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Article ; Online: Annals of the Rheumatic Diseases collection on pregnancy 2018-2023: observational data-driven knowledge.

Duhig, Kate / Hyrich, Kimme L

2024

Abstract: 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 ... ...

Abstract	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. Therefore, observational research remains important for informing clinical practice and helping women with RMDs make decisions regarding their health preconception and during pregnancy. The Annals of the Rheumatic Diseases (ARD) continues to publish important research on pregnancy in RMDs to increase the evidence base on this subject. Here we present an overview of papers published on this topic between January 2018 and December 2023. Our focus includes papers on pregnancy and RMD outcome, the effects of drug exposure, fetal outcomes as well as fertility.
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2023-224861
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Article ; Online: EULAR 75-year anniversary: commentaries on

Hyrich, Kimme L

Annals of the rheumatic diseases

2022

Language	English
Publishing date	2022-09-14
Publishing country	England
Document type	Journal Article
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2022-222585
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Uh III Zs.114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Therapeutic advances in rheumatoid arthritis.

Brown, Philip / Pratt, Arthur G / Hyrich, Kimme L

BMJ (Clinical research ed.)

2024 Volume 384, Page(s) e070856

Abstract: Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid arthritis present with pain, swelling, and stiffness that typically affects symmetrically distributed small and large joints. Without ... ...

Abstract	Rheumatoid arthritis (RA) is one of the most common immune mediated inflammatory diseases. People with rheumatoid arthritis present with pain, swelling, and stiffness that typically affects symmetrically distributed small and large joints. Without effective treatment, significant joint damage, disability, and work loss develop, owing to chronic inflammation of the joint lining (synovium). Over the past 25 years, the management of this condition has been revolutionized, resulting in substantially higher levels of disease remission and better long term outcomes. This improvement reflects a paradigm shift towards early and aggressive pharmacological intervention coupled with a proliferation in treatment choice, in turn related to enhanced pathobiological understanding and the advent of new drugs for rheumatoid arthritis. Following an overview of these developments from a historical perspective, and with a general audience in mind, this review focuses on newer, targeted treatments in an ever evolving landscape. The review highlights ongoing areas of debate and unmet need, including the proportion of patients with persistent, difficult-to-treat disease, despite recent advances. Also discussed are personalized, strategic approaches to individual patients, the role for imaging in clinical decision making, and the goal of sustained, drug free remission and disease prevention in the future.
MeSH term(s)	Humans ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Inflammation ; Diagnostic Imaging ; Treatment Outcome ; Antirheumatic Agents/therapeutic use
Chemical Substances	Antirheumatic Agents
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj-2022-070856
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Article ; Online: Real world data in rheumatology.

Hyrich, Kimme L

Seminars in arthritis and rheumatism

2019 Volume 49, Issue 3S, Page(s) S22–S24

Abstract: Real world data plays an important role in rheumatology, allowing us to gain deeper insights into disease progression and treatment outcomes, including safety. It takes us beyond the conclusions of a clinical trial and allows us to "test" outcomes in an ... ...

Abstract	Real world data plays an important role in rheumatology, allowing us to gain deeper insights into disease progression and treatment outcomes, including safety. It takes us beyond the conclusions of a clinical trial and allows us to "test" outcomes in an uncontrolled, real-life environment. However, in order to generate trustworthy conclusions it is important that the provenance of and methodological considerations for handling real-world data are considered. This is increasingly true in this new era of big data, where not only the methods of handing such large datasets are critical, but also the ethics surrounding their collection and use. This overview summarises the key role real-world data has played in rheumatology, highlights key methodological challenges in analysing real-world data, and presents challenges for the future in order to continue to generate reliable scientific output using real-world data.
MeSH term(s)	Biomedical Research ; Disease Management ; Humans ; Rheumatic Diseases/therapy ; Rheumatology/instrumentation
Language	English
Publishing date	2019-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120247-9
ISSN	1532-866X ; 0049-0172
ISSN (online)	1532-866X
ISSN	0049-0172
DOI	10.1016/j.semarthrit.2019.09.021
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Zs.A 790: Show issues

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Article ; Online: The incidence and prevalence of Juvenile Idiopathic Arthritis differs between ethnic groups in England.

Beesley, Richard P / Hyrich, Kimme L / Humphreys, Jenny H

Rheumatology (Oxford, England)

2023

Abstract: Objectives: Juvenile Idiopathic Arthritis (JIA) is a heterogenous group of rare autoimmune disorders characterised by chronic joint inflammation of unknown aetiology with onset under 16years. Accurate estimates of disease rates help understand impacts ... ...

Abstract	Objectives: Juvenile Idiopathic Arthritis (JIA) is a heterogenous group of rare autoimmune disorders characterised by chronic joint inflammation of unknown aetiology with onset under 16years. 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. Methods: Data from the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record database in England, were used to estimate the incidence and prevalence of JIA by ethnic group amongst children and young people aged under 16 years between 2003 and 2018, with cases validated using Hospital Episode Statistics (HES). Chi square was used to test the difference in proportions compared to the ethnic distribution of England. Results: A total of 424 incident cases of JIA were identified, 389 validated using HES records. Incidence of JIA was higher amongst those of White ethnic group (6.2 per 100,000 population) compared to Mixed (3.0 per 100,000), Asian (2.7 per 100,000) and Black (2.9 per 100,000) communities. The ethnic group distribution of cases differed significantly compared to the general population (p < 0.0001). Conclusion: Incidence and prevalence of JIA differs between ethnic groups, and is different from the population. This is likely to be due to a combination of genetic and equity factors. Further research to understand the underlying cause of these differences is important, to enable targeted interventions and appropriate service provision.
Language	English
Publishing date	2023-12-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead700
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Zs.B 240: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 497: Show issues

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Article ; Online: How effective are JAK-inhibitors? Perspectives from clinical trials and real-world studies.

