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Purpose of Review SARS-CoV-2 has had a devastating global effect, with vaccinations being paramount in the public health strategy against COVID-19. Vaccinations have uncoupled infection from adverse COVID-19 outcomes worldwide. While immune-modifying therapies are effective for the management of skin diseases such as psoriasis and atopic dermatitis, these medications also impair protective immune responses. There has been longstanding uncertainty and concern over the impact of immune-modifying therapies on the effectiveness of vaccines; for example, it is well recognised that methotrexate impairs humoral responses to both influenza and pneumococcal vaccines. This narrative review aims to discuss the evidence to date on the impact of immune-modifying therapies on the immune response to COVID-19 vaccines, with a focus on the first two vaccine doses. Recent Findings Individuals receiving immune-modifying therapy are more likely to have attenuated humoral responses to a single dose of COVID-19 vaccine compared to healthy controls; however, this may be improved by a complete course of vaccination. B cell targeted biologics such as rituximab markedly impair the humoral response to both the first and second COVID-19 vaccination. There remains a paucity of data on cellular immune responses, with the few available studies indicating lower responses to two vaccine doses in individuals receiving immune-modifying therapies compared to healthy controls, which may impact the durability of immune responses. Summary Inadequate humoral immune responses to a single dose of vaccine in the context of immune-modifying therapy are improved by a complete course of vaccination. Individuals receiving immune-modifying treatments should be encouraged to take up a complete vaccine course to mitigate their risk against COVID-19. Research in large patient populations on the longevity/kinetics of the complex humoral and cellular response to subsequent vaccine doses, including against newer variants of concern, is warranted, in addition to data on immune correlates of vaccine clinical effectiveness.

In this cross sectional study from a large UK centre, screening for mental illness in individuals with psoriasis has demonstrated a high burden of depression and anxiety. 85% of the cohort report that their psoriasis had affected their quality of life. Quality of life scores correlate with depression scores, emphasing the importance of managing individual's mental health alongside their psoriasis to improve overall quality of life.

We carried out a critical appraisal of the literature to assess whether Janus kinase inhibitors are an effective treatment for palmoplantar pustulosis, a rare and debilitating form of psoraisis. Our appraisal identified case reports and case series of 16 patients who have been treated to good effect with tofacitinib, indicating this may be a promising therapeutic option. However, routine use of janus kinase inhibitors cannot be recommended outside the context of a clinical trial given the current low-quality of evidence available and the uncertain safety profile of Janus kinase inhibitors.

Background Tumour necrosis factor-alpha inhibitors (TNFi) have revolutionized the treatment of moderate-to-severe psoriasis. Following patent expiry of the originator biologics, TNFi biosimilars became available, presenting the opportunity for significant reductions in drug costs. Objectives To describe the uptake of TNFi biosimilars for psoriasis treatment in the UK and Ireland. Methods This observational cohort study utilizes data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), a national pharmacovigilance study register for patients with psoriasis on systemic treatments. We analysed biosimilar uptake trends over time in nine geographical regions of England along with Wales, Scotland, Northern Ireland and the Republic of Ireland. We assessed the incidence of switching to biosimilars in an originator-user cohort (switchers). Patients on originators infliximab, etanercept and adalimumab at the time originator patents expired, entered the cohort on 1 February 2015, August 2015 and October 2018, respectively, and were followed up until 31 October 2021. Trends in biosimilar initiations were assessed in an adalimumab-naïve cohort who started adalimumab between 1 October 2018 and 31 July 2019 (starters). We assessed the associations between patient factors and originator-to-biosimilar switching and biosimilar initiation using a multivariable Cox regression model and a multivariable logistic regression model, respectively. Results Included in the originator-user cohort were 4202 patients (209 on infliximab, 742 on etanercept and 3251 on adalimumab). For infliximab, etanercept and adalimumab, respectively, the cumulative incidence of originator-to-biosimilar switching increased with time to 14.8%, 23.6% and 66.6% after 3 years. Across geographical regions, 3-year switching rates varied from 0% to 43.7% for infliximab; from 0% to 40.4% for etanercept; and from 12.5% to 84.3% for adalimumab. Out of the 528 patients included in the adalimumab-naïve cohort, 67.8% started on biosimilars. Originator-to-biosimilar switching and biosimilar initiation were more common in men and in patients who had lower Psoriasis Area and Severity Index at cohort entry. Conclusions The uptake of biosimilars increased over time and varied considerably across the UK and Ireland; adalimumab had the highest biosimilar uptake rate compared with that of other TNFi drugs.

