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Background Almost 50% of patients with skin psoriasis have concomitant nail involvement. The comparative effectiveness of the available biologics for nail psoriasis (NP) is still an area of contention because of limited data on nails. Objectives We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics in achieving complete resolution of NP. Methods We identified studies in PubMed, EMBASE and Scopus. The eligibility criteria included randomized controlled trial (RCTs) or cohort studies for psoriasis or psoriatic arthritis with at least two arms of active comparator of biologic reporting at least one efficacy outcome of interest: that is the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI or the Physician's Global Assessment of Fingernail Psoriasis with a score of 0. Results Fourteen studies comprising seven treatments met the inclusion criteria, and were included in the NMA. The NMA showed the odds of complete NP resolution were superior with ixekizumab [risk ratio (RR) 1.4, 95% confidence interval (CI) 0.73–3.10] compared with the treatment of reference (adalimumab). Brodalumab (RR 0.92, 95% CI 0.14–7.40), guselkumab (RR 0.81, 95% CI 0.40–1.80), infliximab (RR 0.90, 95% CI 0.19–4.60) and ustekinumab (RR 0.33, 95% CI 0.08–1.60) demonstrated worse therapeutic effect compared with adalimumab. According to the surface under the cumulative ranking curve, ixekizumab 80 mg every 4 weeks had the highest probability of being the best treatment. Conclusions The interleukin-17A inhibitor ixekizumab has the highest rate of complete nail clearance and it can be considered the best-ranked therapy from the present evidence. This study is relevant to daily practice as it facilitates the decision when choosing between the wide variety of available biologics in patients for whom clearance of nail symptoms is the first concern. [ABSTRACT FROM AUTHOR]

Objective PsA is a chronic disease with heterogeneous clinical manifestations requiring treatment options with long-term efficacy and safety. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. Methods KEEPsAKE 1 is an ongoing, global, phase 3 study with a 24-week, double-blind, placebo-controlled period (period 1) and an open-label extension period (period 2). In period 1, eligible patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16. At week 24 (period 2), all continuing patients received open-label risankizumab 150 mg every 12 weeks through week 208. Results At week 24, 57.3% of risankizumab-treated patients (n  =   483) achieved ≥20% improvement in ACR criteria (ACR20) vs 33.5% of placebo-treated patients (n  =   481; P  < 0.001). At week 52, 70.0% of patients who were randomized to receive continuous risankizumab therapy and 63.0% of patients who were randomized to receive placebo in period 1 and then receive risankizumab at week 24 achieved ACR20. Similar result trends were observed for other efficacy measures. Risankizumab was well tolerated through 52 weeks of treatment with a consistent safety profile from week 24 through week 52. Conclusion In patients with active PsA who were csDMARD-IR, continuous risankizumab treatment demonstrated robust long-term efficacy and was well tolerated through 52 weeks of treatment. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , KEEPsAKE1, NCT03675308. [ABSTRACT FROM AUTHOR]

Objective PsA is a chronic inflammatory disease in which the skin and joints are affected. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or two biologic therapies (Bio-IR) or one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. Methods In the ongoing, phase 3, KEEPsAKE 2 trial, patients with active PsA were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16 (period 1). At week 24 (period 2), patients who received placebo were switched to risankizumab, and all patients received risankizumab 150 mg every 12 weeks from weeks 28 to 208. Results At week 24, 51.3% of risankizumab-treated patients (n  =   224) achieved ≥20% improvement in ACR criteria (ACR 20) vs 26.5% of placebo-treated patients (n  =   220; P  <   0.001). At week 52, 58.5% of patients randomized to receive continuous risankizumab achieved ACR20, and 55.7% of patients who switched from placebo to risankizumab at week 24 achieved ACR20. Similar trends were observed for other efficacy measures. Rates of serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation remained stable through week 52, and no deaths were reported. Conclusion Risankizumab was well tolerated and improved symptoms of PsA in Bio-IR/csDMARD-IR patients, with a consistent long-term safety profile from weeks 24 to 52. Trial registration United States National Library of Medicine clinical trials database www.clinicaltrials.gov ; KEEPsAKE 2; NCT03671148. [ABSTRACT FROM AUTHOR]

Background Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. Objectives To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. Methods We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case–control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. Results We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09–2.40, 95% prediction intervals (PIs) 0.62–4.23, I 2 = 24.90%, τ 2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56–3.25, 95% PI 0.21–24.23, I 2 = 0.00%, τ 2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32–5.07, 95% PI 0.00–3956.27, I 2 = 61.90%, τ 2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33–2.94, I 2 = 0.00%, τ 2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05–1.25, I 2 0.00%, τ 2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents). Conclusions Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear. [ABSTRACT FROM AUTHOR]

