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Article ; Online: Abatacept in individuals with autoantibody-positive arthralgia at risk for rheumatoid arthritis.

2024 Volume 403, Issue 10429, Page(s) 785–787

MeSH term(s)	Humans ; Abatacept/adverse effects ; Arthritis, Rheumatoid/drug therapy
Chemical Substances	Abatacept (7D0YB67S97)
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(24)00055-2
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Article ; Online: Preventive interventions in individuals at risk for Rheumatoid Arthritis: State of the art and perspectives.

Van der Helm-van Mil, Annette H M

Joint bone spine

2023 Volume 90, Issue 4, Page(s) 105543

Abstract: During the last decade, the outlook for patients with rheumatoid arthritis (RA) has improved greatly, especially for patients with autoantibody-positive RA. To further improve long-term disease outcomes, the field has turned to investigating the efficacy ...

Abstract	During the last decade, the outlook for patients with rheumatoid arthritis (RA) has improved greatly, especially for patients with autoantibody-positive RA. To further improve long-term disease outcomes, the field has turned to investigating the efficacy of treatment initiated in the pre-arthritic phase of RA, based on the adage "the sooner the better." In this review, the concept of prevention is evaluated and different risk stages are being examined for their pre-test risks of RA development. These risks affect the post-test risk of biomarkers used at these stages and, consequently, the accuracy with which the risk of RA can be estimated. Furthermore, through their effect on accurate risk stratification, these pre-test risks ultimately also associate with the likelihood of false-negative trial results (the so-called "clinicostatistical tragedy"). Outcome measures to assess preventive effects are evaluated and relate to either the occurrence of disease itself or to the severity of risk factors for RA development. Results of recently completed prevention studies are discussed in the light of these theoretical considerations. The results vary, but clear prevention of RA has not been demonstrated. While some treatments (e.g. methotrexate) persistently reduced symptom severity, physical disability, and the severity of imaging joint inflammation, other treatments were not reported to produce long-lasting effects (hydroxychloroquine, rituximab, atorvastatin). The review concludes with future perspectives regarding the design of new prevention studies and considerations and requirements before findings can be implemented in daily practice in individuals at risk of RA attending rheumatology practices.
MeSH term(s)	Humans ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/prevention & control ; Methotrexate/therapeutic use ; Risk Factors ; Autoantibodies ; Rituximab
Chemical Substances	Methotrexate (YL5FZ2Y5U1) ; Autoantibodies ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2023-02-15
Publishing country	France
Document type	Review ; Journal Article
ZDB-ID	2020487-5
ISSN	1778-7254 ; 1297-319X
ISSN (online)	1778-7254
ISSN	1297-319X
DOI	10.1016/j.jbspin.2023.105543
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Article ; Online: Specificity of hand MRI in arthralgia suspicious for progression to RA; what is the risk of overdiagnosis?

Ton, Dennis A / van der Helm-van Mil, Annette H M

Joint bone spine

2023 Volume 91, Issue 2, Page(s) 105648

MeSH term(s)	Humans ; Overdiagnosis ; Hand ; Arthralgia/diagnostic imaging ; Arthralgia/etiology ; Magnetic Resonance Imaging ; Disease Progression
Language	English
Publishing date	2023-10-04
Publishing country	France
Document type	Editorial
ZDB-ID	2020487-5
ISSN	1778-7254 ; 1297-319X
ISSN (online)	1778-7254
ISSN	1297-319X
DOI	10.1016/j.jbspin.2023.105648
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Article ; Online: Is tooth extraction as proxy for periodontal disease related to the development of RA? Lessons from a longitudinal study in the at-risk stage of clinically suspect arthralgia.

Khidir, Sarah J H / Toes, René E M / van Mulligen, Elise / van der Helm-van Mil, Annette H M

Annals of the rheumatic diseases

2024

Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Letter
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/ard-2024-225688
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Article ; Online: Deep learning in rheumatological image interpretation.

Stoel, Berend C / Staring, Marius / Reijnierse, Monique / van der Helm-van Mil, Annette H M

Nature reviews. Rheumatology

2024 Volume 20, Issue 3, Page(s) 182–195

Abstract: Artificial intelligence techniques, specifically deep learning, have already affected daily life in a wide range of areas. Likewise, initial applications have been explored in rheumatology. Deep learning might not easily surpass the accuracy of classic ... ...

