Publications by authors named "Kimme L Hyrich"

Objectives: The effect of the shared epitope (SE), and valine at position 11 (Val11) of HLA-DRB1, on the activation of CD4 T cells, is expected to be diminished by abatacept, a co-stimulation blocker. However, published evidence on the value of genetic stratification for abatacept treatment is conflicting. We aimed to compare the difference in effectiveness of abatacept and adalimumab in patients carrying the SE (or Val11).

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Objective: Our objective was to assess the incidence of major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA) treated with JAK inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), or biologic disease-modifying antirheumatic drugs with other modes of action (bDMARD-OMA) in a multicountry, real-world population.

Methods: Patients with RA from 15 registries in the JAK-pot collaboration were included. MACE incidence was analyzed using two approaches: a within-registry analysis aggregating country-specific estimates from registers with >25 incident MACEs through meta-analysis and an individual-level data combined analysis.

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Objectives: Tocilizumab is an IL-6 receptor humanized monoclonal antibody for the treatment of rheumatoid arthritis (RA) with intravenous (IV) and subcutaneous (SC) preparations available. Only IV tocilizumab is dosed adjusting for weight. Therefore, we aimed to study the association between body weight and the effectiveness of tocilizumab by the route of administration.

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Objectives: Multicategory prediction models (MPMs) can be used in health care when the primary outcome of interest has more than two categories. The application of MPMs is scarce, possibly due to added methodological complexities compared to binary outcome models. We provide a guide of how to develop, validate, and update clinical prediction models based on multinomial logistic regression.

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Objective: Juvenile idiopathic arthritis (JIA)-associated uveitis (JIAU) is a serious JIA comorbidity that can result in vision impairment. This study aimed to identify genetic risk factors within the major histocompatibility complex for JIAU and evaluate their contribution for improving risk classification when combined with clinical risk factors.

Methods: Data on single nucleotide polymorphisms, amino acids, and classical HLA alleles were available for 2,497 patients with JIA without uveitis and 579 patients with JIAU (female 2,060, male 1,015).

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Article Synopsis
  • The study examines how varying drug levels in patients with rheumatoid arthritis can affect the effectiveness of adalimumab and etanercept biosimilars and whether dosing schedules can be adjusted for better results.! -
  • Researchers used population pharmacokinetic (popPK) modeling and simulation to analyze drug concentrations in patients and found that dosing intervals could potentially be modified to reach therapeutic drug levels more quickly.! -
  • Simulation results suggested that administering the etanercept biosimilar every 10 days could achieve steady-state drug concentrations faster than the standard 7-day interval, paving the way for personalized dosing strategies that could improve treatment efficacy and reduce costs.!
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Article Synopsis
  • The study focused on children and young people with juvenile idiopathic arthritis (JIA) who were switched from anti-TNF biological originators to biosimilars for non-medical reasons, assessing their drug survival and disease activity over 6 months.
  • It involved 224 patients, with a significant majority transitioning from adalimumab, etanercept, or infliximab, and a matched cohort of 164 patients who continued on the originator was analyzed using a Cox proportional hazard model.
  • The findings indicated that switching to biosimilars did not lead to a higher likelihood of stopping treatment compared to those who remained on the originator, suggesting similar persistence of the medication between the two groups.
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Objectives: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs).

Methods: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors.

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Background: Exercise and physical activity are key components of management in patients with rheumatic musculoskeletal diseases (RMD), but people of the South Asian communities have a lower level of engagement with these activities compared to their Caucasian counterparts. The aim of this qualitative systematic review was to determine the barriers and facilitators of exercise and physical activity in South Asian communities who have migrated and live in western countries, particularly in those who have RMD.

Methods: Qualitative studies, published in English between 1999 and 2021 and including evaluation of barriers and/or facilitators to exercise or physical activity behaviour in people of South Asian adult communities who have migrated and/or lived in western countries were identified from Embase, MEDLINE, CINAHL, PsycINFO, Google Scholar and manual searches.

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Objective: Janus kinase inhibitors (JAKis) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) effectively treat rheumatoid arthritis (RA). However, due to safety concerns, the European Medicines Agency (EMA) published risk-minimization measures limiting JAKi prescription to certain at-risk patients unless no suitable alternative is available. This analysis included patients who had started their first-ever JAKi (before EMA measures were published) in a large national cohort study to investigate the potential impact of these measures on JAKi prescribing and utilization in the UK.