Objectives PsA is a heterogeneous disease that impacts many aspects of social and mental life, including quality of life. Risankizumab, an antagonist specific for IL-23, is currently under investigation for the treatment of adults with active PsA. This study evaluated the impact of risankizumab vs placebo on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) among patients with active PsA and inadequate response or intolerance to conventional synthetic DMARD (csDMARD-IR) in the KEEPsAKE 1 trial. Methods Adult patients with active PsA (n  = 964) were randomized (1:1) to receive risankizumab 150 mg or placebo. PROs assessed included the 36-Item Short-Form Health Survey (SF-36, v2), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), EuroQoL-5 Dimension-5 Level (EQ-5D-5L), Patient's Assessment of Pain, Patient's Global Assessment (PtGA) of Disease Activity, and Work Productivity and Activity Impairment–PsA (WPAI-PsA) questionnaire. Least squares (LS) mean change from baseline at week 24 was compared between risankizumab and placebo. Results At week 24, differences between groups were observed using LS mean changes from baseline in SF-36 physical component summary and mental component summary; FACIT-Fatigue; EQ-5D-5L; Patient's Assessment of Pain; PtGA; all eight SF-36 domains (all nominal P  < 0.001); and the WPAI-PsA domains of impairment while working (presenteeism), overall work impairment and activity impairment (all nominal P  < 0.01). Conclusion Risankizumab treatment resulted in greater improvements in HRQoL, fatigue, pain and work productivity in patients with active PsA who have csDMARD-IR, when compared with placebo. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03675308 [ABSTRACT FROM AUTHOR]

Summary: A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)‐23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1‐type disease. Research undertaken from the 1990s to the mid‐2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue‐resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T‐cell recruitment from the blood. Dendritic cells (DCs) are antigen‐presenting cells that contribute to psoriasis pathology via the secretion of IL‐23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL‐36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL‐23‐driven/IL‐17‐producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL‐17 and IL‐23 receptor blockers in the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Objectives Studies have suggested phosphodiesterase 4 (PDE4) inhibition may be associated with weight loss and other cardiometabolic benefits. We evaluated the effect of the PDE4 inhibitor apremilast on body weight and composition, glucose homeostasis, lipid profiles and vascular function in psoriatic disease and whether weight change correlated with therapeutic response. Methods We conducted a prospective, open-label study (Immune Metabolic Associations in Psoriatic Arthritis) of adults receiving apremilast 30 mg as part of routine care for PsA and/or psoriasis. Cardiometabolic, anthropometric and disease activity assessments were performed at baseline (pre-apremilast) and at months 1, 3 and 6 of apremilast treatment in 60 patients. A subgroup underwent further assessment of endothelial function, body composition and adipocyte morphology. Results In patients (median age 54.5 years, 63% women, median BMI 33.2 kg/m2), apremilast was associated with a mean weight loss of 2.2 kg (95% CI 1.4, 3.0; P  < 0.001) and a mean BMI decrease of 0.8 kg/m2 (95% CI 0.5, 1.2; P  < 0.001) after 6 months of treatment. Body composition analysis demonstrated a reduction in total abdominal fat [mean decrease 0.52 L (95% CI 0.08, 0.96), P  = 0.022], principally subcutaneous adipose tissue [mean decrease 0.37 L (95% CI 0.05, 0.68), P  = 0.022]. There was no change in adipocyte diameter, haemoglobin A1c, lipid, glucagon-like peptide-1 or vascular function. Psoriatic disease activity improved with apremilast, although this was not correlated with weight change. Conclusion Following apremilast treatment, we observed weight loss, principally abdominal subcutaneous fat, and improvement in psoriatic disease activity. The latter was independent of weight change, suggesting apremilast likely acts through direct immunological mechanisms. [ABSTRACT FROM AUTHOR]