ObjectivesTo investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression.ResultsOf 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25–2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39–2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42–0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19.ConclusionOlder age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

During the COVID-19 pandemic, rapid, real-world evidence is essential for the development of knowledge and subsequent public health response. In dermatology, provider-facing and patient-facing registries focused on COVID-19 have been important sources of research and new information aimed at guiding optimal patient care. The 7 dermatology registries included in this update now include more than 8000 case reports sourced from physicians and patients from countries all over the world.

Indirect excess morbidity in the COVID-19 pandemic may arise from public health risk-mitigation efforts such as stay-at-home orders and re-purposing of healthcare services1 . Increased mental health disorders and shortfalls in the care of long-term conditions are described.

A stratified medicine approach for the treatment of psoriasis promises greater certainty of clinical decision making through prediction of response on the basis of clinical, pharmacological, and -omics data from an individual patient. As yet, there is no predictive model for treatment response in routine clinical use for psoriasis. The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) Consortium is a United Kingdom Medical Research Council‒funded, academic‒industrial stratified medicine consortium established with the objective of discovering the predictors and stratifiers of response of psoriasis to biologic therapies. A showcase meeting was convened and attended by 80 stakeholders at the Royal College of Physicians, London, United Kingdom on 18 November 2019. The purpose was to disseminate the research findings from the PSORT consortium discovered thus far. This report summarizes the presentations made on the day and the significant advances made by PSORT toward a stratified medicine approach to the management of psoriasis.

Objectives: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Methods: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)–based heritability estimate (h2SNP) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. Results: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10−9), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10−45) and Wnt signaling (adjusted P = 9.5 × 10−58). The heritability of PsA in this cohort was found to be moderate (h2SNP = 0.63), which was similar to the heritability of PsC (h2SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. Conclusion: Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Background: New technologies have enabled the potential for stratified medicine in psoriasis. It is important to understand patients’ preferences to enable the informed introduction of stratified medicine, which is likely to involve a number of individual tests that could be collated into a prescribing algorithm for biological drug selection to be used in clinical practice. Objectives: To quantify patient preferences for an algorithm-based approach to prescribing biologics (‘biologic calculator’) in psoriasis. Methods: An online survey comprising a discrete choice experiment (DCE) was conducted to elicit the preferences of two purposive samples of adults living with psoriasis in the UK, identified from a psoriasis patient organization (Psoriasis Association) and an online panel provider (Dynata). Respondents chose between two biologic calculators and conventional prescribing described using five attributes: treatment delay; positive predictive value; negative predictive value; risk of infection; and cost saving to the National Health Service. Each participant selected their preferred alternative from six hypothetical choice sets. Additional data, including sociodemographic characteristics, were collected. Choice data were analysed using conditional logit and fully correlated random parameters logit models. Results: Data from 212 respondents (67 from the Psoriasis Association and 145 from Dynata) were analysed. The signs of all estimated coefficients were consistent with a priori expectations. Respondents had a strong preference for a high predictive accuracy and avoiding serious infection, but there was evidence of systematic differences in preferences between the samples. Conclusions: This study indicates that individuals with psoriasis would value a biologic calculator and suggested that such a biologic calculator should have sufficient accuracy to predict future response and risk of serious infection from the biologic.

Background The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed. Objectives We aim to identify subgroups of psoriasis patients treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management. Methods Here we apply latent class mixed modelling, to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 subjects pooled across four clinical trials. Results We discovered four, discrete classes of global response trajectories, each characterised in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. Body Mass Index, baseline PASI, and prevalence of different manifestations. Our results were verified in a second cohort of clinical trials subjects, where similar trajectories following initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories. Conclusion These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterising the subgroups with additional molecular and pharmacological data.

Background: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies. Methods: We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate). Findings: We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49). Interpretation: COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy. Funding: UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.

Contains fulltext : 237768.pdf (Publisher’s version ) (Open Access) The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis.