Abstract	Artificial intelligence techniques, specifically deep learning, have already affected daily life in a wide range of areas. Likewise, initial applications have been explored in rheumatology. Deep learning might not easily surpass the accuracy of classic techniques when performing classification or regression on low-dimensional numerical data. With images as input, however, deep learning has become so successful that it has already outperformed the majority of conventional image-processing techniques developed during the past 50 years. As with any new imaging technology, rheumatologists and radiologists need to consider adapting their arsenal of diagnostic, prognostic and monitoring tools, and even their clinical role and collaborations. This adaptation requires a basic understanding of the technical background of deep learning, to efficiently utilize its benefits but also to recognize its drawbacks and pitfalls, as blindly relying on deep learning might be at odds with its capabilities. To facilitate such an understanding, it is necessary to provide an overview of deep-learning techniques for automatic image analysis in detecting, quantifying, predicting and monitoring rheumatic diseases, and of currently published deep-learning applications in radiological imaging for rheumatology, with critical assessment of possible limitations, errors and confounders, and conceivable consequences for rheumatologists and radiologists in clinical practice.
MeSH term(s)	Humans ; Deep Learning ; Artificial Intelligence ; Rheumatology ; Diagnostic Imaging ; Rheumatic Diseases/diagnostic imaging
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-023-01074-5
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Article ; Online: Grip strength reduction in clinically suspect arthralgia: natural trajectories and improvement after treatment.

Krijbolder, Doortje I / Wouters, Fenne / Niemantsverdriet, Ellis / van der Helm-van Mil, Annette H M

RMD open

2023 Volume 9, Issue 2

MeSH term(s)	Humans ; Arthralgia ; Hand Strength
Language	English
Publishing date	2023-05-21
Publishing country	England
Document type	Letter
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003110
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Article ; Online: Exploratory analysis of the TREAT EARLIER trial: is the efficacy of temporary methotrexate treatment dose-dependent?

Krijbolder, Doortje I / Boom, Hido D / van der Helm-van Mil, Annette H M

The Lancet. Rheumatology

2023 Volume 5, Issue 8, Page(s) e437–e439

MeSH term(s)	Methotrexate/therapeutic use ; Humans ; Clinical Trials as Topic
Chemical Substances	Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(23)00164-9
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Article ; Online: Responsiveness and sensitivity of PROMs to change in disease activity status in early and established rheumatoid arthritis.

Looijen, Agnes E M / van Mulligen, Elise / Vonkeman, Harald E / van der Helm-van Mil, Annette H M / de Jong, Pascal H P

Rheumatology (Oxford, England)

2024

Abstract: Objectives: To determine whether patient reported outcome measures (PROMs) capturing activity limitations, health impact, pain, fatigue and work ability are responsive and sensitive to changes in disease activity status in patients with early and ... ...

Abstract	Objectives: To determine whether patient reported outcome measures (PROMs) capturing activity limitations, health impact, pain, fatigue and work ability are responsive and sensitive to changes in disease activity status in patients with early and established rheumatoid arthritis (RA). Methods: All early RA patients (n = 557) from the tREACH-trial and established RA patients (n = 188) from the TARA-trial were included. Both studies were multicentre, single-blinded trials with a treat-to-target management approach. The following PROMs were studied: Health Assessment Questionnaire Disability Index(HAQ-DI), morning stiffness severity, EQ-5D, general health, 36-item short form(SF-36), joint pain, fatigue and productivity loss. Mean changes in PROMs between two consecutive visits were compared with changes in disease activity status(remission, low disease activity and active disease) using linear mixed models and standardised response means. Additionally, the proportion of individual observations that showed an expected PROM response to disease activity status alterations was calculated. Results: HAQ-DI, morning stiffness severity, general health, EQ-5D and joint pain demonstrated responsiveness to improvement or worsening of disease activity status in both early and established RA. SF-36 physical and mental component scale, fatigue and productivity loss did not show this effect in both groups. Across nearly all PROMs, the magnitude of change and the proportion of individual observations that reflect a shift from and to active disease remained low. Conclusion: HAQ-DI, morning stiffness severity, EQ-5D, general health and joint pain are responsive to disease activity status alterations on a group level in both early and established RA. For the individual patient the responsiveness of these PROMs is poor. Clinical trial registration: tREACH trial (www.isrctn.com, ISRCTN26791028) and TARA trial (www.onderzoekmetmensen.nl, NTR2754).
Language	English
Publishing date	2024-04-04
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/keae213
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Article ; Online: Work-related physical strain and development of joint inflammation in the trajectory of emerging inflammatory and rheumatoid arthritis: a prospective cohort study.

van Dijk, Bastiaan T / Boeren, Anna M P / Khidir, Sarah J H / den Hollander, Nikolet K / van der Helm-van Mil, Annette H M

RMD open

2024 Volume 10, Issue 2

Abstract: Objectives: Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently understood. We hypothesised that mechanical stress/physical ... ...