Lauper, Kim / Hyrich, Kimme L

Expert review of clinical immunology

2021 Volume 18, Issue 3, Page(s) 207–220

Abstract: Introduction: JAK-inhibitors have emerged as a new treatment option for rheumatoid arthritis, with five molecules currently available in different parts of the world: tofacitinib, baricitinib, upadacitinib, peficitinib, and filgotinib. These molecules ... ...

Abstract	Introduction: JAK-inhibitors have emerged as a new treatment option for rheumatoid arthritis, with five molecules currently available in different parts of the world: tofacitinib, baricitinib, upadacitinib, peficitinib, and filgotinib. These molecules have been the subject of numerous trials looking at their efficacy (how well they perform in controlled conditions) but also some observational studies from the general population to assess their effectiveness (how well treatment perform under real conditions). With each their own weaknesses and strengths, they give different but complementary information. Areas covered: We will review what we can learn from trials and real-world studies on how effective JAK-inhibitors are in the treatment of rheumatoid arthritis. Expert opinion: Trials of JAK-inhibitors have shown that JAK-inhibitors are efficacious for the treatment of rheumatoid arthritis. However, their main outcomes are not clinically meaningful as their aim is mainly the regulatory authorization of the product. Real-world studies are important as they evaluate the real-life effectiveness of the compounds, however, they are scarce at the moment, mainly evaluating tofacitinib and of variable quality. Future high-quality studies are needed to assess the real-world effectiveness of JAK-inhibitors in a more complete manner.
MeSH term(s)	Antirheumatic Agents/pharmacology ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Clinical Trials as Topic ; Humans ; Janus Kinase Inhibitors/therapeutic use ; Observational Studies as Topic
Chemical Substances	Antirheumatic Agents ; Janus Kinase Inhibitors
Language	English
Publishing date	2021-10-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2021.1982383
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Article ; Online: Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts.

Shoop-Worrall, Stephanie J W / Lawson-Tovey, Saskia / Wedderburn, Lucy R / Hyrich, Kimme L / Geifman, Nophar

EBioMedicine

2024 Volume 100, Page(s) 104946

Abstract: 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 ... ...

Abstract	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. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. Findings: The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Interpretation: Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. Funding: Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.
MeSH term(s)	Child ; Humans ; Adolescent ; Methotrexate/adverse effects ; Arthritis, Juvenile/drug therapy ; Prospective Studies ; Artificial Intelligence ; Antirheumatic Agents/adverse effects ; Machine Learning ; United Kingdom ; Treatment Outcome
Chemical Substances	Methotrexate (YL5FZ2Y5U1) ; Antirheumatic Agents
Language	English
Publishing date	2024-01-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104946
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Article ; Online: Rheumatic disease and COVID-19: epidemiology and outcomes.

Hyrich, Kimme L / Machado, Pedro M

Nature reviews. Rheumatology

2020 Volume 17, Issue 2, Page(s) 71–72

MeSH term(s)	Antirheumatic Agents/therapeutic use ; COVID-19/mortality ; Humans ; Rheumatic Diseases/complications ; Rheumatic Diseases/drug therapy
Chemical Substances	Antirheumatic Agents
Language	English
Publishing date	2020-12-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-020-00562-2
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Article ; Online: What can rheumatology expect from real-world data?

Hyrich, Kimme L / Zink, Angela

Rheumatology (Oxford, England)

2020 Volume 59, Issue 1, Page(s) 12–13

MeSH term(s)	Humans ; Pragmatic Clinical Trials as Topic ; Rheumatology
Language	English
Publishing date	2020-01-29
Publishing country	England
Document type	Introductory Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kez366
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Article ; Online: Comparative effectiveness of a second TNF inhibitor versus a non-TNF biologic in the treatment of polyarticular course juvenile idiopathic arthritis.

Mannion, Melissa L / Amin, Shahla / Balevic, Stephen / Chang, Min-Lee / Correll, Colleen K / Kearsley-Fleet, Lianne / Hyrich, Kimme L / Beukelman, Timothy

Arthritis care & research

2024

Abstract: Objective: The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non-TNFi biologic following discontinuation of a TNFi for patients with polyarticular-course juvenile idiopathic ... ...

Abstract	Objective: The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non-TNFi biologic following discontinuation of a TNFi for patients with polyarticular-course juvenile idiopathic arthritis (pJIA). Methods: Using the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, patients with pJIA who started a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on index date and a visit 6 months after the index date. Outcome measures included clinical juvenile arthritis disease activity score 10 (cJADAS10), cJADAS10 inactive disease (ID<2.5) and cJADAS10 minimal disease activity (MiDA<5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aOR) were calculated using propensity score quintiles to compare outcomes at 6 months following second biologic initiation. Results: There were 216 patients included, 84% initially received etanercept and most patients stopped it for ineffectiveness (74%). 183 (85%) started a second TNFi and 33 (15%) started a non-TNFi. Adalimumab was the most common second biologic (71% overall, 84% of second TNFi) and tocilizumab was the most common non-TNFi second biologic (9% overall, 58% of non-TNFi). There was no difference between TNFi and non-TNFi in cJADAS ID (29% versus 25%; aOR 1.23 [0.47-3.20]) or at least MiDA (43% versus 39%; aOR 1.11 [0.47-2.62]) at 6 months. Conclusion: Most patients with polyarticular course JIA started TNFi rather than non-TNFi as their second biologic, and there were no differences in disease activity at 6 months.
Language	English
Publishing date	2024-03-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.25339
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