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BackgroundPatients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma.ObjectiveThe aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD.MethodsThis analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates.ResultsOf 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis. Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis. Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16. Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes. Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52. Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018). Plain Language Summary: Atopic dermatitis, or eczema, is a condition that causes painful itchy dry skin, which is burdensome for patients and has a negative impact on quality of life. These symptoms frequently lead to disruption of daily activities such as school and work, decreased self-confidence, social isolation, anxiety, depression, and sleep disturbance. Symptoms of atopic dermatitis, such as itch and sleep disturbance, can only be assessed by patients. Therefore, it is important to consider patients' perceptions of their symptoms and the related impact on their quality of life, especially when evaluating treatment benefits. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. In two clinical trials (Measure Up 1 and Measure Up 2), we investigated how treatment with upadacitinib (15-mg or 30-mg dose) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis would impact their symptoms and quality of life over a 1-year period. We measured changes over time in patients' assessments of itch, pain, other skin-related symptoms, sleep, daily activities, emotional state, mental health, and overall quality of life. Patients treated with upadacitinib experienced improvements in symptoms of atopic dermatitis and quality of life within the first 1–2 weeks of treatment. These improvements continued to steadily increase in the following weeks and lasted through 1 year of treatment. In conclusion, once-daily treatment with upadacitinib 15 or 30 mg led to early and lasting improvements in the well-being of patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare but severe skin inflammatory disorder characterized by the eruption of widespread sterile neutrophilic pustules, often accompanied by systemic inflammation. Given its life-threatening potential, GPP requires prompt accurate diagnosis and effective treatment, but its rarity and relapsing-remitting nature pose challenges in performing large-scale randomized controlled clinical trials. Established international guidelines are currently lacking and management guidance often follows that for plaque psoriasis. However, while it can co-exist with plaque psoriasis and has traditionally been classified as a most severe form of psoriasis, GPP is now recognized as a distinct entity, with its own clinicopathological, autoinflammatory, immunologic and genetic features. Research conducted over the past decade revealed that an imbalance of interleukin (IL)-36 signaling favoring the proinflammatory activity is the central driver of the pathogenesis of GPP, thereby laying the groundwork for the development of targeted therapies for the disease. This article reviews the evidence thus far on spesolimab, a selective humanized antibody against the IL-36 receptor that was recently licensed in Europe and the United States for the treatment of GPP flares in adults. In phase II, randomized controlled clinical trials, spesolimab led to rapid and effective skin clearance in patients experiencing a GPP flare and demonstrated superiority to placebo in preventing flares for up to 48 weeks with maintenance treatment, with reassuring safety and tolerability profiles. Spesolimab is considered to be a first-in-class medication establishing itself as the standard of care for the treatment of GPP flares, thus changing the paradigm of the management of GPP to a new era of scientifically- and evidence-based targeted therapy for this distinctive disease. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic eczematous lesions. The effect of treatment withdrawal after response to upadacitinib oral treatment is not fully characterized. Objectives: Assess the effect of upadacitinib withdrawal on skin clearance and itch improvement in adult patients with moderate‐to‐severe AD and evaluate the kinetics of recovery on rescue treatment. Methods: Data from a phase 2b randomized, placebo‐controlled trial (NCT02925117) of upadacitinib in patients with moderate‐to‐severe AD were analysed. Patients were randomized 1:1:1:1 to receive upadacitinib 7.5 mg, 15 mg, 30 mg or placebo, and then at Week 16, patients were re‐randomized 1:1 to receive the same dose of upadacitinib (upadacitinib 30 mg for patients initialized to placebo) or placebo. From Week 20, those who experienced loss of response defined as Eczema Area and Severity Index <50% improvement from baseline (EASI 50) received rescue treatment with upadacitinib 30 mg. Results: Patients who withdrew from upadacitinib experienced a rapid loss of skin clearance response, while those who switched from placebo to upadacitinib gained response. Loss of skin clearance response occurred within 4 weeks and worsening of itch occurred within 5 days. In patients who originally received placebo or a lower dose of upadacitinib leading to a loss of EASI response, rescue treatment with upadacitinib 30 mg resulted in rapid recovery or improvement of both skin and itch responses; most patients who were re‐randomized to placebo achieved EASI 75 and IGA 0/1 by 8 weeks of rescue treatment. No new safety risks were observed. Conclusions: Continuous treatment with upadacitinib is suggested to maintain skin clearance and antipruritic effects. [ABSTRACT FROM AUTHOR]

Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis. The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16. POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254). At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P <.0001 vs placebo; P =.0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P <.0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters. The study duration was 1 year. Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Effective, well-tolerated oral psoriasis treatments are needed. To compare the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, versus placebo and apremilast in adults with moderate to severe plaque psoriasis. Participants were randomized 2:1:1 to deucravacitinib 6 mg every day (n = 332), placebo (n = 166), or apremilast 30 mg twice a day (n = 168) in the 52-week, double-blinded, phase 3 POETYK PSO-1 trial (NCT03624127). Coprimary end points included response rates for ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment score of 0 or 1 (sPGA 0/1) with deucravacitinib versus placebo at week 16. At week 16, response rates were significantly higher with deucravacitinib versus placebo or apremilast for PASI 75 (194 [58.4%] vs 21 [12.7%] vs 59 [35.1%]; P <.0001) and sPGA 0/1 (178 [53.6%] vs 12 [7.2%] vs 54 [32.1%]; P <.0001). Efficacy improved beyond week 16 and was maintained through week 52. Adverse event rates with deucravacitinib were similar to those with placebo and apremilast. One-year duration, limited racial diversity. Deucravacitinib was superior to placebo and apremilast across multiple efficacy end points and was well tolerated in moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Fixed-dose combination topical therapy with corticosteroid and vitamin D analog provides effective treatment and possible long-term management of psoriasis. The anti-inflammatory and immunomodulatory effects of corticosteroids and vitamin D analogs in treating psoriasis are well investigated; their complementary effects lead to the disruption of the inflammatory feedback loop underlying psoriasis pathogenesis. Recent preclinical data showed that combination therapy is more effective than monotherapies of the active ingredients in preventing activation of resting pro-inflammatory cells, inducing immunomodulation, reducing inflammatory responses by regulating T cell production, and normalizing keratinocytes. The increased understanding of the mechanism of action of fixed-dose combination therapy from preclinical studies is supported by several clinical studies. As the efficacy of topical therapy is correlated with the skin penetration of the active ingredients, new drug delivery systems have been developed. The fixed-dose combination Cal/BD aerosol foam creates a modified supersaturated formulation when applied to the skin, which is maintained for at least 26 h in the laboratory setting. Clinical studies have demonstrated superior efficacy of fixed-dose combination calcipotriol (Cal) 50 μg/g and betamethasone dipropionate (BD) 0.5 mg/g aerosol foam compared with monotherapies of the active ingredients. Furthermore, Cal/BD aerosol foam has shown significantly improved efficacy compared with more traditional formulations, such as Cal/BD ointment and gel, in other studies. Calcipotriol also mitigates risks associated with betamethasone dipropionate and vice versa, resulting in the favorable safety profile observed with fixed-dose combination treatment. Recent data also suggest that fixed- dose combination treatment could provide long-term management of psoriasis, although further clinical investigations are needed. Overall, these data support the value of fixed- dose combination therapy of corticosteroid and vitamin D analog and highlight the added potential of innovative drug delivery for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Background: Leflunomide has shown promise in the treatment of psoriasis. Objective: To provide an in-depth analysis of the effect of leflunomide on psoriasis in patients with psoriatic arthritis (PsA). Methods: 190 patients with plaque psoriasis (at least 3% skin involvement) and active PsA were randomized to double-blind treatment with leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. Results: As previously reported, leflunomide resulted in a significantly higher Psoriatic Arthritis Response Criteria response rate than placebo (58.9 vs. 29.7%; p < 0.0001). Significant differences in favor of leflunomide were also observed in the Psoriasis Area and Severity Index (PASI 50 in 30.4% of patients vs. 18.9% for placebo; p = 0.05), target lesion response (46.4 vs. 25.3%; p = 0.0048), combined skin and joint response (27.2 vs. 8.9%; p < 0.0001), Dermatology Life Quality Index (improvement of 1.9 points vs. 0.2; p = 0.0173) and certain SF-36 subdomains. Dermatological responses were observed at the earliest examination (4 weeks) and increased throughout the 24-week study. Conclusion: Once-daily oral leflunomide is an effective and convenient treatment for PsA and plaque psoriasis. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

