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Background: In the phase III double-blind Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) 1 and 2, apremilast, an oral phosphodiesterase 4 inhibitor, demonstrated efficacy in moderate to severe psoriasis., Objective: We sought to evaluate efficacy of apremilast in nail/scalp psoriasis in ESTEEM 1 and 2., Methods: A total of 1255 patients were randomized (2:1) to apremilast 30 mg twice daily or placebo. At week 16, placebo patients switched to apremilast through week 32, followed by a randomized withdrawal phase to week 52. A priori efficacy analyses included patients with nail (target nail Nail Psoriasis Severity Index score ≥1) and moderate to very severe scalp (Scalp Physician Global Assessment score ≥3) psoriasis at baseline., Results: At baseline, 66.1% and 64.7% of patients had nail psoriasis; 66.7% and 65.5% had moderate to very severe scalp psoriasis in ESTEEM 1 and 2. At week 16, apremilast produced greater improvements in Nail Psoriasis Severity Index score versus placebo; mean percent change: -22.5% versus +6.5% (ESTEEM 1; P < .0001) and -29.0% versus -7.1% (ESTEEM 2; P = .0052). At week 16, apremilast produced greater NAPSI-50 response (50% reduction from baseline in target nail Nail Psoriasis Severity Index score) versus placebo (both studies P < .0001) and ScPGA response (Scalp Physician Global Assessment score 0 or 1) versus placebo (both studies P < .0001). Improvements were generally maintained over 52 weeks in patients with Psoriasis Area and Severity Index response at week 32., Limitations: Baseline randomization was not stratified for nail/scalp psoriasis., Conclusion: Apremilast reduces the severity of nail/scalp psoriasis., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis., Objectives: ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis., Methods: This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast., Results: The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo (P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection., Conclusions: Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks., (© 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Increasingly, quality of life data are being captured along with other measures to evaluate success in the treatment of numerous disease states. This is no less true in hidradenitis suppurativa (HS), an inflammatory condition that features multiple symptoms, including abscesses that can develop in multiple sites on the body, often in sensitive areas, that can be painful, can rupture, and can produce malodorous pus. The collection of baseline data with respect to the personal impact of HS is a necessary first step to determine if various interventions enhance the quality of life for patients with HS. While no particular tool provides sufficient insight about the psychosocial impairment that HS promotes, myriad instruments that have been used to measure the quality of life of HS patients have consistently shown that the disease has a substantial adverse impact on the physical, social, and emotional well-being of patients., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Phosphodiesterase (PDE) 4 participates in regulating the inflammatory response by degrading cyclic adenosine 3'5'-monophosphate (cAMP), a key second messenger. Inhibition of PDE4 increases the intracellular cAMP level, which in turn results in a reduction in inflammatory mediators and an increase in anti-inflammatory mediators. Immune-modulating effects of PDE4 inhibitors have been investigated in a number of inflammatory conditions, such as asthma, atopic dermatitis, chronic obstructive pulmonary disease, Behçet’s disease, psoriasis, and psoriatic arthritis. Apremilast, a selective PDE4 inhibitor, has been shown to block the production of pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-12, IL-17, and IL-23), which are the key players in the pathogenesis of psoriasis. Increased intracellular cAMP levels result in a range of anti-inflammatory effects on numerous cell lines. A decrease in proinflammatory activity has been shown to result in a reduced psoriasiform response in preclinical in vivo models of psoriasis, and reduction of biologic activity in a pilot study in humans. The efficacy and safety of apremilast in the treatment of psoriasis have been demonstrated in phase II and III clinical trials. Apremilast demonstrated efficacy in reducing the severity of moderate to severe plaque psoriasis. Treatment with apremilast was well tolerated, with generally mild gastrointestinal complaints, which occurred early in the course of the treatment and resolved over time, and there was no requirement for laboratory test monitoring. These results make apremilast an attractive therapeutic option for plaque psoriasis.

Phosphodiesterase 4 (PDE4) is a key enzyme in the regulation of immune responses of inflammatory diseases through degradation of the second messenger, cyclic adenosine 3',5'-monophosphate (cAMP). Apremilast, a selective PDE4 inhibitor, has been shown to reduce the production of pro-inflammatory cytokines by increasing intracellular levels of cAMP and promoting the production of anti-inflammatory cytokines. The efficacy and safety of apremilast in the treatment of psoriasis and psoriatic arthritis has been demonstrated in phase 2 and 3 studies and will be reviewed here. Across all studies, treatment was generally well-tolerated with some mild gastrointestinal complaints that occurred early and resolved over time, resulting in few drop-outs. Meaningful changes in dactylitis and enthesitis were also observed. Routine monitoring is not required given the absence of drug associated physiologic, biochemical, and haematological changes. Apremilast proves to be a new promising systemic therapy for treating psoriatic disease.

