Dermatology and Therapy最新文献

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.

Introduction

Due to variable psoriasis symptoms, disease progression, and individual responses to therapy, patients may start, stop, or switch biologic therapies. Real-world data on the associated disease burden of patients with psoriasis who do and do not switch biologics are incomplete.

Methods

This study compared disease burden among patients from the CorEvitas Psoriasis Registry (July 2017–December 2021) who switched biologics and those who did not within 4–12 months following initiation. Disease-related patient-reported outcomes (PROs) were recorded, including skin pain, itching, activity impairment, and effects on health-related quality of life (HRQoL). Disease severity was measured by body surface area (BSA) and Psoriasis Area and Severity Index (PASI). Unadjusted and adjusted regression models were used to compare study outcome measures between the two groups.

Results

This study included 2145 patients, with 159 classified as switchers and 1986 as non-switchers. The most common reason for switching therapy was failure to maintain initial response (51.7%; n = 78). Moderate-to-severe disease (BSA ≥ 3) was found among 83.0% (n = 132) of switchers versus 26.1% (n = 516) of non-switchers. PASI > 5 was reported among 49.7% (n = 79) of switchers versus 8.6% (n = 171) of non-switchers. Differences in skin pain, itching, and effects on HRQoL between switchers and non-switchers were larger in magnitude for bio-experienced patients.

Conclusions

Patients who switched biologic therapy experienced a greater disease burden of psoriasis across PROs than non-switchers. Patient-centered factors may be important drivers of biologic switching. Our findings suggest the association between switching and disease burden may be stronger among patients with prior biologic therapy experience.

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.

Background

Psoriasis, a chronic, immune-mediated, inflammatory disease, affects 2‒3% of the population. Tyrosine kinase 2 (TYK2) mediates cytokine signaling involved in adaptive [interleukin (IL)-12, IL-23] and innate (type-I interferons) immune responses; IL-23–driven T-helper (Th)17 pathways play a key role in chronic inflammation in psoriasis. In a phase 2 trial, deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, reduced IL-23/Th17 and type-I interferon pathway expression in the skin of patients with moderate to severe plaque psoriasis, reductions that were accompanied by clinical improvement of psoriatic lesions.

Objectives

The aim of this study was to identify biomarkers of psoriatic disease in serum from patients enrolled in the phase 2 trial and to assess the effects of deucravacitinib on those biomarkers.

Methods

Serum biomarkers from Olink proteomics and other quantitative assays were evaluated for a pharmacodynamic response to deucravacitinib treatment and correlation with psoriasis disease activity measures.

Results

Serum biomarkers associated with the IL-23/Th17 pathway [IL-17A, IL-17C, IL-19, IL-20, beta-defensin, and peptidase inhibitor 3 (PI3)] were upregulated in patients with psoriasis versus healthy controls. Deucravacitinib treatment reduced IL-17A (adjusted mean change from baseline at Day 85; 12 mg once daily versus placebo; −0.240 versus −0.067), IL-17C (−14.850 versus −1.664), IL-19 (−96.445 versus −8.119), IL-20 (−0.265 versus −0.064), beta-defensin (−65,025.443 versus −7553.961), and PI3 (−14.005 versus −1.360) expression. Reductions in serum biomarker expression occurred in a dose- and time-dependent manner, with significant reductions from baseline seen with deucravacitinib doses ≥ 3 mg twice daily (P ≤ 0.05). Biomarker expression correlated with disease activity measures such as Psoriasis Area and Severity Index (PASI) at baseline. Biomarker expression also correlated with PASI scores at Week 12.

Conclusion

IL-23/Th17 pathway expression in the serum of patients with psoriasis is an indicator of disease activity and response to deucravacitinib treatment.

Trial registration number

NCT02931838.