Summary: Background: Data on treatment exposures for psoriasis and poor COVID‐19 outcomes are limited. Objectives: To assess the risk of hospitalization or in‐hospital mortality due to COVID‐19 by treatment exposure in patients with psoriasis. Methods: All adults with psoriasis registered in the French national health‐insurance (Système National des Données de Santé, SNDS) database between 2008 and 2019 were eligible. Two study periods were considered: 15 February to 30 June 2020 and 1 October 2020 to 31 January 2021, the first and second waves of the COVID‐19 pandemic in France, respectively. Patients were classified according to their baseline treatment: biologics, nonbiologics, topicals or no treatment. The primary endpoint was hospitalization for COVID‐19 using Cox models with inverse probability of treatment weighting. The secondary endpoint was in‐hospital mortality due to COVID‐19. Results: We identified 1 326 312 patients with psoriasis (mean age 59 years; males, 48%). During the first study period, 3871 patients were hospitalized for COVID‐19 and 759 (20%) died; during the second period 3603 were hospitalized for COVID‐19 and 686 (19%) died. In the propensity score‐weighted Cox models, risk of hospitalization for COVID‐19 was associated with exposure to topicals or nonbiologics [hazard ratio (95% confidence interval): 1·11 (1·04–1·20) and 1·27 (1·09–1·48), respectively] during the first period, and with all exposure types, during the second period. None of the exposure types was associated with in‐hospital mortality due to COVID‐19. Conclusions: Systemic treatments for psoriasis (including biologics) were not associated with increased risk of in‐hospital mortality due to COVID‐19. These results support maintaining systemic treatment for psoriasis during the pandemic. Whatis already known about this topic? Almost all chronic diseases have emerged as risk factors for hospitalization for COVID‐19 and poor COVID‐19 outcomes.Multimorbidity is frequent in psoriasis. In France, psoriasis was found to be associated with increased risk of hospitalization for COVID‐19 but not in‐hospital mortality due to COVID‐19.Biologics are associated with an increased risk of infection. Few data have been published on the course of COVID‐19 in patients with psoriasis receiving biologics. Whatdoes this study add? Systemic treatments for psoriasis (including nonbiologics and biologics) were not associated with an increased risk of in‐hospital mortality due to COVID‐19.Our results did not support a prophylactic effect of long‐term use of biologics on risk of hospitalization for COVID‐19 or in‐hospital mortality.These results provide evidence supporting the continuity of care for psoriasis and maintaining systemic treatment for psoriasis during the pandemic. Linked Comment: S. Cazzaniga and L. Naldi. Br J Dermatol 2022; 186:7–8. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long‐term evaluation to assess the durability of their efficacy and safety profiles over time. Objectives: To evaluate the long‐term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. Methods: LIMMitless is an ongoing, phase III, open‐label extension study evaluating the long‐term efficacy and safety of RZB in adults with moderate‐to‐severe plaque psoriasis following multiple phase II/III studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥ 90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90 and PASI 100), static Physician's Global Assessment of clear or almost clear (sPGA 0/1) and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. The study is registered at ClinicalTrials.gov (identifier: NCT03047395). Results: Of 955 patients randomized to RZB 150 mg in the base studies, 897 patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI 90, 54·4% achieved PASI 100, 85·2% achieved sPGA 0/1, and 78·4% achieved DLQI 0/1 using modified nonresponder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long‐term treatment and comparable with those identified in the base studies. Conclusions: Overall, long‐term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks. What is already known about this topic? Risankizumab is a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits interleukin‐23 by binding to its p19 subunit.In multiple phase II/III clinical trials in adults with moderate‐to‐severe psoriasis, risankizumab has displayed superior efficacy vs. placebo or other psoriasis treatments for up to 52 weeks. What does this study add? LIMMitless is an ongoing phase III open‐label extension study designed to evaluate the long‐term safety and efficacy of risankizumab treatment for up to 5 years of continuous use.The results from this interim analysis demonstrate that risankizumab offers sustained efficacy after more than 3 years of continuous use, with no new safety signals identified. Linked Comment: S. Gerdes and J. Albrecht. Br J Dermatol 2021; 185: 1086–1087. [ABSTRACT FROM AUTHOR]