Background: Methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) have been identified as potent allergens. The optimal MI concentration for patch testing for reaction to these agents has not yet been identified, but it has been suggested that testing MI at 2000 ppm may reduce false-negative reactions., Objective: The aim of this study was to report allergic reactions to MI and MCI/MI detected in a community dermatology practice setting in Ontario, Canada., Methods: The patch test records of patients with suspected allergic contact dermatitis seen between October 2007 and June 2014 were reviewed. We compared positive patch testing before and after December 2011 when a higher MI concentration was used (2000 ppm aqueous) in addition to the baseline series MCI/MI at 100 ppm., Results: A total of 794 patient records were reviewed. There were 38 true-positive reactions to MI or MCI/MI. Of these 38 patients, 26 (68%) were female. We detected an overall increase in the rate of positive patch testing to MCI/MI, MI alone, or both from 3.13% to 7.45% when MI concentration was introduced at 2000 ppm aqueous. Occupational differences existed between sexes., Conclusions: The addition of MI at 2000 ppm to our screening series effectively increased the detection of MI-induced allergic contact dermatitis.

Acting on keratinocytes to produce antimicrobial peptides and chemokines, which in turn attract neutrophils and other inflammatory cells, interleukin-17 (IL-17) is believed to be a potent driver of plaque psoriasis. Its proinflammatory characteristics make IL-17 an attractive therapeutic target for addressing immune dysregulation. This review examines the role of IL-17 in the pathogenesis of plaque psoriasis and the potential implications of its inhibition. The efficacy and safety results from Phase 2 and 3 trials with monoclonal antibodies targeting IL-17RA (brodalumab), and IL-17A (ixekizumab and secukinumab) validate IL-17 as an effective therapeutic target for the treatment of plaque psoriasis.

Psoriasis is a chronic condition which requires ongoing management with therapies that have demonstrated favorable safety and efficacy profiles in long-term use. While biologics changed the way psoriasis is treated by providing effective targeted therapy, they are not without limitations. However, small molecules are emerging therapeutic options for the treatment of psoriasis. Several oral and topical small molecules, spanning different therapeutic classes, are proving to be promising treatment options in psoriasis. While studies to date have yielded positive results, further investigation of these agents are warranted for both safety and efficacy.

Background: Once‐daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate‐to‐severe atopic dermatitis (AD) in randomized controlled studies. Objective: To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality‐of‐life (QoL) benefits. Methods: Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO‐1; NCT03575871/JADE MONO‐2) in adult and adolescent patients (N = 942) with moderate‐to‐severe AD receiving once‐daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]‐75 and ≥4‐point improvement in Pruritus Numerical Rating Scale [PP‐NRS4]) and higher threshold efficacy end points (EASI‐90 to

Rosacea is a common chronic skin disorder that has significant impact on the self-esteem and quality of life of affected individuals. Currently understood as an inflammatory condition that occurs in the context of an altered innate immune response, the available topical and systemic therapies function as immunomodulators to restore cutaneous homeostasis. The goals of therapy include reduction of papules, pustules, erythema and physical discomfort with improvement in quality of life. Standard topical treatments include metronidazole and azelaic acid, although many other agents and regimens have been presented. Subantimicrobial/antiinflammatory dose oral doxycycline was US FDA approved in 2006 for the management of rosacea, but Health Canada clearance was only recently granted for this indication. Furthermore, renewed research interest has led to the development of other emerging therapies including topical ivermectin, brimonidine and oxymetazoline that hold promise for patients suffering from this condition.

The incidence of nonmelanoma skin cancer continues to increase. While surgical excision remains the mainstay of treatment, growing demand from patients for effective, tissue-sparing approaches with good cosmetic results has led to the development of novel therapeutic agents. Several studies have reported on the safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia peplus, in the treatment of actinic keratosis and superficial basal cell carcinoma. An understanding of the history, mechanism of action, and recent trial evidence for this emerging therapy can assist physicians in counseling patients on available treatment options and in selecting appropriate therapy.