Objective.To determine the risk of a diagnosis of osteoarthritis (OA) in patients with psoriatic arthritis (PsA) compared to patients with psoriasis and a general population cohort.Methods.Incident PsA patients aged 18–89 years at diagnosis were identified from the United Kingdom Clinical Practice Research Datalink between 1998 and 2014. All patients with PsA were matched to 2 cohorts of patients, both at a 1:4 ratio. The first cohort included patients with psoriasis (and no PsA) and the second was a general population cohort (with no psoriasis or PsA). The baseline prevalence of OA was calculated for each study cohort. The incidence of OA was calculated, and adjusted relative risks (RRadj) were calculated using conditional Poisson regression.Results.We identified 6783 incident PsA patients. The baseline prevalence of OA ranged from 22.1% (95% CI 21.1–23.1) in the PsA cohort to 12.6% (95% CI 12.2–13.0) and 11.0% (95% CI 10.6–11.3) in the psoriasis and general population cohorts, respectively. The incidence of OA was significantly higher in the PsA cohort compared to the psoriasis and general population cohorts after adjusting for BMI (RRadj 1.68, 95% CI 1.46–1.93, and RRadj 1.86, 95% CI 1.62–2.14, respectively).Conclusion.An increased risk of OA was observed in patients with PsA compared to patients with psoriasis alone and those in the general population. Further work is needed to determine whether this reflects a true increase in OA risk or misdiagnosed PsA, and the extent to which it can be explained by differences in the opportunity for OA diagnosis between cohorts.

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2–4.2) and in 10.6% (95% CI = 7.9–13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (−0.62 μg/ml [95% CI = −1.190 to −0.30] and −0.74 μg/ml [95% CI = −1.09 to −0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0–9.9] and 1.9 [95% CI = 0.4–4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9–8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

Objective Headaches affect 88% of reproductive-aged women. Yet data are limited addressing treatment of headache in pregnancy. While many women experience improvement in pregnancy, primary and secondary headaches can develop. Consequently, pregnancy is a time when headache diagnosis can influence maternal and fetal interventions. This study was aimed to summarize existing randomized control trials (RCTs) addressing headache treatment in pregnancy. Study Design We searched PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS from January 1, 1970 through June 31, 2019. Studies were eligible if they were English-language RCTs addressing treatment of headache in pregnancy. Conference abstracts and studies investigating postpartum headache were excluded. Three authors reviewed English-language RCTs addressing treatment of antepartum headache. To be included, all authors agreed each article to meet the following criteria: predefined control group, participants underwent randomization, and treatment of headache occurred in the antepartum period. If inclusion criteria were met no exclusions were made. Our systematic review registration number was CRD42019135874. Results A total of 193 studies were reviewed. Of the three that met inclusion criteria all were small, with follow-up designed to measure pain reduction and showed statistical significance. Conclusion Our systematic review of RCTs evaluating treatment of headache in pregnancy revealed only three studies. This paucity of data limits treatment, puts women at risk for worsening headache disorders, and delays diagnosis placing both the mother and fetus at risk for complications.

Background: COVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. Here, we aimed to assess immune responses following the second dose.Methods: In this longitudinal cohort study, we recruited individuals with psoriasis who were receiving methotrexate or targeted biological monotherapy (ie, tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South-East England. The healthy control cohort were volunteers without psoriasis, not receiving immunosuppression. Immunogenicity was evaluated immediately before, on day 28 after the first BNT162b2 vaccination and on day 14 after the second dose (administered according to an extended interval regimen). Here, we report immune responses following the second dose. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as titres of total spike-specific IgG and of neutralising antibody to wild-type, alpha (B.1.1.7), and delta (B.1.617.2) SARS-CoV-2 variants, and cellular immunity defined as spike-specific T-cell responses (including numbers of cells producing interferon-γ, IL-2, IL-21).Findings: Between Jan 14 and April 4, 2021, 121 individuals were recruited, and data were available for 82 participants after the second vaccination. The study population included patients with psoriasis receiving methotrexate (n=14), TNF inhibitors (n=19), IL-17 inhibitors (n=14), IL-23 inhibitors (n=20), and 15 healthy controls, who had received both vaccine doses. The median age of the study population was 44 years (IQR 33-52), with 43 (52%) males and 71 (87%) participants of White ethnicity. All participants had detectable spike-specific antibodies following the second dose, and all groups (methotrexate, targeted biologics, and healthy controls) demonstrated similar neutralising antibody titres against wild-type, alpha, and delta variants. By contrast, a lower proportion of participants on methotrexate (eight [62%] of 13, 95% CI 32-86) and targeted biologics (37 [74%] of 50, 60-85; p=0·38) had detectable T-cell responses following the second vaccine dose, compared with controls (14 [100%] of 14, 77-100; p=0·022). There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 106 cells 160 [IQR 10-625]), targeted biologics (169 [25-503], p=0·56), and controls (185 [133-328], p=0·41).Interpretation: Functional humoral immunity (ie, neutralising antibody responses) at 14 days following a second dose of BNT162b2 was not impaired by methotrexate or targeted biologics. A proportion of patients on immunosuppression did not have detectable T-cell responses following the second dose. The longevity of vaccine-elicited antibody responses is unknown in this population.Funding: NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London; The Psoriasis Association.

