83 results found
Jethwa H, Wong R, Abraham S, 2021, Covid-19 vaccine trials: Ethnic diversity and immunogenicity, VACCINE, Vol: 39, Pages: 3541-3543, ISSN: 0264-410X
Miguens Blanco J, Liu Z, Mullish BH, et al., 2021, A Phenomic Characterization of the Gut Microbiota - Associations with Psoriatic Arthritis and Ankylosing Spondylitis, World Microbe Forum
Helo Y, Searle GE, Borgheese F, et al., 2020, Specificity of translocator protein-targeted positron emission tomography in inflammatory joint disease, EJNMMI Research, Vol: 10, ISSN: 2191-219X
ObjectiveExpression of the translocator protein (TSPO) on inflammatory cells has facilitated imaging of synovitis with TSPO-targeted positron emission tomography (PET). We aimed to quantitatively assess the specificity of the second-generation TSPO PET radioligand, [11C]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study.MethodsThree IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [11C]PBR28-PET scans before and after administration of 90 mg of oral emapunil (XBD-173), a TSPO ligand the same day. Radial arterial blood sampling was performed throughout the scan, and total radioactivity and radioactive metabolites were obtained. A semi-automated method was used to generate regions of interest. Standardized uptake value (SUV) and SUV ratio corrected for activity in bone and blood between 50 and 70 min (SUVr50–70 bone, SUVr50–70 blood, respectively) and PET volume of distribution (VT) of the radioligand were calculated.ResultsA mean [11C]PBR28 radioactivity of 378 (range 362–389) MBq was administered. A significant decrease (p < 0.05) in VT, SUVr50–70 bone and SUVr50–70 blood observed after oral emapunil confirmed the TSPO specificity of [11C]PBR28. A decrease in SUV was not observed in the post-block scan.Conclusion[11C]PBR28 is TSPO-specific radioligand in IJD patients. Simplified PET protocols with static PET acquisition can be used in the management and evaluation of novel therapeutics that target TSPO overexpressing cells.
Jethwa H, Sullivan A, Abraham S, 2020, COVID-19 and Immunomodulatory Therapy - Can We Use Data from Previous Viral Pandemics?, JOURNAL OF RHEUMATOLOGY, Vol: 47, Pages: 1734-1737, ISSN: 0315-162X
Miguens Blanco J, Borghese F, McHugh N, et al., 2020, Longitudinal profiling of the gut microbiome in patients with psoriatic arthritis and ankylosing spondylitis: a multicentre, prospective, observational study, BMC Rheumatology, Vol: 4, Pages: 1-10, ISSN: 2520-1026
Background : Psoriasis is a chronic inflammatory disease of the skin affecting 2-3% ofUK population. 30% of people affected by psoriasis will develop a distinct form ofarthritis within 10 years of the skin condition onset. Although the pathogenesis ofpsoriatic arthritis is still unknown, there is a genetic predisposition triggered byenvironmental factors. Limited but convincing evidence link the gut microbiome topsoriatic arthritis. The Microbiome in Psoriatic ARThritis (Mi-PART) study propose is tocharacterise the microbiome-metabolic interface in patients affected by psoriaticarthritis to deepen our understanding of the pathogenesis of the disease.Methods : This is a multicentre, prospective, observational study. Psoriatic arthritis (n= 65) and ankylosing spondylitis (n = 30) patients will be recruited in addition to acontrol group of healthy volunteers (n = 30). Patients eligibility will be evaluated againstthe Criteria for Psoriatic Arthritis (CASPAR), the Bath Ankylosing Spondylitis ActivityIndex (BASDAI) and the healthy volunteers who fulfil study inclusion and exclusioncriteria.Information regarding their medical and medication history, demographics, diet andlifestyle will be collected. All the participants in the study will be asked to complete a 7-day food diary, to provide stool samples and to complete quality of life questionnaires.Routine clinical laboratory tests will be performed on blood and urine samples. Patientsand healthy volunteers with gastrointestinal symptoms, previous history of cancer,gastrointestinal surgery in the previous 6 months or alcohol abuse will be excludedfrom the study.Discussion : The aim of this trial is to characterise the microbiome of psoriatic arthritispatients and to compare it with microbiome of healthy volunteers and of patient withankylosing spondylitis in order to define if different rheumatologic conditions areassociated with characteristic microbiome profiles. Investigating the role of themicrobiome in the develop
Gkrouzman E, Wu DD, Jethwa H, et al., 2020, Telemedicine in Rheumatology at the Advent of the COVID-19 Pandemic., HSS J, Pages: 1-4, ISSN: 1556-3316
Coates LC, Abraham S, Tillett W, et al., 2020, Performance and Predictors of Minimal Disease Activity Response in Peripheral Spondyloarthritis Patients Treated With Adalimumab., Arthritis Care Res (Hoboken)