The common bedbug (Cimex lectularius) is increasingly prevalent and a source of concern and questions for patients. In addition to a range of cutaneous presentations and potential for serious sequelae, bedbug bites cause significant psychological distress and create an economic burden associated with infestation control. Recognition of characteristic entomology, clinical presentation, diagnostic features and differential diagnosis can support expedient identification of patients exposed to infestations and support their appropriate management.

Summary: Tildrakizumab 是一种相当新型的药物,称为生物制剂,用于治疗中度至重度牛皮癣。这种药物可以防止体内一种与炎症有关的特定分子的活动,这种分子被称为细胞因子白细胞介素 (IL)‐23p19。 先前的研究表明,它优于安慰剂(一种非活性物质,像"糖丸"一样)和一种旧的生物制剂,即 TNF 抑制剂 Etanercept。然而,试验很少反映出现实世界的经历,患者可能会从一种药物换到另一种药物,改变药物剂量或中断治疗,例如因为感染而这样做。 作者(位于美国、加拿大和德国)回顾了两项研究的结果,一项是将两种不同剂量的 Tildrakizumab(每天 100 mg 或 200 mg)与安慰剂进行比较,另一项是将其与 Etanercept 进行比较,其中纳入总共 1862 名患有中度到重度斑块型银屑病的成年患者。 在研究过程中,重新随机分配治疗。他们发现,对 Tildrakizumab 的应答是持续的(这意味着它持续起作用),没有出现一些使用 Etanercept 的患者中出现的继发性失败(在最初满意的应答后对药物的应答性下降),并且在治疗中断后,重新使用药物仍能有效地控制银屑病。总体而言,该药物耐受性良好,这意味着其副作用很小。 本摘要涉及研究:在持续给药、治疗中断、剂量调整和从 Etanercept 转换过来的情况下 Tildrakizumab 治疗斑块型银屑病的有效性和安全性: 来自 III 期研究的结果。 Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

Summary: Tildrakizumab is a fairly new type of medicine called a biologic, used for the treatment of moderate‐to‐severe psoriasis. The drug prevents the action of a specific molecule in the body involved in inflammation, known as cytokine interleukin (IL)‐23p19. Previous studies have shown it to be superior to a placebo (an inactive substance, like a "sugar pill") and to an older biologic drug, the TNF inhibitor etanercept. However, trials rarely reflect real‐world experience, where patients may switch from one drug to another, change drug dosage or interrupt treatment, e.g. because of an infection. The authors, based in U.S.A., Canada and Germany, reviewed results from two studies, one comparing two different doses of tildrakizumab (100mg or 200mg per day) with placebo, and the other comparing it with etanercept, including a total of 1862 adults with moderate‐to‐severe plaque psoriasis. Treatments were re‐randomised during the course of the study. They found that the response to tildrakizumab was sustained (meaning it kept working), without the secondary failure (decreasing responsiveness to a drug after an initial satisfactory response) seen in some patients on etanercept, and the drug regained effective control of the psoriasis after treatment was interrupted. Overall the drug was well tolerated, meaning that side effects were minimal. This is a summary of the study: Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

Many options exist for the treatment of rosacea, including topical and systemic therapies, laser and light-based therapies, and surgical procedures. A classification system for rosacea identifies 4 subtypes (i.e., erythematotelangiectatic, papulopustular, phymatous, and ocular), which may help guide therapeutic decision-making. The goals of therapy include reduction of papules, pustules, erythema, physical discomfort, and an improvement in quality of life. Standard topical treatment agents include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Second line therapies include benzoyl peroxide, clindamycin, calcineurin inhibitors, and permethrin.

Background: Lipodystrophy syndrome is a devastating complication of antiretroviral therapy in individuals with human immunodeficiency virus (HIV). The appearance of the associated facial lipoatrophy can be demoralizing and stigmatizing for the affected individuals to a point at which it may compromise their compliance with antiretroviral medication., Objective: We describe the use of hyaluronic acid as an intradermal filler for correction of this disfiguring problem., Methods: We treated five patients with grade 2 to 3 facial lipoatrophy. Each patient received approximately 5 to 6 cc in total of hyaluronic acid in the malar area via intradermal injection., Results: There were no adverse events. We found that this technique provided a good cosmetic result with high patient satisfaction. At 6-month follow-up, sustained longevity was observed., Conclusions: We propose the use of hyaluronic acid for HIV-associated facial lipoatrophy as an efficacious and safe, but temporary, option for this problem until a more cost-effective option is available.