Objectives Biologic treatments have revolutionized the management of PsA by significantly improving clinical manifestations and preventing structural damage. Both result in better quality of life and improved physical functioning. Since the introduction of the first TNF inhibitor (TNFi) in the early 2000s, therapeutic options for PsA are increasing steadily, and a new generation of biologics, including anti-IL-17 and anti-IL-23 strategies, allows distinct targeted approaches. The purpose of this study was to investigate whether the demographic, clinical and disease characteristics of PsA patients who are selected for first-line biologic treatment has changed over time since the introduction of biologics. Methods Patients with a clinical diagnosis of PsA were included in the KU Leuven BioSPAR registry, a prospective cohort of SpA and PsA patients treated with biologics and targeted synthetic DMARDs (tsDMARDs), such as apremilast and Janus kinase inhibitors. Demographics, prior DMARD use, disease characteristics and disease activity parameters were recorded at the initiation of biologic treatment and subsequently every 3 months for the first 2 years and later every 6 months. The patient data were compared in three treatment periods, corresponding to availability of the first and second generation of TNFi and the third generation of biologics. Results Analysis of 185 Caucasian patients with PsA from our prospective cohort showed longer disease duration and higher disease activity, with higher tender joint count, swollen joint count and CRP in the first period compared with the later time periods. The demographic characteristics and prior DMARD use did not change over time. Skin and nail psoriasis were more frequent in earlier compared with the later treatment periods. The bio-DMARD survival rate was similar in the early and later treatment periods. Conclusion The population of patients selected for treatment escalation has changed over time since the introduction of biologics. Our results suggest that with years of experience, PsA patients might be considered earlier and for therapy intensification in patients with less active disease in comparison to profiles in the early days of biologic treatment. [ABSTRACT FROM AUTHOR]

Summary: Background: The phase III reSURFACE 1 and reSURFACE 2 (NCT01722331/NCT01729754) trials of the anti‐interleukin‐23p19 monoclonal antibody tildrakizumab (TIL) for psoriasis treatment are complete. Objectives: We present 5‐year pooled data from reSURFACE 1 and reSURFACE 2. Methods: reSURFACE 1 and reSURFACE 2 were double‐blind, randomized, controlled studies with optional long‐term extensions. Adults with moderate‐to‐severe chronic plaque psoriasis were randomized 2 : 2 : 1 to TIL 100 mg (TIL 100) or 200 mg (TIL 200) or placebo at weeks 0 and 4, and every 12 weeks thereafter [reSURFACE 2 included an etanercept (ETN) arm]. Efficacy outcomes included proportions of patients achieving absolute and relative improvement from baseline Psoriasis Area and Severity Index (PASI) score through week 244 in TIL responders (≥ 75% improvement from baseline PASI; PASI 75 response) continuously receiving the same dose and ETN partial responders and nonresponders (PASI < 75 response) switched to TIL 200 at week 28. Safety was assessed from adverse events (AEs) in all patients as treated. Results: Efficacy analyses included 329 and 227 week 28 responders to TIL 100 and TIL 200, respectively, and 121 ETN partial responders/nonresponders switched to TIL 200 at week 28. Of TIL 100 or TIL 200 responders and ETN partial responders/nonresponders entering the extensions, 235/302, 176/213 and 85/107, respectively, were evaluated at week 244, and 88·7%, 92·5% and 81·3%, respectively, achieved PASI 75 response. Exposure‐adjusted rates of serious AEs were 6·3 and 6·0 patients with events per 100 patient‐years of TIL 100 and TIL 200, respectively. Conclusions: TIL treatment provided sustained disease control over 5 years in week 28 TIL responders and ETN partial responders/nonresponders, with a reassuring safety profile. What's already known about this topic? Tildrakizumab (TIL) is approved for treatment of moderate‐to‐severe psoriasis, and 3‐year data have been previously published.Long‐term efficacy and safety data of biological therapies is crucial to inform clinical practice. What does this study add? TIL is the first anti‐interleukin‐23p19 treatment for which 5‐year efficacy and safety data are reported from two phase III studies, reSURFACE 1 and reSURFACE 2.These data provide evidence of sustained efficacy in TIL responders and in patients switched from etanercept to TIL at week 28, and a favourable long‐term safety profile with total TIL exposure of over 5400 patient‐years. Linked Comment: C.G. Purvis et al. Br J Dermatol 2021; 185:242–243. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time‐dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. Objectives: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. Methods: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. Results: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long‐term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non‐naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). Conclusions: The time‐dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment. What is already known about this topic? Female gender and previous biologic exposure have been discussed as predictors for decreased drug survival in patients with psoriasis, but it remains unknown whether a time‐dependent increased availability of treatment options alters biologic drug survival. What does this study add? The increased availability of alternative biologic treatments over time leads to an elevated risk for treatment discontinuation overall; therefore, drug survival analysis has to be time adjusted.Moreover, the study reveals that the impact of previous biologic treatment on drug survival is tremendous and confirms worse drug survival in female patients. Linked Comment: Gniadecki. Br J Dermatol 2021; 184:996–997. [ABSTRACT FROM AUTHOR]