This narrative literature review examined the intricate relationship between body dysmorphic disorder (BDD) and dermatological conditions, with a brief focus on those characterized by conspicuous skin irregularities such as acne vulgaris, psoriasis, and vitiligo. Highlighting the significant prevalence of BDD among individuals afflicted with dermatological issues, our analysis illuminated the profound psychological repercussions stemming from an exaggerated preoccupation with perceived skin imperfections. Through an exploration of the underlying BDD symptoms, we analyzed the complex dynamics between skin health and mental well-being, emphasizing the disorder’s impact on patients’ psychological and social functioning. This narrative review further investigated the consequential effects of BDD on essential aspects of dermatological treatment, including patient adherence to therapeutic regimens, overall quality of life (QOL), and the effectiveness of available treatments. In addition to presenting current therapeutic approaches, we advocate for the integration of psycho-dermatological interventions tailored to mitigate the dual burden of skin conditions and psychological distress. Future research directions proposed include longitudinal studies to assess the long-term effects of BDD on skin disease prognosis and psychosocial well-being, which aim to refine and optimize treatment modalities to contribute to a more holistic understanding of BDD within dermatological practice.

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.

Background

Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments.

Objectives

The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures.

Methods

Adult (≥ 18 years) patients (N = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients’ experiences of DM, including the symptoms and impacts on their daily lives and wellbeing.

Results

Patients reported 13 different skin manifestations of DM. The most common were rash (n = 28, 100%), itch (n = 28, 100%), dry skin (n = 23, 82%), and swelling of the skin (n = 17, 61%). The head and face, followed by hands, were perceived as the most bothersome body areas affected by skin manifestations, because they are exposed and visible to themselves and other people. All patients (n = 28, 100%) reported at least one impact of DM, which varied greatly between patients, but included emotional, psychological, cognitive, and physical impacts, and those affecting daily life, such as work and sleep. Over half of the patients (n = 19, 67%) reported that their daily activities were impacted by DM.

Conclusions

The qualitative interviews with patients revealed that the presentation of DM manifestations is highly variable but affects patients’ emotional wellbeing, physical activities, and daily life significantly.

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.

Methods

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.

Results

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).

Conclusions

Prior AA treatment history had no effect on longer-term treatment response to ritlecitinib.

Trial Registration Number

NCT03732807.

Graphical Abstract

Oral Janus kinase inhibitors (JAKi), a class of advanced targeted systemic therapy, have demonstrated efficacy and safety in the treatment of moderate-to-severe atopic dermatitis (AD). Like other small molecules, oral JAKi have the potential for off-target effects including laboratory-related adverse events (AEs). Product labels for oral JAKi recommend an initial laboratory assessment and follow-up 4-12 weeks later to monitor for potential changes, based on evidence from clinical trials across therapeutic indications for oral JAKi, which may not reflect a population of moderate-to-severe AD patients typically seen in routine clinical practice. To address this gap, a panel of eight dermatologists with clinical and research experience with oral JAKi for the management of AD conducted a targeted review of the literature focused on key laboratory-related AEs associated with oral JAKi in the moderate-to-severe AD population. Based on the synthesis of evidence and informed opinion, a set of best practice statements related to fundamental standards of care and consensus recommendations on laboratory monitoring were suggested, and level of agreement was ascertained using a Likert scale from 0 to 100. There was a high level of agreement on three of the four suggested recommendations related to assessment and monitoring of key laboratory parameters and to dose reduction or switching in response to laboratory changes; there was a lower level of agreement related to the frequency of ongoing laboratory monitoring. Appropriate patient selection and laboratory assessment is an important strategy to mitigate the potential risks associated with oral JAKi when treating AD.

Atopic dermatitis often begins in infancy and follows a chronic course of exacerbations and remissions. The etiology is complex and involves numerous factors that contribute to skin barrier defect and inflammation. In the Middle East, the burden of atopic dermatitis is understudied. Epidemiological data specific to the Gulf region are scarce but reveal a prevalence of up to about 40% in the United Arab Emirates. Region-specific factors, such as the climate and the frequency of consanguineous marriages, may affect atopic dermatitis incidence, prevalence, and evolution over time. A panel of experts predominantly from the United Arab Emirates analyzed the evidence from published guidelines, and considered expert guidance and local treatment practices to develop clear recommendations for the management of atopic dermatitis in the United Arab Emirates. They encourage a systematic approach for the diagnosis and treatment, using disease severity scores and quality-of-life measurement tools. Treatment recommendations take into consideration both established therapies and the approved systemic biologics dupilumab and tralokinumab, and the Janus kinase inhibitors baricitinib, upadacitinib, and abrocitinib.