.05); and 7.8, 3.4, 22.2, and 12.8, respectively, for those who switched from IL-23i (all p < 0.05). Overall, 54%, 41%, and 31% of ixekizumab initiators achieved PASI75, PASI90, and PASI100, respectively, 50% maintained or achieved IGA 0/1, and 48% maintained or achieved DLQI 0/1. The prior TNFi or IL-12/23i group was 31% more likely to achieve PASI100 (RR = 1.31, 95% CI 1.01, 1.69) and 32% more likely to maintain or achieve IGA 0/1 (RR = 1.32, 95% CI 1.11, 1.57), but not significantly more likely to achieve PASI90. The prior IL-23i group was 45% more likely to achieve PASI90 (RR = 1.45, 95% CI 1.10, 1.91), 55% more likely to achieve PASI100 (RR = 1.55, 95% CI 1.12, 2.13), and 39% more likely to maintain or achieve IGA 0/1 (RR = 1.39, 95% CI 1.12, 1.73) compared to the prior non-ixekizumab IL-17i group. Achievement of PASI75 and DLQI 0/1 was consistent across the prior TNFi or IL-12/23i, IL-23i, and non-ixekizumab IL-17i groups. CONCLUSIONS: These updated findings with IL-23i data reaffirm that patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvement in disease severity and patient-reported outcomes at 6 months in real-world settings. Compared to patients who switched from another IL-17i, patients who switched class from a TNFi or IL-12/23i were more likely to achieve PASI100 and IGA 0/1, and patients who switched class from an IL-23i were more likely to achieve PASI90 in addition to PASI100 and IGA 0/1.

The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Psoriasis Comorbidities and Their Treatment Impact.

Psoriasis, a systemic inflammatory disease classically presenting with cutaneous lesions, has significant involvement in other organ systems. This article explores the prevalence, clinical manifestations, screening mechanisms, and laboratory testing by which to evaluate these comorbidities. Treatment approach for these comorbidities must combine patient preference with established treatment algorithms while recognizing innovative therapeutics currently under development.

Brodalumab: 5-Year US Pharmacovigilance Report.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Brodalumab is an injectable treatment approved for moderate-to-severe plaque psoriasis in adults who lacked response to previous treatments. In the USA, brodalumab is only available under a Risk Evaluation and Mitigation Strategy for increased suicidality risks; however, findings from 5 years of real-world safety data have demonstrated a lack of association. In this report, we discuss safety findings reported by US patients and healthcare providers for 4744 patients treated with brodalumab over 5 years. Joint pain (known as arthralgia) was the most common safety finding, with 122 cases reported over 5 years. Other safety findings of interest across 5 years included 106 serious infections (defined as prolonged infections or infections requiring treatment), 54 cases of depression, 49 cases of cancer (in 42 patients), 40 confirmed cases of COVID-19, and 11 cases of major cardiovascular events (such as stroke or heart attack). No completed suicides occurred throughout 5 years, and no new suicidal attempts were reported in year 5. In indirect comparisons with safety data from patients with psoriasis receiving or eligible to receive similar treatments, brodalumab was not associated with an increased risk of serious infection, cancer, major cardiovascular events, or inflammatory bowel disease. Taken together, these data are consistent with safety findings from long-term clinical trials and previous safety reports of brodalumab.