Summary: Nail involvement is estimated to affect 80–90% of patients with psoriasis at some point in their lives and is often associated with severe disease. Patients with nail involvement experience pain, functional impairment and social stigma, with significant restriction of daily activities and quality of life. Nail psoriasis is also considered a risk factor for the development of psoriatic arthritis (PsA). Management of nail psoriasis is deemed challenging and as a result, it is often left untreated by physicians. Assessing the severity of nail disease can also be difficult in clinical practice. While the Nail Psoriasis Severity Index is used widely in trials, it is time‐consuming and rarely used in the clinic, highlighting the need to develop a simplified disease severity score for nail psoriasis. All patients should be advised to keep their nails short, wear gloves for wet and dirty work, and regularly apply emollient to the nail folds and nail surface. Patients with mild nail psoriasis, without signs of severe cutaneous psoriasis or PsA, may benefit from topical treatment, while systemic treatment is indicated in patients with severe nail involvement. Evidence suggests that all anti‐tumour necrosis factor (TNF)‐α, anti‐interleukin (IL)‐17, and anti‐IL‐12/23 antibodies available for plaque psoriasis and PsA are highly effective treatments for nail psoriasis. This article aims to provide an up‐to‐date review of the therapeutic options currently available for the management of nail psoriasis in patients with or without skin psoriasis. Therapeutic options for the management of nail psoriasis in children will also be discussed. [ABSTRACT FROM AUTHOR]

Objectives TNF inhibitors (TNFis) and IL inhibitors are effective treatments for PsA. Treatment non-persistence (drug survival, discontinuation) is a measure of effectiveness, tolerability and patient satisfaction or preferences in real-world clinical practice. Persistence on these treatments is not well understood in European PsA populations. The aim of this study was to compare time to non-persistence for either ustekinumab (IL-12/23 inhibitor) or secukinumab (IL-17 inhibitor) to a reference group of adalimumab (TNFi) treatment exposures in PsA patients and identify risk factors for non-persistence. Methods A total of 4649 exposures of adalimumab, ustekinumab, and secukinumab in 3918 PsA patients were identified in Swedish longitudinal population-based registry data. Kaplan–Meier curves were constructed to measure treatment-specific real-world risk of non-persistence and adjusted Cox proportional hazards models were estimated to identify risk factors associated with non-persistence. Results Ustekinumab was associated with a lower risk of non-persistence relative to adalimumab in biologic-naïve [hazard ratio (HR) 0.48 (95% CI 0.33, 0.69)] and biologic-experienced patients [HR 0.65 (95% CI 0.56, 0.76)], while secukinumab was associated with a lower risk in biologic-naïve patients [HR 0.65 (95% CI 0.49, 0.86)] but a higher risk of non-persistence in biologic-experienced patients [HR 1.20 (95% CI 1.03, 1.40)]. Biologic non-persistence was also associated with female sex, axial involvement, recent disease onset, biologic treatment experience and no psoriasis. Conclusion Ustekinumab exhibits a favourable treatment persistency profile relative to adalimumab overall and across lines of treatment. The performance of secukinumab is dependent on biologic experience. Persistence and risk factors for non-persistence should be accounted for when determining an optimal treatment plan for patients. [ABSTRACT FROM AUTHOR]

Objectives Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL–10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells. Methods Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured. Results Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells. Conclusion These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells. [ABSTRACT FROM AUTHOR]

Summary: Background: Long‐term therapy for psoriasis is impaired by gradual loss of effectiveness and treatment discontinuation. Identifying factors that affect biologic drug survival may help in treatment optimization. Objectives: To identify factors that predicted biologic drug persistence or discontinuation in a real‐life setting. Methods: We identified studies of biologic persistence in psoriasis through a comprehensive, systematic literature search using predefined search criteria. Studies were screened by title and abstract then further by full‐text review. Hazard ratio (HR) data were extracted for all available predictive factors (HRs > 1 denoted biologic discontinuation, and HRs < 1 denoted biologic persistence). A meta‐analysis of HRs (random‐effects model) was used to assess any predictive factor included in at least two studies. Results: Sixteen cohort studies were included in the review, with a total of 32 194 patients. A meta‐analysis was performed on 13 studies (n = 29 802): nine for female sex (n = 28 090), six for obesity (n = 9311) and six for psoriatic arthritis (n = 24 444). Obesity and female sex predicted treatment discontinuation, with HRs of 1.21 [95% confidence interval (CI) 1.10–1.32, I2 = 0%] and 1.22 (95% CI 1.07–1.38, I2 = 84%), respectively. Concomitant psoriatic arthritis predicted biologic persistence (HR 0.83, 95% CI 0.80–0.86, I2 = 0%). Female sex predicted biologic discontinuation due to side‐effects, with a pooled HR of 2.16 (95% CI 1.39–3.35, I2 = 67%). Other reported predictive factors (smoking, metabolic syndrome, biologic naivety, age, Dermatology Life Quality Index, dyslipidaemia, high socioeconomic status and concomitant methotrexate) were insufficiently reported for meta‐analysis. Conclusions: Our meta‐analysis demonstrates that female sex and obesity predict biologic discontinuation, and concomitant psoriatic arthritis predicts biologic survival. What's already known about this topic? Ineffectiveness is the main factor that causes drug discontinuation during long‐term treatment of psoriasis.It is unclear which factors and comorbidities impact drug persistence. What does this study add?Female sex and obesity predict biologic discontinuation due to ineffectiveness and adverse events.Concomitant psoriatic arthritis is associated with improved drug persistence. Linked Comment: van den Reek. Br J Dermatol 2019; 181:438. [ABSTRACT FROM AUTHOR]