Linked Article: Papp et al. Br J Dermatol 2019; 180:1352–1360 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a long‐lasting disease involving inflammation of the skin. In the most common form of this disease ‐ plaque psoriasis ‐ the inflammation is visible as raised, reddened and often scaly areas which may extend widely over the body. Although not generally a life‐threatening condition, psoriasis may increase the risk of other serious disorders (such as cardiovascular disease), and often leads to much reduced quality of life for patients ‐ through physical discomfort (itching, pain), disability, and related emotional trauma. Furthermore, psoriasis occurs worldwide (affecting up to 3% of the populations in various countries) and cannot be completely cured by available treatments. Together, these issues make the disease a serious global burden. Granulocyte‐Macrophage Colony‐Stimulating Factor (GM‐CSF) is made in the body and is important in controlling functions of the body's immune system and the processes involved in inflammation. Therefore, this study was carried out to establish whether blocking the activities of GM‐CSF in patients with moderate or severe plaque psoriasis could result in significant improvement of the disease. In total, 122 patients were enrolled from Canada, Denmark, Germany, Latvia and Poland. The patients were treated over 10 weeks either with namilumab (GM‐CSF blocker) or a placebo (inactive): assessments of their psoriasis were made during this period, and completed after an additional 2 weeks. Notably, throughout the 12‐week study duration no significant improvement was detected for namilumab‐treated patients ‐ in marked contrast to treatment benefit found in a similar study involving patients with rheumatoid arthritis. These findings point to different roles for GM‐CSF in the two diseases, and suggest that blocking GM‐CSF activity alone is not enough for effective treatment of plaque psoriasis. Linked Article: Papp et al. Br J Dermatol 2019; 180:1352–1360 [ABSTRACT FROM AUTHOR]

In addition, two patients used concomitant methotrexate for psoriatic arthritis and one concomitant alitretinoin for persistent palmoplantar involvement. A sub-analysis of 24 patients who had been on risankizumab for 12 months or greater revealed 46% of these patients had an IGA of 0, 37% IGA 1 and 17% IGA 2 (Fig. While most patients used 150 mg risankizumab every 12 weeks after the loading period, four had their frequency increased to every 8 weeks, one to every 6 weeks and one patient extended frequency to every 16 weeks. [Extracted from the article]

Background: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. Objectives: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate‐to‐severe AD. Methods: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate‐to‐severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. Results: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. Conclusions: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate‐to‐severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up). [ABSTRACT FROM AUTHOR]

Background: Limited data are available on long‐term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity. Objectives: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS. Methods: This was a post hoc analysis of the double‐blind, randomized, placebo‐controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure‐adjusted incidence rates (EAIRs) of treatment‐emergent adverse events (TEAEs). Results: reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100‐treated patients with MetS, 98 and 167 TIL100‐treated patients without MetS, 34 and 30 TIL200‐treated patients with MetS, and 111 and 130 TIL200‐treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100‐treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200‐treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS. Conclusions: Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status. [ABSTRACT FROM AUTHOR]

Hundred percent of patients who had no response to CA received three or fewer treatments and 72% received a concomitant therapy. Patient baseline characteristics, lesion location, number/quantity of CA dosages, concomitant therapies, adverse events and CA response were extracted. Most patients (81.3%) received a concomitant treatment, often cryotherapy (43.8%), with or without an adjunctive topical therapy for home application. [Extracted from the article]

Background: Psoriasis has important physical and psychosocial effects that extend beyond the skin. Understanding the impact of treatment on health‐related quality of life (HRQoL) and patient‐perceived symptom severity in psoriasis is key to clinical decision‐making. Objectives: This post hoc analysis of the PSO‐LONG trial data assessed the impact of long‐term proactive or reactive management with fixed‐dose combination calcipotriene 50 µg/g and betamethasone dipropionate 0.5 mg/g (Cal/BD) foam on patient‐reported outcomes (PROs) in patients with psoriasis vulgaris. Methods: Five hundred and twenty‐one patients from the Phase 3, randomized, double‐blind PSO‐LONG trial were included. An initial 4‐week, open‐label phase of fixed‐dose combination Cal/BD foam once daily (QD) was followed by a 52‐week maintenance phase, at the start of which patients were randomized to a proactive management arm (Cal/BD foam twice weekly) or reactive management arm (vehicle foam twice weekly). Patient‐perceived symptom severity and HRQoL were assessed using the Psoriasis Symptom Inventory (PSI), the Dermatology Life Quality Index (DLQI) and the EuroQol‐5D for psoriasis (EQ‐5D‐5L‐PSO). Results: Statistically and clinically significant improvements were observed across all PRO measures. The mean difference (standard deviation) from baseline to Week 4 was −8.97 (6.18) for PSI, −6.02 (5.46) for DLQI and 0.11 (0.15) for EQ‐5D‐5L‐PSO scores. During maintenance, patients receiving reactive management had significantly higher DLQI (15% [p = 0.007]) and PSI (15% [p = 0.0128]) and a numerically lower EQ‐5D‐5L‐PSO mean area under the curve score than patients receiving proactive management (1% [p = 0.0842]). Conclusions: Cal/BD foam significantly improved DLQI, EQ‐5D‐5L‐PSO and PSI scores during the open‐label and maintenance phases. Patients assigned to proactive management had significantly better DLQI and PSI scores and numerically better EQ‐5D‐5L‐PSO versus reactive management. Additionally, baseline flare was associated with worse PROs than the start of a relapse, and patients starting a relapse also had worse PROs than patients in remission. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS‐CoV‐2 is reflected by its rapid global spread. The SARS‐CoV‐2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS‐CoV‐2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS‐CoV‐2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms. [ABSTRACT FROM AUTHOR]

