Remission in Type 2 Inflammatory Diseases: Current Evidence, Unmet Needs, and Suggestions for Defining Remission in Chronic Rhinosinusitis with Nasal Polyps.

PURPOSE OF REVIEW: The development of biological therapies for type 2 inflammatory diseases raises the possibility of addressing remission in those dis-immune conditions. No consensus exists for a definition of remission in chronic rhinosinusitis with nasal polyps (CRSwNP). This review aims to critically evaluate the published data to provide the basis for defining remission in CRSwNP. RECENT FINDINGS: The published evidence has yet to provide an unequivocal definition on remission in type 2 inflammatory diseases, in part reflecting differences in approaches to diagnosis and follow-up. A multidimensional evaluation is necessary when considering complete remission, including clinical, inflammatory, and histologic criteria, but how to combine or tailor the three perspectives according to disease severity at baseline or timing of assessment of treatment category is yet to reach consensus. We suggest defining remission starting from the approach taken in asthma and eosinophilic esophagitis, that is, including the resolution of symptoms and improvements in objective parameters of disease severity and/or inflammatory activity. Future studies and consensuses should provide validated criteria with cutoffs for the day-to-day definition of remission. The definition of remission in CRSwNP should include the following criteria, to be verified and maintained for a period of ≥ 12 months: absence of symptoms (nasal obstruction, loss of smell, rhinorrhea as the main ones); no impact of symptoms on quality of life; no need of surgery; no chronic or rescue medications (systemic corticosteroids or antibiotics); and recovery of smell function, possibly evaluated by objective test. Assessment of underlying inflammation should also be considered once accurate and feasible biomarkers are available in clinical practice.

Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over 2 years in randomized phase 3/3b trials.

BACKGROUND: Patients with psoriasis are at increased risk of liver function abnormalities. OBJECTIVE: Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis. METHODS: Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY). RESULTS: 2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline. LIMITATIONS: Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction. CONCLUSION: Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods.

Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

EULAR points to consider for the definition of clinical and imaging features suspicious for progression from psoriasis to psoriatic arthritis.

BACKGROUND: The transition from psoriasis (PsO) to psoriatic arthritis (PsA) and the early diagnosis of PsA is of considerable scientific and clinical interest for the prevention and interception of PsA. OBJECTIVE: To formulate EULAR points to consider (PtC) for the development of data-driven guidance and consensus for clinical trials and clinical practice in the field of prevention or interception of PsA and for clinical management of people with PsO at risk for PsA development. METHODS: A multidisciplinary EULAR task force of 30 members from 13 European countries was established, and the EULAR standardised operating procedures for development for PtC were followed. Two systematic literature reviews were conducted to support the task force in formulating the PtC. Furthermore, the task force proposed nomenclature for the stages before PsA, through a nominal group process to be used in clinical trials. RESULTS: Nomenclature for the stages preceding PsA onset, 5 overarching principles and 10 PtC were formulated. Nomenclature was proposed for three stages towards PsA development, namely people with PsO at higher risk of PsA, subclinical PsA and clinical PsA. The latter stage was defined as PsO and associated synovitis and it could be used as an outcome measure for clinical trials evaluating the transition from PsO to PsA. The overarching principles address the nature of PsA at its onset and underline the importance of collaboration of rheumatologists and dermatologists for strategies for prevention/interception of PsA. The 10 PtC highlight arthralgia and imaging abnormalities as key elements of subclinical PsA that can be used as potential short-term predictors of PsA development and useful items to design clinical trials for PsA interception. Traditional risk factors for PsA development (ie, PsO severity, obesity and nail involvement) may represent more long-term disease predictors and be less robust for short-term trials concerning the transition from PsO to PsA. CONCLUSION: These PtC are helpful to define the clinical and imaging features of people with PsO suspicious to progress to PsA. This information will be helpful for identification of those who could benefit from a therapeutic intervention to attenuate, delay or prevent PsA development.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

BACKGROUND: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic. OBJECTIVES: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence. METHODS: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence. RESULTS: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49). CONCLUSIONS: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.

Optimization of long-range PCR protocol to prepare filaggrin exon 3 libraries for PacBio long-read sequencing.