Lipid mediators, such as prostanoids and leukotrienes (LTs), exert a range of actions through their own receptors on cell surfaces in various pathophysiological conditions. It has been reported that the production of prostanoids and LTs is significantly elevated in the skin lesions of some chronic inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis, showing the possible involvement of these lipid mediators in the development of those diseases. Although the actual significance of these lipid mediators in humans is still unclear, the findings from studies in mice suggest diverse roles of the lipid mediators in the progression or regulation of these diseases. For example, in a mouse AD model, prostaglandin D2 inhibits the induction of Th2 cells through DP receptor on Langerhans cells, while it promotes infiltration of Th2 cells through chemoattractant receptor-homologous molecule expressed on Th2 cells. In a psoriasis model, thromboxane A2-TP signaling promotes psoriatic dermatitis by facilitating IL-17 production from γδ T cells. In this short review, we summarize the current findings on the roles of prostanoids and LTs in AD and psoriasis as revealed by studies in mice, and discuss the potential of these lipid mediators as therapeutic targets in humans. [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated the use of optical coherence tomography (OCT) imaging as a biomarker response to treatment for nail disease in psoriasis and psoriatic arthritis. The study covered four patients using the Nail Psoriasis Severity Index as outcome measures. Results showed that OCT identifies all common psoriasis nail changes and the findings suggest that OCT imaging may be a useful tool for assessing nail biomarker in psoriasis.

Summary: Background: Real‐life data on newer biological and biosimilar agents for moderate‐to‐severe psoriasis are lacking. Objectives: To examine safety, efficacy and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab and ustekinumab) and compare originators with biosimilars (i.e. Enbrel with Benepali, and Remicade with Remsima). Methods: The DERMBIO registry contains data on all Danish patients with moderate‐to‐severe plaque psoriasis treated with biologics. We examined patients treated between 1 January 2007 and 31 March 2017. We used Kaplan–Meier survival curves and Cox regression to examine drug survival patterns. Results: A total of 3495 treatment series (2161 patients) were included (adalimumab n = 1332; etanercept n = 579; infliximab n = 333; ustekinumab n = 1055 and secukinumab n = 196). Secukinumab had the highest number of PASI 100 (100% improvement from baseline Psoriasis Area and Severity Index) respondents, but also the lowest drug survival among all the biologics. Ustekinumab had the highest drug survival overall. There were no significant differences in discontinuation risk between originator and biosimilar versions of infliximab or etanercept. Treatment with higher than approved dosages was frequent for all drugs except for adalimumab and secukinumab. Adverse events (predominantly infections) were most frequent for secukinumab compared with the other agents. Conclusions: Ustekinumab was associated with the highest drug survival, and secukinumab with the lowest, although most patients on secukinumab were non‐naïve. Switching from originator to biosimilar had no significant impact on drug survival, and the safety profiles were comparable. Adverse events occurred most frequently with secukinumab. Future studies are warranted to assess the long‐term safety of novel biologics for psoriasis. [ABSTRACT FROM AUTHOR]

The last two decades have seen a rapid growth of targeted biologic therapies for moderate-to-severe plaque psoriasis. The study participants in each treatment arm had similar baseline characteristics, including demographics, psoriasis duration and prior psoriasis therapies, which indicate a robust randomization process and minimal selection bias. Nevertheless, the ECLIPSE study provides important new information to guide longer-term therapy choices among the newer biologic treatment options for psoriasis, and highlights the importance of and need for comparative studies of longer duration. [Extracted from the article]