The COVID-19 pandemic led to a sudden uptake of telemedicine in rheumatology. We analyzed the recent published literature on telemedicine for the diagnosis and management of inflammatory, non-inflammatory and/or autoimmune rheumatic diseases.We performed a registered systematic search (CRD42020202063) for interventional or observational studies published between August 2015 and January 2022. We included studies of telemedicine that reported outcomes (e.g., satisfaction, disease activity, quality of life) in ten or more people with rheumatic disease. Reviewers screened manuscripts, extracted data, and assessed bias.Of the 2,988 potentially eligible studies, 36 reports were included: 27 observational studies, 7 randomized clinical trials, and 2 controlled clinical trials. Studies focused on general rheumatology (n = 18), rheumatoid arthritis (n = 9), gout (n = 3), osteoarthritis (n = 2), unspecified inflammatory arthritis (n = 1), osteoporosis (n = 2), and systemic lupus erythematosus (n = 1). Patient satisfaction with telemedicine was the most common reported outcome (n = 23) with majority of studies demonstrating high levels of satisfaction. Among interventional studies, the effect of telemedicine on the primary outcomes varied, with most finding that telemedicine was as good as usual / in-person care for disease activity control, patient satisfaction, total societal costs, and other patient reported outcomes. Effectiveness and feasibility were high across studies, though most demonstrated a high risk of bias. Meta-analysis was not feasible given the heterogeneity of interventions and outcome instruments utilized.Although the number of studies to date is low, telemedicine may be an effective mode to deliver care for people with rheumatic diseases. Most studies demonstrated limitations due to study design and risk of bias. Randomized clinical studies are needed to determine best uses of telemedicine for the diagnosis and management of rheumatic conditions.

Palmoplantar pustulosis (PPP) is a severe inflammatory skin disorder characterized by eruptions of painful, neutrophil-filled pustules on the palms and soles. Although PPP has a profound effect on quality of life, it remains poorly understood and notoriously difficult to treat.We sought to investigate the immune pathways that underlie the pathogenesis of PPP.We applied bulk and single-cell RNA sequencing (RNA-Seq) methods to the analysis of skin biopsy samples and peripheral blood mononuclear cells. We validated our results by flow cytometry and immune fluorescence microscopy RESULTS: Bulk RNA-Seq of patient skin detected an unexpected signature of T-cell activation, with a significant overexpression of several TPPP is associated with complex T-cell activation patterns and may explain why biologic drugs that target individual T helper cell populations have shown limited therapeutic efficacy.

Introduction Previous drug survival studies of dupilumab in atopic dermatitis (AD) show that many patients continue treatment through 1 year, suggesting that patients experience clinically relevant benefits with long-term treatment. Methods This post hoc analysis included data through week 100 from 391 adult patients from the dupilumab open-label extension (OLE) study who had not achieved the endpoints of at least 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) or an Investigator’s Global Assessment (IGA) score of 0 or 1 with short-term (16 weeks, 300 mg qw or q2w) dupilumab treatment in the parent SOLO 1 or 2 studies. All patients received dupilumab 300 mg qw in the OLE study, irrespective of whether they received qw or 2qw dosing in the parent study. Results Among those who had not achieved EASI-75 or IGA 0/1 during the 16-week parent study, the proportion of patients achieving EASI-75 by week 100 was 91%. The proportion achieving IGA 0 or 1 at week 100 was 45% for patients initially on q2w week dosing and 49% for those on initial qw dosing. Conclusion Long-term dupilumab treatment may be associated with improvement in AD in patients with suboptimal responses during the initial 16 weeks of treatment. Clinical Trial Registration LIBERTY AD SOLO 1: ClinicalTrials.gov identifier NCT02277743; EudraCT 2014-001198-15. LIBERTY AD SOLO 2: ClinicalTrials.gov identifier NCT02277769; EudraCT 2014-002619-40. LIBERTY AD OLE: ClinicalTrials.gov Identifier NCT01949311; EudraCT 2013-001449-15. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00643-4.

