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Two years after its inception, Young Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (Y-GRAPPA) has established itself as a productive network for junior investigators and clinicians. The group's achievements in the last year include updating the educational GRAPPA slide library, the "Bring a Derm" campaign to expand the GRAPPA community to include more dermatologists, and the publication of multiple "Do Not Miss" newsletters covering the highlights on PsDs from the major international conferences (American Academy of Dermatology [AAD] Annual Meeting, European Alliance of Associations for Rheumatology [EULAR] Congress, European Academy of Dermatology and Venereology [EADV] Congress, and American College of Rheumatology [ACR] Convergence).
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BACKGROUND: The COVID-19 pandemic has highlighted health disparities affecting ethnic minority communities. There is growing concern about the lack of diversity in clinical trials. This study aimed to assess the representation of ethnic groups in UK-based COVID-19 randomised controlled trials (RCTs). METHODS: A systematic review and meta-analysis were undertaken. A search strategy was developed for MEDLINE (Ovid) and Google Scholar (1st January 2020-4th May 2022). Prospective COVID-19 RCTs for vaccines or therapeutics that reported UK data separately with a minimum of 50 participants were eligible. Search results were independently screened, and data extracted into proforma. Percentage of ethnic groups at all trial stages was mapped against Office of National Statistics (ONS) statistics. Post hoc DerSimonian-Laird random-effects meta-analysis of percentages and a meta-regression assessing recruitment over time were conducted. Due to the nature of the review question, risk of bias was not assessed. Data analysis was conducted in Stata v17.0. A protocol was registered (PROSPERO CRD42021244185). RESULTS: In total, 5319 articles were identified; 30 studies were included, with 118,912 participants. Enrolment to trials was the only stage consistently reported (17 trials). Meta-analysis showed significant heterogeneity across studies, in relation to census-expected proportions at study enrolment. All ethnic groups, apart from Other (1.7% [95% CI 1.1-2.8%] vs ONS 1%) were represented to a lesser extent than ONS statistics, most marked in Black (1% [0.6-1.5%] vs 3.3%) and Asian (5.8% [4.4-7.6%] vs 7.5%) groups, but also apparent in White (84.8% [81.6-87.5%] vs 86%) and Mixed 1.6% [1.2-2.1%] vs 2.2%) groups. Meta-regression showed recruitment of Black participants increased over time (p = 0.009). CONCLUSIONS: Asian, Black and Mixed ethnic groups are under-represented or incorrectly classified in UK COVID-19 RCTs. Reporting by ethnicity lacks consistency and transparency. Under-representation in clinical trials occurs at multiple levels and requires complex solutions, which should be considered throughout trial conduct. These findings may not apply outside of the UK setting.
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COVID-19 , Humanos , COVID-19/terapia , Minorías Étnicas y Raciales , Etnicidad , Sesgo , Reino Unido/epidemiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.
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Artritis Psoriásica , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Uveítis , Humanos , AdalimumabRESUMEN
The human body consists of millions of commensal bacteria (the microbiome), with the intestinal tract being the most prevalent site of colonization. This colonization process begins at birth, and despite numerous factors such as ageing, diet and drug use affecting the microbiome make-up, by adulthood the composition of the gut bacteria is relatively consistent across local populations. The recent advent of new scientific techniques has enabled us to explore how the microbiome affects health and, in particular, has shed light on the involvement of the microbiome in the pathogenesis of inflammatory disease. In this review we highlight the current evidence for microbiome manipulation in inflammatory arthritis in animal and human models and discuss potential therapeutics targeting the microbiome as treatment for these diseases.
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Artritis/microbiología , Microbioma Gastrointestinal , Animales , Antibacterianos/uso terapéutico , Artritis/tratamiento farmacológico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/microbiología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/microbiología , Bacterias/aislamiento & purificación , Disbiosis/complicaciones , Disbiosis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Probióticos/uso terapéutico , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/microbiología , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/microbiologíaAsunto(s)
Atención a la Salud/métodos , Enfermedades Reumáticas/terapia , Reumatología/métodos , Telemedicina , Atención Ambulatoria , Inteligencia Artificial , Betacoronavirus , COVID-19 , Centers for Medicare and Medicaid Services, U.S. , Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades , Terapia de Infusión a Domicilio , Humanos , Invenciones , Pandemias , Examen Físico , Neumonía Viral/epidemiología , Enfermedades Reumáticas/diagnóstico , SARS-CoV-2 , Autoexamen , Medicina Estatal , Tecnología , Teléfono , Reino Unido/epidemiología , Estados Unidos/epidemiología , Comunicación por VideoconferenciaRESUMEN
Adoptive immunotherapy using genetically targeted T-cells has recently begun to achieve impressive clinical impact in selected tumor types. Furthermore, long-term follow-up studies indicate thus far that integrating viral vectors do not elicit clinically evident genotoxicity in T-cells, unlike hematopoietic stem cells. The optimism engendered by this clinical experience provides a platform for consideration of the extended use of this technology in other disease types. One area of particular interest entails the harnessing of regulatory T-cells (Tregs) in order to down-regulate unwanted immune responses. Increasing evidence supports the efficacy of this approach in pre-clinical models of autoimmune disease and allograft rejection. Nonetheless, questions remain about optimal host cell, transgene cargo, phenotypic stability of engineered cells in vivo and potential for toxicity. Here, we review the evidence that genetically engineered Tregs can effectively dampen pathogenic immune responses and critically evaluate the prospects for clinical development of this approach.