BACKGROUND: The filaggrin (FLG) protein, encoded by the FLG gene, is an intermediate filament-associated protein that plays a crucial role in the terminal stages of human epidermal differentiation. Loss-of-function mutations in the FLG exon 3 have been associated with skin diseases. The identification of causative mutations is challenging, due to the high sequence homology within its exon 3 (12,753 bp), which includes 10 to 12 filaggrin tandem repeats. With this study we aimed to obtain the whole FLG exon 3 sequence through PacBio technology, once 13-kb amplicons have been generated. METHODS AND RESULTS: For the preparation of SMRTbell libraries to be sequenced using PacBio technology, we focused on optimizing a 2-step long-range PCR protocol to generate 13-kb amplicons covering the whole FLG exon 3 sequence. The performance of three long-range DNA polymerases was assessed in an attempt to improve the PCR conditions required for the enzymes to function properly. We focused on optimization of the input template DNA concentration and thermocycling parameters to correctly amplify the entire FLG exon 3 sequence, minimizing non-specific amplification. CONCLUSIONS: Taken together, our findings suggested that the PrimeSTAR protocol is suitable for producing the amplicons of the 13-kb FLG whole exon 3 to prepare SMRTbell libraries. We suggest that sequencing the generated amplicons may be useful for identifying LoF variants that are causative of the patients' disorders.

Atopic Dermatitis in the Elderly Population.

Atopic dermatitis is a common inflammatory disease with a chronic and relapsing course. Although considered a childhood disease, it is now evident that atopic dermatitis is also common in adulthood and in the elderly population. Atopic dermatitis typically manifests with bilateral and symmetrical eczematous lesions on the face, trunk and skin folds. Itch is invariably present and may be very severe, markedly  affecting daily life and sleep. In older adults, atopic dermatitis may have a high level of impact on quality of life, frequently burdening an already complex comorbid situation. The full assessment of disease burden (localizations, itch severity, sleep alterations, impact on quality of life, disease history, comorbidities) is crucial to identify the most appropriate treatment. In many cases, moderate-to-severe atopic dermatitis in the elderly population can be successfully and safely treated with biological agents inhibiting the interleukin-4/-13 pathway, whereas the use of Janus kinase inhibitors may pose concerns about the safety profile.

Efficacy and safety of apremilast in patients with limited skin involvement, plaque psoriasis in special areas and impaired quality of life: Results from the EMBRACE randomized trial.

INTRODUCTION/BACKGROUND: Manifestations of psoriasis in special areas are difficult to treat and are associated with a high disease burden and significant quality of life (QoL) impairment. Topical therapies may be inadequate for these patients, necessitating systemic treatment. OBJECTIVE: The objective of EMBRACE was to evaluate the impact on QoL, efficacy and safety of apremilast 30 mg BID in patients with limited skin involvement with plaque psoriasis manifestations in special areas and impaired QoL. METHODS: EMBRACE (NCT03774875) was a phase 4, randomized, placebo-controlled, multinational study. Patients had plaque psoriasis not controlled by topical therapy; lack of response, contraindication or intolerance to conventional first-line systemic therapy; psoriasis in ≥1 special area (including visible locations, scalp, nails, genital areas or palmoplantar areas); Psoriasis Area and Severity Index (PASI) ≥3 to ≤10; and Dermatology Life Quality Index (DLQI) >10. The primary endpoint was DLQI response (≥4-point reduction) at Week 16. RESULTS: Of 277 randomized patients (apremilast: n = 185; placebo: n = 92), 221 completed Week 16 (apremilast: n = 152; placebo: n = 69). The primary endpoint (≥4-point reduction in DLQI at Week 16) was met by significantly more patients receiving apremilast (73.3%) versus placebo (41.3%; p < 0.0001). Significantly greater improvement in affected body surface area (BSA) and PASI was observed with apremilast versus placebo at Week 16. There were also significantly greater improvements with apremilast versus placebo in itch numeric rating scale (-2.5 vs. -0.9, p < 0.0001) and skin discomfort/pain visual analog scale (-21.5 vs. -5.4, p = 0.0003) and greater achievement of Patient Benefit Index ≥1 (77% vs. 40%, p < 0.0001) at Week 16. No new safety signals were observed. CONCLUSIONS: Apremilast significantly improved skin-related QoL in patients with limited skin involvement with plaque psoriasis in special areas and highly impaired QoL. The safety profile was consistent with prior apremilast studies.

Quality of life and stigmatization in people with skin diseases in Europe: A large survey from the 'burden of skin diseases' EADV project.