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Article Synopsis
  • The study aimed to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non-TNFi biologic in children with polyarticular-course juvenile idiopathic arthritis (pJIA) after discontinuing the first TNFi due to ineffectiveness.
  • 216 patients were analyzed, with 85% starting a second TNFi, and the most common biologic switches being adalimumab for TNFi and tocilizumab for non-TNFi.
  • Results showed no significant differences in disease activity after six months, suggesting that both treatment options may be equally effective for managing pJIA.
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Background: Exercise and physical activity (EPA) are recommended for people with chronic musculoskeletal disease; however, lower levels of engagement with EPA has been consistently reported in people from the South Asian community across a range of diseases. As language can pose a significant barrier in healthcare, this study aimed to understand the enablers and barriers to the acceptance of EPA among non-English speaking South Asian people who attended rheumatology clinics.

Methods: 12 non-English speaking individuals from the South Asian community who had chronic musculoskeletal disease with significant pain scores were interviewed via telephone or face-to-face in their spoken languages.

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Pregnancy can be an exciting time but for those living with rheumatic musculoskeletal diseases (RMDs), it can also be a time fraught with concern, including what effect pregnancy will have on the underlying RMD and what effect the RMD may have on the pregnancy and the baby, including the effects of medications. Generating an evidence base in pregnancy is challenging. Few interventional trials of medications in RMD pregnancies have ever been conducted, often for concerns of safety for both the mother and the child.

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Article Synopsis
  • Rheumatoid arthritis (RA) is a prevalent immune-mediated inflammatory disease causing joint pain, swelling, and stiffness, leading to potential long-term damage if untreated.
  • The management of RA has significantly improved over the last 25 years, focusing on early and aggressive treatment strategies and the introduction of new medications.
  • The review also addresses ongoing challenges in treatment, including patients with hard-to-treat cases, and emphasizes the need for personalized treatment approaches and the goal of achieving drug-free remission in the future.
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Objective: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA).

Methods: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort.

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Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures.

Methods: Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium.

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Objectives: JIA is a heterogeneous group of rare autoimmune disorders characterized by chronic joint inflammation of unknown aetiology with onset under 16 years. Accurate estimates of disease rates help understand impacts on individuals and society, and provide evidence for health service planning and delivery. This study aimed to produce the first national estimates of incidence and prevalence by ethnic group using electronic health records.

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Objectives: In rheumatology, there is a clinical need to identify patients at high risk (>50%) of not responding to the first-line therapy methotrexate (MTX) due to lack of disease control or discontinuation due to adverse events (AEs). Despite this need, previous prediction models in this context are at high risk of bias and ignore AEs. Our objectives were to (i) develop a multinomial model for outcomes of low disease activity and discontinuing due to AEs 6 months after starting MTX, (ii) update prognosis 3-month following treatment initiation, and (iii) externally validate these models.

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Article Synopsis
  • In a clinical trial, patients with rheumatoid arthritis using the Janus kinase inhibitor tofacitinib experienced higher rates of adverse events compared to those on TNF inhibitors like adalimumab or etanercept.
  • A study aimed to analyze treatment discontinuations due to adverse events among JAK inhibitors, TNF inhibitors, and other biological therapies in a real-world setting involving over 46,000 treatment courses.
  • Results indicated that the rate of treatment discontinuation was similar for TNF inhibitors and JAK inhibitors overall, but certain JAK inhibitors showed different patterns, especially with older patients and specific cardiovascular risk factors, warranting cautious interpretation of the findings.
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Objectives: Epidemiological estimates of psoriatic arthritis (PsA) underpin the provision of healthcare, research, and the work of government, charities and patient organizations. Methodological problems impacting prior estimates include small sample sizes, incomplete case ascertainment, and representativeness. We developed a statistical modelling strategy to provide contemporary prevalence and incidence estimates of PsA from 1991 to 2020 in the UK.

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Article Synopsis
  • This study looked at how serious infections and tuberculosis (TB) happen in patients with rheumatoid arthritis (RA) who are taking different medications.
  • They analyzed data from nearly 34,000 treatment cases over 3 years to see how often these problems occurred with each type of medicine.
  • The results showed that serious infections were a bit more common with certain medications, and TB mostly happened when patients were on early treatments before 2009.
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Objectives: Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (i) drug survival and (ii) disease activity at 6 months and 12 months, compared with those who remain on the originator.

Methods: Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving the originator, based on gender, age, disease duration and originator start year.

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