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Inmunoterapia Adoptiva , Linfocitos T Reguladores/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Humanos , Medición de RiesgoRESUMEN
Young-GRAPPA (Y-GRAPPA) was introduced at the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting. Here we present the 1-year progress of Y-GRAPPA and future plans of this enthusiastic group of young clinicians and early career researchers interested in psoriasis and psoriatic arthritis.
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Artritis Psoriásica , Dermatología , Psoriasis , Reumatología , HumanosRESUMEN
BACKGROUND: Over recent years the lack of patient involvement in the design, set-up and implementation of clinical research studies has been well recognised; as such there has been a drive within research communities to increase patient participation. Patient perspectives on telemedicine differ widely, with variation in whether patients feel remote consultations are beneficial. By means of a patient-driven survey, we aimed to formally evaluate patient perspectives on its benefits and pitfalls, focusing on patients with psoriatic arthritis (PsA). METHODS: An e-survey was developed by two patient representatives on the BritPACT steering committee, with a view to determining unmet needs and the perceived impact on clinical care of virtual consultations amongst patients with PsA. RESULTS: 128 patients responded to the e-survey. 109 patients rated the effectiveness of their telemedicine appointment and, of these, 18% felt their virtual consultation was very/extremely effective compared to an in-clinic consultation and 49% felt it was somewhat/equally as effective; furthermore, 48% (51/107) felt that such virtual consultations would be of benefit to them after the pandemic. 36% of respondents felt their virtual consultation was not as effective as an in-clinic review. Themes identified from open-ended questions included the lack of visual cues, lack of physical examination and effect on rapport and ease of open communication as the main pitfalls of virtual consultations. Patients with well-controlled symptoms appeared more satisfied with remote reviews compared to those with active disease, though on the whole respondents recognised the benefits, such as saving travel time and costs. Those who had an established relationship with their health professional appeared less concerned regarding virtual consultations though a recurring view was that newly diagnosed patients should have in-clinic appointments to build rapport and improve symptom control at an early stage. CONCLUSIONS: Overall patients' perspectives on virtual consultations varied widely though patients with well-controlled symptoms and those who had a previously established relationship with their healthcare professionals and well-controlled disease appeared more satisfied with remote reviews.
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At the 2021 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, a separate group was created (Young-GRAPPA) to address the challenges of young researchers and physicians beginning their careers. This paper presents the initial organizational framework and different components and aims of this group. We were able to enroll over 50 young researchers as a result of this meeting.
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Artritis Psoriásica , Dermatología , Psoriasis , Reumatología , Artritis Psoriásica/diagnóstico , Humanos , OrganizacionesRESUMEN
AIMS: The ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). METHODS: A search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included. RESULTS: A total of 765 articles were retrieved and after review, 44 articles (22 relating to PsV and 22 to PsA) met the systematic review's eligibility criteria. One study examined the response to methotrexate, one the response to tofacitinib and all the other studies to biologic disease-modifying antirheumatic drugs (DMARDs). Whilst several studies examined the HLA-C*06 allele in PsV, the results were conflicting. Interleukin (IL)-12 serum levels and polymorphisms in the IL-12B gene show promise as biomarkers of treatment response in PsV. Most, but not all, studies found that higher baseline levels of C-reactive protein (CRP) were associated with a better clinical response to treatment in patients with PsA. CONCLUSION: Several studies have identified biomarkers associated with subsequent response to treatment in psoriatic disease. However, due to the different types of biomarkers, treatments and outcome measures used, firm conclusions cannot be drawn. Further validation is needed before any of these biomarkers translate to clinical practice.