BACKGROUND: Several large studies on the burden of skin diseases have been performed in patients recruited in hospitals or clinical centres, thus missing people with skin diseases who do not undergo a clinical consultation. OBJECTIVES: To evaluate the burden of the most common dermatological diseases in adult patients across Europe, in terms of quality of life, work life, and stigmatization. METHODS: Population-based survey on a representative sample of the European general population aged 18 years or older. Participants who declared to have had one or more skin problem or disease during the previous 12 months completed the Dermatology Life Quality Index questionnaire, and answered questions regarding the impact of their skin disease on daily and work life, anxiety/depression, and stigmatization. RESULTS: The study population included 19,915 individuals, 44.7% of whom were men. Quality of life was particularly impaired in people with hidradenitis suppurativa (HS), and sexually transmitted diseases. About a half of participants with acne, alopecia, or chronic urticaria, and about 40% of those with atopic dermatitis (AD), skin cancers, or psoriasis reported a modest to extremely large effect of the disease on their quality of life. Overall, 88.1% of participants considered their skin disease as embarrassing in personal life and 83% in work life. About half of the respondents reported sleeping difficulty, feeling tired, and impact of the disease on taking care of themselves. Concerning stigmatization, 14.5% felt to have been rejected by others because of the skin disease, and 19.2% to have been looked at with disgust. Anxiety and depression were frequently reported by patients with all the diseases. CONCLUSIONS: Skin diseases may heavily affect patients' daily and work life, and cause feelings of stigmatization. An early intervention is needed to avoid consequences on the patients' life course.

Public perception of dermatologists in Europe: Results from a population-based survey.

BACKGROUND: The public perception of dermatology has been poorly investigated in Europe. OBJECTIVE: To determine the general public's perception of dermatologists in Europe. METHODS: This multinational, cross-sectional study was conducted within the framework of the EADV population-based survey on the 'Burden of skin diseases in Europe'. Data were collected using a web-based online survey on a representative sample of the general populations aged 18 years or more of 27 European countries. Proportional quota sampling with replacement design was used for each country. RESULTS: A total of 44,689 adult participants responded to the questionnaire, of whom 18,004 visited a dermatologist in the preceding 3 years. The dermatologist was the second most often visited specialist among all medical specialties, with 69.7%, 72.1%, 42.1% and 78.1% of participants in Western Europe (WE), Eastern Europe (EE), Northern Europe (NE) and Southern Europe (SE), respectively, having consulted a dermatologist over the past 24 months. Most participants across all regions agreed that the dermatologist was the first healthcare provider for chronic skin diseases (61.9% in WE, 69.8% in EE, 45.7% in NE and 60.4% in SE) and for skin cancers (65.5% in WE, 67.6% in EE, 42.4% in NE and 63.0% in SE). The five most common reasons for visiting a dermatologist among all participants were: naevi check-up or skin cancer screening (20.2%), chronic skin diseases (16.5%), acute skin diseases (12.4%), cosmetic advice or procedure (10.2%), hyperpigmentation or congenital lesions (9.1%) and hair or nail disorder (7.7%). Most participants (84.6% in WE, 82.5% in EE, 78.3% in NE and 82.8% in SE) were very swatisfied/somewhat satisfied with the service provided. CONCLUSION: Our study findings underscore the central role of dermatologists in skin health and highlights them as valued and trusted care providers across Europe. Understanding the perceived position of the dermatologist is the first step in improving health policy development and implementation. Notably, access to a dermatologist was lowest in NE, probably reflecting differences in healthcare organizational structures or possibly cultural differences in healthcare seeking behaviour.

The journey of patients with skin diseases from the first consultation to the diagnosis in a representative sample of the European general population from the EADV burden of skin diseases study.

BACKGROUND: The journey of patients with skin diseases through healthcare has been scarcely investigated. OBJECTIVE: To analyse the journey of people with skin diseases in the different healthcare environment in Europe. METHODS: This multinational, cross-sectional, European study was conducted on a representative sample of the adult general population of 27 European countries. The prevalence of the most frequent skin diseases was determined. Information was collected on the patient journey from the first medical consultation to the diagnosis, and the reasons for not consulting a healthcare professional. RESULTS: On a total of 44,689 individuals, 30.3% reported to have consulted a dermatologist during the previous 2 years. Participants consulted mainly for mole control or skin cancer screening (22.3%), followed by chronic skin diseases (16.2%). The diagnoses of acne, atopic dermatitis, psoriasis and rosacea were made most frequently by a dermatologist, while fungal skin infections were diagnosed more often by a general practitioner (GP), and sexually transmitted diseases (STD) by other specialists. The diagnosis was not always definitive at the first consultation, in particular for STD. The percentage of people who did not consult a healthcare professional for their skin disease was particularly high for acne (36.4%), alopecia (44.7%) and fungal infection (30.0%). Moreover, 17.7% of respondents with psoriasis did not consult. A high percentage of participants with alopecia thought that the disease was not worrying, while patients with psoriasis often answered that they were able to manage the disease since they had already consulted a doctor. Many patients with acne (41.1%) and fungal infection (48.2%) thought that they were able to handle the disease by themselves. CONCLUSION: The analysis of the self-reported medical journey of patients with common skin diseases may allow to understand the unmet needs of patients, thus improving outcomes and reducing expenses.