BackgroundIt is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes.MethodsWith the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysingroutinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population; and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate).FindingsWe identified 17,672,065 adults; of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in individuals with IMIDs overall compared to individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56); however, this finding may relate to confounding.InterpretationCOVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics.RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed on May 19th, 2021, using the terms “COVID-19”, “SARS-CoV-2” and “rheumatoid arthritis”, “psoriatic arthritis” “ankylosing spondylitis”, “Crohn’s disease” “ulcerative colitis” “hidradenitis suppurativa” and “psoriasis”, to identify primary research articles examining severe COVID-19 outcome risk in individuals with immune-mediated inflammatory diseases (IMIDs) and those on immune modifying therapy. The studies identified (including matched cohort studies and studies in disease-specific registries) were limited by small sample sizes and number of outcomes. Most studies did not show a signal of increased adverse COVID-19 outcomes in those on targeted therapies, with the exception of rituximab. Additionally, disease-specific registries are subject to selection bias and lack denominator populations.Added value of the studyIn our large population-based study of 17 million individuals, including 1 million people with IMIDs and just under 200,000 receiving immune modifying medications, we saw evidence that people with IMIDs had an increased risk of COVID-19-related death compared to the general population after adjusting for potential confounders (age, sex, deprivation, smoking status) (HR 1.23, 95%CI 1.20, 1.27). We saw differences by IMID type, with COVID-19-related death being increased by the most in people with inflammatory joint disease (HR 1.47, 95%CI 1.40, 1.54). We also saw some evidence that those with IMIDs were more likely, compared to the general population, to have COVID-19-related critical care admission/death (HR 1.24, 95%CI 1.21, 1.28) and hospitalisation (HR 1.32, 95%CI 1.29, 1.35).Compared to people with IMIDs taking standard systemics, we saw no evidence of differences in severe COVID-19-related outcomes with TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-6 inhibitors and JAK inhibitors. However, there was some evidence that rituximab was associated with an increased risk of COVID-19-related death (HR 1.68, 95%CI 1.11, 2.56) and death/critical care admission (HR 1.92, 95%CI 1.31, 2.81). We also saw evidence of an increase in COVID-19-related hospital admissions in people prescribed rituximab (HR 1.59, 95%CI 1.16, 2.18) or JAK inhibition (HR 1.81, 95%CI 1.09, 3.01) compared to those on standard systemics, although this could be related to worse underlying health rather than the drugs themselves, and numbers of events were small.This is the first study to our knowledge to use high-cost drug data on medicines supplied by hospitals at a national scale in England (to identify targeted therapies). The availability of these data fills an important gap in the medication record of those with more specialist conditions treated by hospitals creating an important opportunity to generate insights to these conditions and these medicationsImplications of all of the available evidenceOur study offers insights into future risk mitigation strategies and SARS-CoV-2 vaccination priorities for individuals with IMIDs, as it highlights that those with IMIDs and those taking rituximab may be at risk of severe COVID-19 outcomes. Critically, our study does not show a link between most targeted immune modifying medications compared to standard systemics and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes that we saw in people with IMIDs and those treated with rituximab merits further study.

BackgroundThe increase in the number of available biologic agents for psoriasis has led to an urgent need to evaluate their associated risk of serious infections to help inform clinical decisions.MethodologyWe systematically searched PubMed, Medline, Embase, and Cochrane databases for biologics targeting TNF (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/23 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, risankizumab, and tildrakizumab) for the primary outcome serious infections, at 10– 16 weeks, 1 year and 3 years. Peto’s method (fixed effect model) was used to estimate the pooled odds ratio (OR) in meta-analyses comparing biologics with one another, methotrexate, or placebo.ResultsForty-three publications (49 trials) consisting of 29,724 participants met our inclusion criteria. Serious infections across all studies were low (n=97) at 10–16 weeks and did not show an increased risk with biologic therapies compared with placebo. Seven head-to-head RCTs were identified, most of which showed no significant difference in the risk of serious infections at 10–16 weeks and at 1 year. Adalimumab was not associated with a significant increased risk of serious infections compared with methotrexate in children at 10–16 weeks.ConclusionsBiologics for psoriasis were not associated with an increased risk of serious infections compared with placebo or one another at 10–16 weeks. Longer-term, real-world data with larger sample sizes are warranted.