OBJECTIVES: To examine concurrent validity and discrimination of modified minimal disease activity (mMDA) criteria in peripheral spondyloarthritis (pSpA) following OMERACT filter principles and determine predictors of mMDA response. METHODS: Four mMDA versions were derived in the ABILITY-2 study using the SPondyloArthritis Research Consortium of Canada (SPARCC) or Leeds Enthesitis Index (LEI) but excluding psoriasis. To assess concurrent validity, mMDA versions were correlated with Peripheral SpondyloArthritis Response Criteria (PSpARC) remission, Ankylosing Spondylitis Disease Activity Score for inactive disease (ASDAS ID), and physician global. Treatment discrimination was assessed between adalimumab and placebo at week 12. Multiple logistic regression was used to determine baseline predictors of long-term mMDA responses and sustained mMDA. RESULTS: The four mMDA versions showed a stronger positive correlation with PSpARC remission (rtet >0.95) versus ASDAS ID (rtet >0.75) at week 12 and years 1-3 and were able to show discrimination (p<0.001). Responsiveness was shown at week 12; significantly more patients receiving adalimumab versus placebo achieved all four versions of mMDA. Approximately 40-60% of adalimumab-treated patients achieved mMDA-LEI or SPARCC at years 1-3. Achieving mMDA response after 12 weeks of adalimumab treatment was a robust positive predictor of attaining long-term mMDA through 3 years (odds ratios: 11.38-27.13 for mMDA-LEI; 17.98-37.85 for mMDA-SPARCC). CONCLUSIONS: All four versions of mMDA showed concurrent validity and discriminated well between adalimumab and placebo treatment groups. Early mMDA response is a more consistent predictor of long-term mMDA achievement than baseline characteristics. The 5 of 6 versions of mMDA could be an appropriate treatment target in pSpA patients.
Jethwa H, Abraham S, 2020, Should we be using the Covid-19 outbreak to prompt us to transform our rheumatology service delivery in the technology age?, Rheumatology, Vol: 59, Pages: 1469-1471, ISSN: 1462-0324
Abraham S, Juel HB, Bang P, et al., 2019, Safety and immunogenicity of the chlamydia vaccine candidate CTH522 adjuvanted with CAF01 liposomes or aluminium hydroxide: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial, Lancet Infectious Diseases, Vol: 19, Pages: 1091-1100, ISSN: 1473-3099
BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection worldwide. National screening programmes and antibiotic treatment have failed to decrease incidence, and to date no vaccines against genital chlamydia have been tested in clinical trials. We aimed to assess the safety and immunogenicity, in humans, of a novel chlamydia vaccine based on a recombinant protein subunit (CTH522) in a prime-boost immunisation schedule. METHODS: This phase 1, first-in-human, double-blind, parallel, randomised, placebo-controlled trial was done at Hammersmith Hospital in London, UK, in healthy women aged 19-45 years. Participants were randomly assigned (3:3:1) to three groups: CTH522 adjuvanted with CAF01 liposomes (CTH522:CAF01), CTH522 adjuvanted with aluminium hydroxide (CTH522:AH), or placebo (saline). Participants received three intramuscular injections of 85 μg vaccine (with adjuvant) or placebo to the deltoid region of the arm at 0, 1, and 4 months, followed by two intranasal administrations of 30 μg unadjuvanted vaccine or placebo (one in each nostril) at months 4·5 and 5·0. The primary outcome was safety and the secondary outcome was humoral immunogenicity (anti-CTH522 IgG seroconversion). This study is registered with Clinicaltrials.gov, number NCT02787109. FINDINGS: Between Aug 15, 2016, and Feb 13, 2017, 35 women were randomly assigned (15 to CTH522:CAF01, 15 to CTH522:AH, and five to placebo). 32 (91%) received all five vaccinations and all participants were included in the intention-to-treat analyses. No related serious adverse reactions were reported, and the most frequent adverse events were mild local injection-site reactions, which were reported in all (15 [100%] of 15) participants in the two vaccine groups and in three (60%) of five participants in the placebo group (p=0·0526 for both comparisons). Intranasal vaccination was not associated with a higher frequency of related local reactions (reported in seven [47%]
Abraham S, Barton A, Eder L, et al., 2019, Advancing research paradigms and pathophysiological pathways in psoriatic arthritis and ankylosing spondylitis: Proceedings of the 2017 Platform for the Exchange of Expertise and Research (PEER) meeting, Seminars in Arthritis and Rheumatism, Vol: 48, Pages: 1005-1013, ISSN: 0049-0172