Biological disease-modifying antirheumatic drugs may mitigate the risk of psoriatic arthritis in patients with chronic plaque psoriasis.

OBJECTIVE: To estimate the incidence of psoriatic arthritis (PsA) in patients with psoriasis who had received a continuous treatment with biological disease-modifying antirheumatic drugs (bDMARDs) compared with phototherapy. METHODS: A retrospective non-randomised study involving patients with moderate-to-severe plaque psoriasis, who were prescribed at least 5 years of bDMARDs or at least three narrow-band ultraviolet light B (nb-UVB) phototherapy courses, and did not have a diagnosis of PsA at enrolment. Development of PsA in each patient was assessed by a rheumatologist according to the Classification for Psoriatic Arthritis criteria. The annual and cumulative incidence rate of PsA was estimated by using an event per person-years analysis. Cox proportional hazards models were undertaken to assess the hazard risk (HR) of PsA after adjustment for confounders. RESULTS: A total of 464 psoriatic patients (bDMARDs, n=234 and nb-UVB, n=230) were followed between January 2012 and September 2020 (corresponding to 1584 and 1478 person year of follow-up for the two groups, respectively). The annual incidence rate of PsA was 1.20 cases (95% CI 0.77 to 1.89) versus 2.17 cases (95% CI 1.53 to 3.06) per 100 patients/year in the bDMARDs versus phototherapy group, respectively (HR 0.29, 0.12-0.70; p=0.006). The variables independently associated with higher risk of PsA were older age (adjusted HR 1.04, 1.02-1.07), nail psoriasis (adjusted HR 3.15, 1.63-6.06) and psoriasis duration >10 years (adjusted HR 2.02, 1.09-3.76); notably, bDMARDs treatment was associated with a lower risk of incident PsA (adjusted HR 0.27, 0.11-0.66). CONCLUSIONS: bDMARDs treatment may delay or reduce the risk of incident PsA in patients with moderate-to-severe chronic plaque psoriasis.

Risk of lymphohematologic malignancies in patients with chronic plaque psoriasis: A systematic review with meta-analysis.

BACKGROUND: The association between chronic plaque psoriasis and lymphohematologic malignancies (LHMs) remains controversial. OBJECTIVE: To investigate the risk of LHMs in patients with psoriasis according to the best evidence. METHODS: A systematic review and meta-analysis of observational cohort studies was undertaken to assess the association of psoriasis with different LHMs. A literature search for relevant studies was performed on February 28, 2021. The random-effects model in conducting meta-analyses was applied. To evaluate the risk of bias, the Newcastle-Ottawa Scale was employed. RESULTS: A total of 25 observational studies were selected, comprising collectively 2,501,652 subjects. A significantly increased risk for LHM (hazard ratio [HR], 1.55; 1.24-2.94) and lymphoma (HR, 1.27; 1.08-1.50) in patients with moderate-to-severe plaque psoriasis compared to the general population was found. In detail, increased risks for Hodgkin lymphoma (HR, 1.71; 1.27-2.30), non-Hodgkin lymphoma (HR, 1.27; 1.08-1.50), multiple myeloma (HR, 1.32; 1.03-1.69), and leukemia (HR, 1.28; 1.00-1.65) were found. The risk of cutaneous T-cell lymphoma was markedly augmented in patients with psoriasis (HR, 6.22; 3.39-11.42). LIMITATIONS: Possible ascertainment bias related to the diagnosis of LHMs. CONCLUSION: The increased risk of LHMs, particularly cutaneous T-cell lymphoma, in patients with psoriasis could be related to exposure to systemic immunosuppressive therapies, comorbidities, and sustained immune activation, particularly in the skin.

Hypochondriasis and Personality Traits of Patients with Chronic Plaque Psoriasis.