Objective Approximately one-third of maternal deaths occur postpartum. Little is known about the intersection between the postpartum period, emergency department (ED) use, and opportunities to reduce maternal mortality. The primary objectives of this systematic review are to explore the incidence of postpartum ED use, identify postpartum disease states that are evaluated in the ED, and summarize postpartum ED use by race/ethnicity and payor source. Study Design We searched PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, Cochrane CENTRAL, Social Services Abstracts, and Scopus from inception to September 19, 2019. Each identified abstract was screened by two authors; the full-text manuscripts of all studies deemed to be potential candidates were then reviewed by the same two authors and included if they were full-text, peer-reviewed articles in the English language with primary patient data reporting care of a female in the ED in the postpartum period, defined as up to 1 year after the end of pregnancy. Results A total of 620 were screened, 354 records were excluded and 266 full-text articles were reviewed. Of the 266 full-text articles, 178 were included in the systematic review; of these, 108 were case reports. Incidence of ED use by postpartum females varied from 4.8 to 12.2% in the general population. Infection was the most common reason for postpartum ED evaluation. Young females of minority race and those with public insurance were more likely than whites and those with private insurance to use the ED. Conclusion As many as 12% of postpartum women seek care in the ED. Young minority women of lower socioeconomic status are more likely to use the ED. Since approximately one-third of maternal deaths occur in the postpartum period, successful efforts to reduce maternal mortality must include ED stakeholders. This study is registered with the Systematic Review Registration (identifier: CRD42020151126). Key Points

Summary Background Patients on therapeutic immunosuppressants for immune-mediated inflammatory diseases were excluded from COVID-19 vaccine trials. We therefore aimed to evaluate humoral and cellular immune responses to COVID-19 vaccine BNT162b2 (Pfizer-BioNTech) in patients taking methotrexate and commonly used targeted biological therapies, compared with healthy controls. Given the roll-out of extended interval vaccination programmes to maximise population coverage, we present findings after the first dose. Methods In this cohort study, we recruited consecutive patients with a dermatologist-confirmed diagnosis of psoriasis who were receiving methotrexate or targeted biological monotherapy (tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South East England. Consecutive volunteers without psoriasis and not receiving systemic immunosuppression who presented for vaccination at Guy's and St Thomas' NHS Foundation Trust (London, UK) were included as the healthy control cohort. All participants had to be eligible to receive the BNT162b2 vaccine. Immunogenicity was evaluated immediately before and on day 28 (±2 days) after vaccination. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as neutralising antibody responses to wild-type SARS-CoV-2, and spike-specific T-cell responses (including interferon-γ, IL-2, and IL-21) 28 days after vaccination. Findings Between Jan 14 and April 4, 2021, 84 patients with psoriasis (17 on methotrexate, 27 on TNF inhibitors, 15 on IL-17 inhibitors, and 25 on IL-23 inhibitors) and 17 healthy controls were included. The study population had a median age of 43 years (IQR 31–52), with 56 (55%) males, 45 (45%) females, and 85 (84%) participants of White ethnicity. Seroconversion rates were lower in patients receiving immunosuppressants (60 [78%; 95% CI 67–87] of 77) than in controls (17 [100%; 80–100] of 17), with the lowest rate in those receiving methotrexate (seven [47%; 21–73] of 15). Neutralising activity against wild-type SARS-CoV-2 was significantly lower in patients receiving methotrexate (median 50% inhibitory dilution 129 [IQR 40–236]) than in controls (317 [213–487], p=0·0032), but was preserved in those receiving targeted biologics (269 [141–418]). Neutralising titres against the B.1.1.7 variant were similarly low in all participants. Cellular immune responses were induced in all groups, and were not attenuated in patients receiving methotrexate or targeted biologics compared with controls. Interpretation Functional humoral immunity to a single dose of BNT162b2 is impaired by methotrexate but not by targeted biologics, whereas cellular responses are preserved. Seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression. Real-world pharmacovigilance studies will determine how these findings reflect clinical effectiveness. Funding UK National Institute for Health Research.

Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.