Background: Patients treated with tumour necrosis factor (TNF) inhibitors are at risk of new‐onset tuberculosis (TB) or reactivation of latent tuberculosis infection (LTBI). Association between TB/LTBI and interleukin (IL)‐23 inhibitors for psoriasis is unclear. Patients with LTBI typically initiate LTBI therapy before receiving biologics. Objectives: Safety in moderate‐to‐severe psoriasis patients with LTBI treated with guselkumab (IL‐23 inhibitor) and LTBI treatment was evaluated. Methods: In the VOYAGE 1 & VOYAGE 2 studies, patients screened for LTBI were randomized to guselkumab, placebo, or adalimumab (TNF inhibitor) at baseline. Placebo → guselkumab crossover occurred at week 16 and adalimumab → guselkumab at week 52 (VOYAGE 1), or at week 28 or later (VOYAGE 2). Incidence of active TB, adverse events (AEs), serious AEs (SAEs), and markedly abnormal liver function tests [alanine aminotransferase test (ALT); aspartate aminotransferase test (AST)] were evaluated using pooled data through week 100 in guselkumab‐treated patients receiving and not receiving LTBI treatment. Results: At baseline, 130 randomized patients (guselkumab: n = 69; adalimumab: n = 36; placebo: n = 25) tested positive for LTBI and received concomitant LTBI treatments (LTBI+). No active TB was reported among guselkumab‐treated patients without LTBI (LTBI−) through week 100. Two cases of active TB occurred in LTBI− patients treated with adalimumab. Through week 16, across all treatment groups, greater proportions of LTBI+ patients reported ALT and AST elevations compared with LTBI− patients. Through week 100, proportions of patients experiencing AEs and SAEs were comparable between LTBI+ and LTBI− patients. Conclusions: No cases of active TB, including reactivation of LTBI, were reported in patients with or without LTBI treated with guselkumab through up to 2 years. LTBI treatment was effective across all treatment groups in preventing reactivation of LTBI. Long‐term treatment with guselkumab was generally well‐tolerated through up to 2 years in patients receiving LTBI medications. [ABSTRACT FROM AUTHOR]

Background: Two randomized controlled trials (reSURFACE 1 and 2) have demonstrated the effectiveness of tildrakizumab, a high‐affinity, humanized, IgG1κ, anti‐interleukin‐23 monoclonal antibody, for treating moderate‐to‐severe plaque psoriasis in the first 28 weeks. Objectives: To examine the efficacy of tildrakizumab and its impact on quality of life (QoL) in patients with different levels of week‐28 Psoriasis Area and Severity Index (PASI) improvement. Methods: Patients treated with tildrakizumab 100 mg or 200 mg from baseline to week 28 were pooled from reSURFACE 1 and reSURFACE 2 and classified into five mutually exclusive week‐28 PASI improvement groups for each dose: PASI 0–49, 50–74, 75–89, 90–99 and 100. Mean PASI improvement and Dermatology Life Quality Index (DLQI) 0/1 over time were examined for each group. Results: Of 1156 patients, 575 were in the 100‐mg and 578 in the 200‐mg cohorts, respectively. At week 28, 8.3%, 14.3%, 23.8%, 30.4% and 23.1% in the 100‐mg and 4.0%, 18.1%, 19.6%, 29.1% and 29.3% in the 200‐mg cohort achieved PASI < 50, 50–74, 75–89, 90–99 and 100, respectively. Patients with PASI < 50 at week 28 could be identified as early as week 8, and those with week‐28 PASI ≥ 90 had approximately 50% PASI improvement by week 4. Among patients achieving PASI > 50 at week 28 who continued the same dose of tildrakizumab to week 52, mean PASI improvement was maintained or improved over time. Similar results were observed for both doses. Higher proportions of patients achieved DLQI 0/1 in higher week‐28 PASI groups, and DLQI 0/1 was maintained or improved to week 52. However, not all patients with PASI 100 had DLQI 0/1. Conclusion: Patients unlikely to respond to tildrakizumab could be identified by week 8, and those likely to achieve a PASI ≥ 90 response could be identified as early as week 4. Week‐28 PASI improvement level correlated with QoL improvement. [ABSTRACT FROM AUTHOR]