INTRODUCTION: A calcipotriene/betamethasone dipropionate two-compound product (Taclonex ointment) has been shown to be safe and effective in the treatment of psoriasis over 4 weeks. Since treatment of psoriasis is generally long-term, the objective of this study was to investigate the efficacy and safety of transferring patients to maintenance treatment with calcipotriene cream (Dovonex cream) following a 4-week treatment period with the two-compound product. METHODS: Patients with psoriasis were randomized to one of the following three treatment groups: 4 weeks of the two-compound product followed by 8 weeks of calcipotriene cream (calcipotriene cream group); 4 weeks of the two-compound product followed by 8 weeks of calcipotriene cream on weekdays and the two-compound product on weekends (alternating group); 4 weeks of the two-compound product followed by 8 weeks of vehicle of calcipotriene cream (vehicle group). All medications were applied once daily. RESULTS: A total of 1136 patients were randomized: 383 to the calcipotriene cream group, 377 to the alternating group, and 376 to the vehicle group. The mean percentage change in the Psoriasis Area and Severity Index from baseline to the end of the trial was −44.5% in the calcipotriene cream group, −58.4% in the alternating group, and −33.1% in the vehicle group. The mean difference between the calcipotriene cream and vehicle groups (primary treatment comparison) was −11.7% (95% CI −17.9, −5.5), which was statistically significant (p < 0.001), and the mean difference between the alternating and vehicle groups was −24.7% (95% CI −30.9, −18.5), which was also statistically significant (p < 0.001). For the investigators’ global assessment of disease severity at the end of the trial, the differences between the calcipotriene cream and vehicle groups, and between the alternating and vehicle groups, were statistically significant (p < 0.001), showing superior efficacy in the nonvehicle groups. The results were similar for the patients’ global assessment of response to treatment. There were 43 patients (11.3%) with adverse drug reactions in the calcipotriene cream group, 28 (7.6%) in the alternating group, and 32 (8.6%) in the vehicle group. There were no statistically significant differences in the incidence of adverse drug reactions in the calcipotriene cream group relative to the vehicle group (odds ratio 1.36; 95% CI 0.84, 2.21; p = 0.21), or in the alternating group relative to the vehicle group (odds ratio 0.87; 95% CI 0.51, 1.48; p = 0.61). CONCLUSION: Four weeks of treatment with the calcipotriene/betamethasone dipropionate two-compound product followed by 8 weeks of maintenance treatment with calcipotriene cream is effective and safe. As an alternative maintenance regimen, treatment with calcipotriene cream on weekdays and the two-compound product on weekends is also effective and safe. [ABSTRACT FROM AUTHOR]

Acrodermatitis continua of Hallopeau (ACH) is a rare type of pustular psoriasis affecting the digits. We report on a 43-year-old female patient who had been suffering from ACH for more than 20 years. Despite the fact that the disease was localized on one finger during the whole period, several topical and systemic treatments resulted in only temporary or partial improvement of the lesion. Although the monotherapies with calcipotriol and tacrolimus ointments gave no satisfying results in the long-term management of the disease, the combination of both agents led to a continuous improvement of the patient’s skin condition. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Dexpanthenol is popular in treating various dermatoses and in skin care, but few controlled clinical trials have been performed. We investigated the efficacy of dexpanthenol in skin protection against irritation in a randomized, prospective, double-blind, placebo-controlled study. 25 healthy volunteers (age 18–45 years) were treated for the inner aspect of both forearms with either Bepanthol® Handbalsam containing 5% dexpanthenol or placebo ×2 daily for 26 days. From day 15–22, sodium lauryl sulfate (SLS) 2% was applied to these areas ×2 daily. Documentation comprised sebumetry, corneometry, pH value and clinical appearance (photographs). 21 volunteers completed the study, 3 were excluded because of non-compliance and 1 experienced a non-study-related, severe, adverse event. Only corneometry yielded a statistically significant difference, with decreased values following SLS challenge at the placebo sites ( P < 0.05). Intraindividual comparisons showed superior results at the dexpanthenol-treated sites in 11 cases and in only 1 case at the placebo site. 6 volunteers experienced an irritant contact dermatitis, with more severe symptoms at the placebo site in 5 cases. In conclusion, dexpanthenol exhibits protective effects against skin irritation. The initiation of a study to evaluate the efficacy of dexpanthenol in preventing irritant occupational contact dermatitis under real workplace conditions is validated. [ABSTRACT FROM AUTHOR]