In recent years, a growing interest in the characterization of the molecular basis of psoriasis has been observed. However, despite the availability of a large amount of molecular data, many pathogenic mechanisms of psoriasis are still poorly understood. In this study, we performed an integrated analysis of 23 public transcriptomic datasets encompassing both lesional and uninvolved skin samples from psoriasis patients. We defined comprehensive gene co-expression network models of psoriatic lesions and uninvolved skin. Moreover, we collected, curated and exploited a wide range of functional information from multiple public sources in order to systematically annotate the inferred networks.The integrated transcriptomics analysis of public datasets shed light on a number of genes which are frequently deregulated in the psoriatic lesion compared with the unaffected skin in a large number of studies. In particular, CRABP2, LCN2, S100A12 and PDZK1IP1 were found to be deregulated in all of the datasets analyzed.Furthermore, the analysis of co-expression networks highlights genes showing aberrant patterns of connectivity in the lesional network as compared to the network inferred from unaffected skin samples. For instance, we identified co-expression patterns of SERPINB4, KYNU and S100A12 as being the most affected by the disease. Network analysis allowed us to identify YPEL1 and HUS1 as plausible, previously unknown, actors in the expression of the psoriasis phenotype. In addition, by exploiting topological properties of the network models, we highlighted a set of 250 non-deregulated genes, 223 of which have never been associated with the disease before, including CACNA1A, HADH, ATP5MC1 and CBARP among others.Finally, we characterized specific communities of co-expressed genes sustaining relevant molecular functions and specific immune cell types expression signatures playing a role in the psoriasis lesion. Overall, integrating experimental driven results with curated functional information from public repositories represents an efficient approach to empower knowledge generation about psoriasis and may be applicable to other complex diseases.

BackgroundIndirect excess morbidity has emerged as a major concern in the COVID-19 pandemic. People with psoriasis may be particularly vulnerable to this because of prevalent anxiety and depression, multimorbidity and therapeutic use of immunosuppression.ObjectiveCharacterise the factors associated with worsening psoriasis in the COVID-19 pandemic, using mental health status (anxiety and depression) as the main exposure of interest.MethodsGlobal cross-sectional study using a primary outcome of self-reported worsening of psoriasis. Individuals with psoriasis completed an online self-report questionnaire (PsoProtectMe; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection Me) between May 2020 and January 2021. Each individual completed a validated screen for anxiety (Generalized Anxiety Disorder-2) and depression (Patient Health Questionnaire-2). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression.Results4,043 people with psoriasis (without COVID-19) from 86 countries self-reported to PsoProtectMe (mean age 47.2 years [SD 15.1]; mean BMI 27.6kg/m2 [SD 6.0], 2,684 [66.4%] female and 3,016 [74.6%] of white European ethnicity). 1,728 (42.7%) participants (1322 [77%] female) reported worsening of their psoriasis in the pandemic. A positive screen for anxiety or depression associated with worsening psoriasis in age and gender adjusted (OR 2.04, 95% CI 1.77-2.36), and fully adjusted (OR 2.01, 95% CI 1.72-2.34) logistic regression models. Female sex, obesity, shielding behaviour and systemic immunosuppressant non-adherence also associated with worsening psoriasis. The commonest reason for non-adherence was concern regarding complications related to COVID-19.ConclusionsThese data indicate an association between poor mental health and worsening psoriasis in the pandemic. Access to holistic care including psychological support may mitigate potentially long-lasting effects of the pandemic on health outcomes in psoriasis. The study also highlights an urgent need to address patient concerns about immunosuppressant-related risks, which may be contributing to non-adherence.

High-quality dermatology patient registries often require considerable time to develop and produce meaningful data. Development time is influenced by registry complexity and regulatory hurdles that vary significantly nationally and institutionally. The rapid emergence of the coronavirus disease 2019 (COVID-19) global pandemic has challenged health services in an unprecedented manner. Mobilization of the dermatology community in response has included rapid development and deployment of multiple, partially harmonized, international patient registries, reinventing established patient registry timelines. Partnership with patient organizations has demonstrated the critical nature of inclusive patient involvement. This global effort has demonstrated the value, capacity, and necessity for the dermatology community to adopt a more cohesive approach to patient registry development and data sharing that can lead to myriad benefits. These include improved utilization of limited resources, increased data interoperability, improved ability to rapidly collect meaningful data, and shortened response times to generate real-world evidence. We call on the global dermatology community to support the development of an international federation of patient registries to consolidate and operationalize the lessons learned during this pandemic. This will provide an enduring means of applying this knowledge to the maintenance and development of sustainable, coherent, and impactful patient registries of benefit now and in the future.