Abstract: Background: Palmoplantar psoriasis is a variant of psoriasis vulgaris which can severely impair quality of life. Objectives: The main objectives of this double‐blind, placebo‐controlled, randomized study were to assess the efficacy and impact on quality of life and work productivity of apremilast for the treatment of moderate‐to‐severe palmoplantar psoriasis. Methods: A total of 100 patients with moderate‐to‐severe palmoplantar psoriasis were randomized to either apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of patients who achieved a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) of 0/1 at Week 16. Results: There was no significant difference in the proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients randomized to apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of treatment with apremilast, 24% of patients achieved a PPGA of 0/1. In addition, apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area Severity Index (PPPASI) 75 (apremilast: 22%; placebo: 8%; P = 0.0499), in improving PPPASI (apremilast: −7.4 ± 7.1; placebo: −3.6 ± 5.9; P = 0.0167), Dermatology Life Quality Index score (apremilast: −4.3 ± 5.1; placebo: −0.8 ± 4.5; P = 0.0004) and in reducing activity impairment (apremilast: −11.0 ± 22.3; placebo: 2.5 ± 25.5; P = 0.0063). Conclusion: Despite the absence of a significant difference between apremilast and placebo in proportion of patients achieving a PPPGA of 0/1, the presence of significant differences observed for several secondary endpoints suggests that apremilast may have a role in the treatment of moderate‐to‐severe palmoplantar psoriasis. [ABSTRACT FROM AUTHOR]

Background Patients with moderate-to-severe psoriasis report impaired health-related quality of life ( HRQoL). Objective To assess speed of onset of ixekizumab-induced clinically relevant improvement in HRQoL. Methods This post hoc analysis used pooled data from patients randomized in UNCOVER-2 and UNCOVER-3, and treated with 80 mg ixekizumab every 2 weeks ( IXEQ2W), 80 mg ixekizumab every 4 weeks ( IXEQ4W), 50 mg etanercept ( ETN) twice weekly or placebo ( PBO) for 12 weeks. HRQoL and pruritus were assessed using the Dermatology Life Quality Index ( DLQI) and Itch Numeric Rating Scale ( NRS), respectively. Minimally clinical important differences ( MCID) in DLQI and Itch NRS were defined as ≥5-point and ≥4-point improvements from baseline, respectively. Time to response from randomization was estimated using Kaplan-Meier methodology and the log-rank test. Hazard ratios between treatments were calculated using a Cox proportional hazards regression model adjusting for studies. Results A total of 2570 patients were included: 361 PBO; 740 ETN; 733 IXEQ4W and 736 IXEQ2W. Significantly greater differences in time to DLQI ≥5 point or Itch NRS ≥4 point improvement for IXEQ2W or IXEQ4W compared with ETN and PBO ( P < 0.001) were observed. The median time when 50% of patients reached a ≥5-point reduction in DLQI was shorter for ixekizumab-treated patients (2 weeks, both schedules) compared with ETN- (4 weeks) or PBO-treated (>12 weeks) patients. Likewise, the median time when 50% of patients reached a ≥4-point reduction in Itch NRS was shorter for ixekizumab-treated patients (2 weeks, both schedules) compared with ETN- (8 weeks) or PBO-treated (>12 weeks) patients. Significantly more ixekizumab-treated patients were likely to achieve MCIDs in DLQI or itch reduction compared with ETN or PBO after 12 weeks of treatment. Conclusion Ixekizumab-treated patients achieved more rapid improvements both in HRQoL and itch compared with patients treated with ETN and PBO. [ABSTRACT FROM AUTHOR]