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Objective: Despite recent advances, early diagnosis of psoriatic arthritis (PsA) remains a challenge in clinical practice. Ultrasound (US) could be a useful tool for the diagnosis and management of PsA. The objective of this review was to determine the role of US in early diagnosis of PsA. Methods: We have performed a literature review aiming to evaluate studies on US findings in psoriasis and their predictive value of progression to PsA, as well as studies on US features specific for PsA in comparison with other conditions. Results: A total of 40 studies were included. Sixteen studies assessed US findings in psoriasis, of which only 3 prospectively evaluated the role of US in predicting progression to PsA. Patients with PsA had a greater frequency of US abnormalities, in particular enthesitis and Power Doppler(PD) signal compared to patients with psoriasis only. In the longitudinal studies, psoriatic patients with higher enthesopathy scores at baseline were more likely to progress to PsA. Twenty-four studies evaluated US abnormalities in PsA and compared them to other conditions. Most specific US features that distinguish PsA from psoriasis were PD signal and erosions in joints and entheses. Extra-synovial changes, including peri-tendinous dermal soft tissue oedema with associated PD signal and flexor tendon enthesopathy, as well as thickening of the pulleys in the flexor tendons were highly characteristic for PsA, as they were frequently found in PsA patients, but in none of the RA patients. US-detected entheseal abnormalities in particular erosions and PD signal were more frequent in patients with PsA compared to fibromyalgia. Conclusion: Despite the wide use of US in PsA, more research is needed to identify predictive factors of progression to PsA in patients with psoriasis, as well as to determine most specific US features that differentiate PsA from other conditions.
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OBJECTIVE: We performed a systematic review and metaanalysis to assess rheumatoid arthritis (RA) disease activity during pregnancy using objective disease activity scoring systems. METHODS: A systematic review of PubMed, EMBASE/Medline, Cochrane, and LactMed databases was performed. Our inclusion criteria for analysis were prospective studies, more than 5 patients per study, and data on RA using an objective scoring system conducted by a clinician/health professional. RESULTS: Ten studies were eligible for final analysis, which included 237 patients, of which prepartum data were available for 204 patients. Postpartum disease activity was recorded in 135 pregnancies. CONCLUSION: Disease activity improved in 60% of patients with RA in pregnancy and flared in 46.7% postpartum.
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Artritis Reumatoide/fisiopatología , Embarazo , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Proteína C-Reactiva/análisis , Femenino , Humanos , Periodo Posparto , Estudios Prospectivos , Recurrencia , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Psoriatic disease is a relatively new term which encompasses psoriatic arthritis, psoriasis, and associated comorbidities. In this heterogeneous condition, the study of biomarkers is necessary to direct best therapy. Resulting in significant disability and socioeconomic burden, recent recommendations stress the need for tight control in psoriatic disease. Areas covered: The authors outline recent advances in the understanding of psoriatic disease pathogenesis which has highlighted multiple biomarkers that have been pursued as drug targets with varying degrees of success. Current drugs targeting biomarkers and therapies in development are evaluated. The methods of biomarker discovery through genomics, transcriptomics, proteomics, metabolomics, and study of the microbiome are also discussed. Expert opinion: Targeting biomarkers for therapeutic benefit appears to a promising field with multiple success stories, notably those associated with signaling through T-helper-17 cells. The use of genomics, transcriptomics, proteomics, and more recently metabolomics will help individualize targeted biomarker therapies, assist in monitoring therapeutic success, and ultimately yield novel therapeutic targets. Advances in the development of novel biologic molecules targeting more than one cytokine may offer additional gains in therapeutic response.
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Artritis Psoriásica/tratamiento farmacológico , Descubrimiento de Drogas/métodos , Psoriasis/tratamiento farmacológico , Animales , Artritis Psoriásica/patología , Biomarcadores/metabolismo , Genómica/métodos , Humanos , Metabolómica/métodos , Proteómica/métodos , Psoriasis/patología , TranscriptomaRESUMEN
Psoriatic arthritis (PsA) causes inflammation in and around the joints and usually affects people who already have psoriasis. However, some patients develop the joint problems before the psoriasis. Currently, there are five anti-TNF-α agents licensed for use in patients with PsA: adalimumab, certolizumab pegol, etanercept, golimumab and infliximab. Golimumab, a human monoclonal antibody, has been approved by the US FDA for the treatment of PsA and is targeted against the pro-inflammatory molecule TNF-α. The Phase III GO-REVEAL study confirmed this drug was well tolerated and showed significant improvement in disease activity compared with placebo.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/inmunología , Humanos , Inducción de Remisión , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/inmunologíaAsunto(s)
Vacunas contra la COVID-19 , COVID-19 , Etnicidad , Humanos , Inmunogenicidad Vacunal , Grupos Raciales , SARS-CoV-2RESUMEN
We report a 59-year-old lifelong smoker with severe chronic obstructive pulmonary disease who presented with an acute onset 3-day history of left iliac fossa pain and abdominal distension. Clinical examination revealed a palpable mass in the left iliac fossa. The differential diagnosis was that of a diverticular abscess or colonic tumour. She subsequently underwent a CT scan which showed extensive metastatic liver disease from a primary lung tumour, with hepatomegaly abutting the anterior abdominal wall in the left iliac fossa.