BACKGROUND: Plaque psoriasis has been associated with anxiety, depression, suicidal ideation and various personality traits. However, studies on hypochondriasis, i.e. the belief of serious illness despite having no or only mild symptoms, are currently scarce. OBJECTIVE: The aim of this study was to assess hypochondriasis and personality traits in psoriasis patients using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). METHODS: We conducted an observational study on patients with plaque psoriasis who underwent MMPI-2 testing. Demographic and clinical data, including comorbidities, alcohol consumption, and smoking, were collected. RESULTS: A total of 136 consecutive psoriatic patients were included. The mean age (±SD) was 53.7 (±13.5), mean PASI (Psoriasis Area Severity Index) was 12.4 (±9.9), and mean disease duration was 23.3 (±15.7) years. Pathologically elevated scores in the Hypochondriasis scale were observed in 27.9% of patients. Furthermore, in a few other MMPI-2 scales (Anxiety, Fears and Negative Treatment Indicators) ≥25% of patients obtained pathologically elevated scores. Conversely, the scales that had the highest proportion of low scorers were Ego Strength and Dominance. At regression analysis, higher psoriasis severity and female gender were associated with higher scores in the Hypochondriasis scale (p = 0.03 and 0.001). Finally, 72.8% reported any alcohol consumption and 8.1% heavy alcohol consumption. CONCLUSION: About one third of patients with psoriasis have high scores in the MMPI-2 hypochondriasis evaluation scale. Poor individual coping resources also appeared to be distinctive psychological features in a significant proportion of psoriatic patients.

Non-Alcoholic Fatty Liver Disease Is Associated With Reduced Glomerular Filtration Rate in Patients With Chronic Plaque Psoriasis.

BACKGROUND: Chronic plaque psoriasis has been associated with metabolic comorbidities, including non-alcoholic fatty liver disease (NAFLD). A causal relationship between NAFLD and chronic kidney disease (CKD) is debated. OBJECTIVES: To assess whether NAFLD is associated with impaired renal function in patients with psoriasis. METHODS: A multicenter, retrospective, observational study including 337 patients with moderate-to-severe chronic plaque psoriasis, who had no history of excessive alcohol consumption or other secondary causes of chronic liver and renal diseases was conducted. NAFLD was diagnosed by ultrasonography, and CKD stage ≥2 or stage ≥3 were defined by an estimated glomerular filtration rate (e-GFR) of <90 ml min-1 1.73 m-2 or <60 ml min-1 1.73 m-2, respectively. Logistic and linear regression analyses were undertaken to assess the independent association of NAFLD with CKD or eGFR levels. RESULTS: Patients with NAFLD (n = 212, 62.9% of total) had significantly lower e-GFR levels (83.4 ± 18.0 vs. 93.5 ± 15.8 ml min-1 1.73 m-2, P<.001) and a remarkably higher prevalence of both CKD stage ≥2 (56.1% vs. 30.4%, P<.0001) and CKD stage ≥3 (10.4% vs. 3.2%, P<.0001) compared with their counterparts without NAFLD. Multivariable logistic regression analysis showed that NAFLD was associated with a nearly 2.5-fold increased risk of prevalent CKD stage ≥2 (adjusted-odds ratio= 2.60 95% confidence intervals 1.4-4.8, P=.02), independently of components of metabolic syndrome, psoriasis severity, and psoriatic arthritis. CONCLUSIONS: Ultrasound-diagnosed NAFLD is strongly associated with a reduced eGFR in patients with moderate-to-severe psoriasis, independently of cardiometabolic risk factors and psoriasis-related variables.

Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: A Northern Italy experience.

INTRODUCTION: Whether biologic therapies enhance the risk of coronavirus 2019 (COVID-19) or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained. OBJECTIVE: We sought to investigate the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. METHODS: This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n = 6501) being treated with biologic therapy and regularly followed up at the divisions of dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates of hospitalization and death per 10,000 person-months with exact mid-p 95% CIs and standardized incidence ratios were estimated in the patients with psoriasis and compared with those in the general population in the same geographic areas. RESULTS: The incidence rate of hospitalization for COVID-19 was 11.7 (95% CI, 7.2-18.1) per 10,000 person-months in patients with psoriasis and 14.4 (95% CI, 14.3-14.5) in the general population; the incidence rate of death from COVID-19 was 1.3 (95% CI, 0.2-4.3) and 4.7 (95% CI, 4.6-4.7) in patients with psoriasis and the general population, respectively. The standardized incidence ratio of hospitalization and death in patients with psoriasis compared with those in the general population was 0.94 (95% CI, 0.57-1.45; P = .82) and 0.42 (95% CI, 0.07-1.38; P = .19), respectively. CONCLUSIONS: Our data did not show any adverse impact of biologics on COVID-19 outcome in patients with psoriasis. We would not advise biologic discontinuation in patients on treatment since more than 6 months and not infected with severe acute respiratory syndrome coronavirus 2 to prevent hospitalization and death from COVID-19.

Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.

BACKGROUND: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited. OBJECTIVE: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization. METHODS: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors. RESULTS: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94). CONCLUSION: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.

Could Targeted Pharmacotherapies Exert a "Disease Modification Effect" in Patients with Chronic Plaque Psoriasis?

Chronic plaque psoriasis is an immune-mediated skin disease with a chronic relapsing course, affecting up to ~2-3% of the general adult population worldwide. The interleukin (IL)-23/Th17 axis plays a key role in the pathogenesis of this skin disease and may represent a critical target for new targeted pharmacotherapies. Cutaneous lesions tend to recur in the same body areas, likely because of the reactivation of tissue-resident memory T cells. The spillover of different pro-inflammatory cytokines into systemic circulation can promote the onset of different comorbidities, including psoriatic arthritis. New targeted pharmacotherapies may lead to almost complete skin clearance and significant improvements in the patient's quality of life. Accumulating evidence supports the notion that early intervention with targeted pharmacotherapies could beneficially affect the clinical course of psoriatic disease at three different levels: (1) influencing the immune cells infiltrating the skin and gene expression, (2) the prevention of psoriasis-related comorbidities, especially psoriatic arthritis, and (3) the improvement of the patient's quality of life and reduction of cumulative life course impairment. The main aim of this narrative review is to summarize the effects that new targeted pharmacotherapies for psoriasis may have on the immune scar, both at the molecular and cellular level, on psoriatic arthritis and on the patient's quality of life.

The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events.

Hydroxychloroquine is an established therapy for several rheumatological disorders, and very recently it has been proposed as a possible treatment for the new coronavirus disease 2019 even if recent randomised trials did not prove any benefit. Notably, hydroxychloroquine has been associated with a heterogeneous range of cutaneous and extra-cutaneous adverse events. We carried out a narrative review of the literature up to November 1st, 2020, related to the safety of hydroxychloroquine. In particular, cutaneous and extra-cutaneous adverse events associated with hydroxychloroquine were reviewed. The following databases were consulted: PubMed, Embase, Google Scholar and ResearchGate. The research of articles was conducted by using the following search terms: ''hydroxychloroquine," ''adverse event/effect,'' "cutaneous", "skin", "cardiotoxicity", "retinopathy", gastrointestinal and neurological toxicity". The main indication for which hydroxychloroquine was used in the reports was an immune mediated disorder. Adverse events were described mostly in females over 50 years of age. The most common cutaneous adverse effect was maculopapular and erythematous rash occurring within 4 weeks of initiating hydroxychloroquine and disappearing within few weeks of discontinuation. Gastrointestinal symptoms and headache were the most frequent extracutaneous manifestations. Rarer cutaneous manifestations include hyperpigmentation, psoriasiform dermatitis, photodermatitis, stomatitis, melanonychia and hair loss. More severe conditions were acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, and among extra-cutaneous adverse events cardiotoxicity and retinopathy. Since hydroxychloroquine is widely prescribed in rheumatology, it is important for rheumatologists to be familiar with its safety profile.

Comparative safety and benefit-risk profile of biologics and oral treatment for moderate-to-severe plaque psoriasis: A network meta-analysis of clinical trial data.

BACKGROUND: The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatment have not been well studied. OBJECTIVE: To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments. METHODS: A systematic literature review of phase II-IV randomized controlled trials of moderate-to-severe psoriasis treatments was conducted (cutoff: July 1, 2020). Any adverse events (AEs), any serious AEs, and AEs leading to treatment discontinuation were compared using Bayesian network meta-analyses (NMAs). RESULTS: Fifty-two and 7, respectively, randomized controlled trials were included in the short- and long-term NMAs, respectively. In the short-term NMA, the rates of any AEs were the lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any serious AE were the lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were the lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long-term NMA, risankizumab had the lowest rates of all 3 outcomes (67.5%, 4.4%, and 1.0%, respectively) and the most favorable benefit-risk profile. LIMITATIONS: The results may not be generalizable to real-world populations. CONCLUSIONS: Anti-interleukin 23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term.