The seronegative spondyloarthropathies, including psoriatic arthritis (PsA) and ankylosing spondylitis (AS), are characterized by varied clinical symptoms, severity, and disease course , . Diagnosis and monitoring can be challenging because there is no definitive laboratory biomarker for reliably measuring inflammation or other disease processes associated with spondyloarthropathies. Over time, many patients with PsA and AS eventually experience significant disability and impaired quality of life , . This may be partially accounted for by delays in diagnosis and subsequent treatment , as well as the presence of comorbidities.In recent years, research efforts aimed at identifying risk factors for PsA, including clinical, imaging, genetic, and laboratory assessments, have yielded major advances. The Platform for the Exchange of Expertise and Research (PEER) was formed to facilitate the exchange of research insights, sharing of expertise, and discussion of unmet needs in rheumatology research.The objective of the current report is to provide an overview of the 2017 PEER meeting, which was held on May 19–20, 2017, in London, UK, and highlighted the most up-to-date research findings regarding PsA and AS pathophysiology, early detection, comorbidities, and treatment.
Woerner A, Pourmalek F, Panozzo C, et al., 2019, Acute aseptic arthritis: Case definition & guidelines for data collection, analysis, and presentation of immunisation safety data, VACCINE, Vol: 37, Pages: 384-391, ISSN: 0264-410X
Cheeseman HM, Day S, McFarlane LR, et al., 2018, Combined Skin and Muscle DNA Priming Provides Enhanced Humoral Responses to a Human Immunodeficency Virus Type 1 Clade C Envelope Vaccine, Human Gene Therapy, Vol: 29, Pages: 1011-1028, ISSN: 1043-0342
© Copyright 2018, Mary Ann Liebert, Inc., publishers2018. Intradermal (i.d.) and intramuscular (i.m.) injections when administered with or without electroporation (EP) have the potential to tailor the immune response to DNA vaccination. This Phase I randomized controlled clinical trial in human immunodeficiency virus type 1-negative volunteers investigated whether the site and mode of DNA vaccination influences the quality of induced cellular and humoral immune responses following the DNA priming phase and subsequent protein boost with recombinant clade C CN54 gp140. A strategy of concurrent i.d. and i.m. DNA immunizations administered with or without EP was adopted. Subtle differences were observed in the shaping of vaccine-induced virus-specific CD4+ and CD8+ T cell-mediated immune responses between groups receiving: i.d.EP+ i.m., i.d. + i.m.EP, and i.d.EP+ i.m.EPregimens. The DNA priming phase induced 100% seroconversion in all of the groups. A single, non-adjuvanted protein boost induced a rapid and profound increase in binding antibodies in all groups, with a trend for higher responses in i.d.EP+ i.m.EP. The magnitude of antigen-specific binding immunoglobulin G correlated with neutralization of closely matched clade C 93MW965 virus and Fc-dimer receptor binding (FcγRIIa and FcγRIIIa). These results offer new perspectives on the use of combined skin and muscle DNA immunization in priming humoral and cellular responses to recombinant protein.
Aggarwal D, Arumalla N, Jethwa H, et al., 2018, The use of biomarkers as a tool for novel psoriatic disease drug discovery, EXPERT OPINION ON DRUG DISCOVERY, Vol: 13, Pages: 875-887, ISSN: 1746-0441
Abraham SM, 2017, Pharmacogenomics- The scientific basis of rational drug development and prescribing., Journal of clinical and hospital pharmacy, ISSN: 0143-3180
“It is more important to know what sort of a patient has a disease than what sort of a disease a patient has” – (Hippocrates 460 BC- 370 BC)The holy grail of drug discovery is to ensure that an individual responds positively to an investigational drug with minimal or no adverse events. This could then translate to newly discovered drugs being licenced for prescribing as safe and effective therapeutics. Pharmacogenomics may herald the technology for this aspiration to become reality.Uniting the disciplines of pharmacology and genomics, pharmacogenomics provides a mechanism to understand and predict the response of an individual to a drug or group of drugs. This is based on the premise that an individual’s genotype affects the pharmacokinetics, pharmacodynamics and, ultimately, their response to a drug. This review will begin by reviewing the history of drug development and then proceed to discuss the use of pharmacogenomics in drug development through case studies in oncology, respiratory and vaccinology. It will then go on to discuss how pharmacogenomics presently influences prescribing practices and how this technology may have the potential to enhance patient safety when medicines are administered.
Lim AKP, Satchithananda K, Dick EA, et al., 2017, Microflow imaging: new Doppler technology to detect low-grade inflammation in patients with arthritis, European Radiology, Vol: 28, Pages: 1046-1053, ISSN: 0938-7994
AIM: To assess the efficacy of microvascular imaging in detecting low-grade inflammation in arthritis compared with Power Doppler ultrasound (PDUS). METHOD AND MATERIALS: Patients presenting for ultrasound with arthralgia were assessed with grey-scale, PDUS and Superb Microvascular Imaging (SMI). Videoclips were stored for analysis at a later date. Three musculoskeletal radiologists scored grey-scale changes, signal on PDUS and/or SMI within these joints. If a signal was detected on both PDUS and SMI, the readers graded the conspicuity of vascular signal from the two Doppler techniques using a visual analogue scale. RESULTS: Eighty-three patients were recruited with 134 small joints assessed. Eighty-nine of these demonstrated vascular flow with both PD and SMI, whilst in five no flow was detected. In 40 joints, vascularity was detected with SMI but not with PDUS (p = 0.007). Out of the 89 joints with vascularity on both SMI and PDUS, 23 were rated as being equal; while SMI scored moderately or markedly better in 45 cases (p <0.001). CONCLUSION: SMI is a new Doppler technique that increases conspicuity of Doppler vascularity in symptomatic joints when compared to PDUS. This allows detection of low grade inflammation not visualised with Power Doppler in patients with arthritis. KEY POINTS: • SMI detects vascularity with improved resolution and sensitivity compared to Power Doppler. • SMI can detect low-grade inflammation not seen with Power Doppler. • Earlier detection of active inflammation could have significant impact on treatment paradigms.
Coates LC, Abraham S, Tillett W, et al., 2017, Predictors of Long-Term Modified Minimal Disease Activity Response in Peripheral Spondyloarthritis Patients Treated with Adalimumab, 2017 ACR/ARHP Annual Meeting, Publisher: Wiley, Pages: 1560-1560, ISSN: 2326-5205
Urdaneta M, Jethwa H, Sultan R, et al., 2017, A review on golimumab in the treatment of psoriatic arthritis, Immunotherapy, Vol: 9, Pages: 871-888, ISSN: 1750-743X
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.
Coates LC, Abraham S, Tillett W, et al., 2017, PREDICTORS OF LONG-TERM MODIFIED MINIMAL DISEASE ACTIVITY RESPONSE IN PERIPHERAL SPONDYLOARTHRITIS PATIENTS TREATED WITH ADALIMUMAB, Annual European Congress of Rheumatology, Publisher: BMJ PUBLISHING GROUP, Pages: 668-669, ISSN: 0003-4967
packham J, Abraham S, 2017, A new era for collaboration?, Rheumatology, ISSN: 0080-2727
Ali O, Kakkar A, Abraham S, 2017, THE ASSOCIATION BETWEEN VITAMIN D STATUS AND INFLAMMATORY MARKERS IN PATIENTS WITH RHEUMATOID ARTHRITIS, Rheumatology Conference, Publisher: OXFORD UNIV PRESS, Pages: 123-123, ISSN: 1462-0324
Hull DN, Cooksley H, Chokshi S, et al., 2016, Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis, Arthritis Research and Therapy, Vol: 18, ISSN: 1478-6354
BackgroundAnti-TNF agents have revolutionised rheumatoid arthritis (RA) treatment; however, a third of patients fail to achieve therapeutic responses. Unexpectedly, studies in murine and human arthritis have indicated that anti-TNF treatment can increase circulating T helper 17 (Th17) cells, but the relationship to treatment response is unclear. To identify immune correlates of anti-TNF treatment response, we conducted a longitudinal study using clinical, ultrasound and T cell assessments.MethodsPatients with RA (n = 25) were studied at protocol visits during the initial 12 weeks of anti-TNF treatment. Improvement in the disease activity score of 28 joints (DAS28) >1.2 defined treatment responders (n = 16) and non-responders (n = 9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by grey scale and power Doppler ultrasound. The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)).ResultsThe frequency of circulating IL17-producing cells increased significantly 12 weeks after anti-TNF initiation (Elispot median (range) specific spot forming cells (spSFC)/106 360 (280–645) vs 632 (367 − 1167), p = 0.003). The increase in CD4 + IL17+ cells at 12 weeks was confirmed by FACS (median (range) %, 0.7 (0.5–0.9) vs 1.05 (0.6–1.3); p = 0.01). The increase in circulating Th17 cells inversely correlated with reduction in synovial vascularity (r = -0.68, p = 0.007) and thickening (r = -0.39; p = 0.04). Higher frequencies of circulating Th17 cells at baseline were associated with poorer anti-TNF treatment response defined by ultrasonographic measures.ConclusionsThese results demonstrate a link between changes in circulating Th17 cells
Abraham SM, 2016, The evidence for microbiome manipulation in inflammatory arthritis., Rheumatology, ISSN: 1462-0332
Coates LC, Abraham S, Tillett W, et al., 2016, PERFORMANCE OF MODIFIED MINIMAL DISEASE ACTIVITY (MDA) CRITERIA IN PATIENTS WITH PERIPHERAL SPONDYLOARTHRITIS: POST-HOC ANALYSIS OF ABILITY-2, CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, Vol: 34, Pages: 757-757, ISSN: 0392-856X
Coates LC, Abraham S, Tillett W, et al., 2016, THU0403 Performance of Modified Minimal Disease Activity (MDA) Criteria in Patients with Peripheral Spondyloarthritis: Post-Hoc Analysis of Ability-2, Annual European Congress of Rheumatology (EULAR), Publisher: BMJ Publishing Group, Pages: 334-334, ISSN: 0003-4967
Lythgoe MP, Abraham S, 2016, Good practice in shared care for inflammatory arthritis, British Journal of General Practice, Vol: 66, Pages: 275-277, ISSN: 1478-5242
Kirkham B, Helliwell P, McHugh N, et al., 2016, Are we optimising therapies in psoriatic arthritis? A survey of UK practice, Annual Meeting of the British Society for Rheumatology, Publisher: Oxford University Press, Pages: 138-139, ISSN: 1462-0332
Lythgoe M, Abraham S, 2016, Tacrolimus: an effective treatment in refractory psoriatic arthritis following biologic failure, Clinical and Experimental Rheumatology, Vol: 34, Pages: S12-S13, ISSN: 1593-098X
Liu NJ, Chapman R, Lin Y, et al., 2016, Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis., Nanoscale, Vol: 8, Pages: 4482-4485, ISSN: 2040-3372
Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.
Timmis A, Lenman M, Castagno S, et al., 2016, Knowledgebase and lifestyle choices in patients with psoriatic arthritis, Journal of Rheumatology, Vol: 43, Pages: 251-253, ISSN: 1499-2752
Sreerangaiah D, Grayer M, Fisher BA, et al., 2016, Quantitative power Doppler ultrasound measures of peripheral joint synovitis in poor prognosis early rheumatoid arthritis predict radiographic progression, Rheumatology, Vol: 55, Pages: 89-93, ISSN: 1462-0332
Objective. To assess the value of quantitative vascular imaging by power Doppler US (PDUS) as a tool that can be used to stratify patient risk of joint damage in early seropositive RA while still biologic naive but on synthetic DMARD treatment.Methods. Eighty-five patients with seropositive RA of <3 years duration had clinical, laboratory and imaging assessments at 0 and 12 months. Imaging assessments consisted of radiographs of the hands and feet, two-dimensional (2D) high-frequency and PDUS imaging of 10 MCP joints that were scored for erosions and vascularity and three-dimensional (3D) PDUS of MCP joints and wrists that were scored for vascularity.Results. Severe deterioration on radiographs and ultrasonography was seen in 45 and 28% of patients, respectively. The 3D power Doppler volume and 2D vascularity scores were the most useful US predictors of deterioration. These variables were modelled in two equations that estimate structural damage over 12 months. The equations had a sensitivity of 63.2% and specificity of 80.9% for predicting radiographic structural damage and a sensitivity of 54.2% and specificity of 96.7% for predicting structural damage on ultrasonography.Conclusion. In seropositive early RA, quantitative vascular imaging by PDUS has clinical utility in predicting which patients will derive benefit from early use of biologic therapy.
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