Abstract	Objectives: Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently understood. We hypothesised that mechanical stress/physical strain is a risk factor for joint inflammation in RA. Therefore, we studied work-related physical strain in subjects with clinically suspected arthralgia (CSA) as a risk factor for the presence of imaging-detected subclinical joint inflammation and the development of clinical arthritis/RA. Methods: In 501 CSA patients and 155 symptom-free persons' occupation-related physical strain was quantified using the International Standard Classification of Occupations. Contrast-enhanced hand-MRIs were made and evaluated for joint inflammation (sum of synovitis/tenosynovitis/osteitis). CSA patients were followed on RA development. Age relationship was studied using an interaction term of physical strain with age. Results: The degree of physical strain in CSA is associated with the severity of joint inflammation, independent of educational-level/BMI/smoking (interaction physical strain-age p=0.007; indicating a stronger association with increasing age). Physical strain is associated with higher tenosynovitis scores, in particular. In symptom-free persons, physical strain was not associated with imaging-detected joint inflammation. Higher degrees of physical strain also associated with higher risks for RA development in an age-dependent manner (HR=1.20 (1.06-1.37)/10-year increase in age), independent of educational-level/BMI/smoking. This association was partly mediated by an effect via subclinical joint inflammation. Conclusions: Work-related physical strain increases the risk of subclinical joint inflammation and of developing RA. The age relationship suggests an effect of long-term stress or that tenosynovium is more sensitive to stress at older age. Together, the data indicate that mechanical stress contributes to the development of arthritis in RA.
MeSH term(s)	Humans ; Tenosynovitis/complications ; Prospective Studies ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/epidemiology ; Synovitis/etiology ; Arthralgia/etiology ; Inflammation
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003895
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Article ; Online: Patient burden and joint-inflammation during development of RA from arthralgia: is it similar in ACPA-positive and ACPA-negative disease?

Khidir, Sarah J H / Krijbolder, Doortje I / Glas, Herman K / van Mulligen, Elise / van der Helm-van Mil, Annette H M

Rheumatology (Oxford, England)

2024

Abstract: Objectives: Anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative rheumatoid arthritis(RA) differ in underlying risk factors but have a similar clinical presentation at RA-diagnosis. It is unknown what the ACPA-associated differences or ... ...

Abstract	Objectives: Anti-citrullinated protein antibody(ACPA)-positive and ACPA-negative rheumatoid arthritis(RA) differ in underlying risk factors but have a similar clinical presentation at RA-diagnosis. It is unknown what the ACPA-associated differences or similarities are during the symptomatic at-risk stage of RA, clinically suspect arthralgia(CSA). To deepen insights into these differences/similarities, we compared the course of symptoms/impairments and subclinical joint-inflammation in the CSA-phase during progression to inflammatory arthritis(IA) or to CSA-resolution. Methods: 845 CSA-patients were followed for median 24 months; 136 patients developed IA and additional 355/505 patients had resolution of CSA according to rheumatologists. Patient burden (pain/morning stiffness/fatigue/functional disabilities/presenteeism) was assessed at baseline, 4/12/24 months and IA-development. Subclinical joint-inflammation in hands/feet was assessed over time with 1.5 T-MRI. Linear/Poisson mixed models were used. Results: Both in ACPA-positive and ACPA-negative patients, patient burden increased towards IA-development and decreased towards CSA-resolution. However, patient burden was lower in ACPA-positive than ACPA-negative disease on all timepoints. Conversely, subclinical joint-inflammation tended to increase more rapidly during development of ACPA-positive IA (IRR = 1.52,95%CI = 0.94-2.47, p= 0.089), and remained higher over time in ACPA-positive CSA-patients achieving resolution compared with ACPA-negative patients (IRR = 1.52,95%CI = 1.07-2.15, p= 0.018). Although correlation coefficients between changes in patient burden and subclinical joint-inflammation during progression to IA were weak, they were consistently higher in ACPA-positive than ACPA-negative disease, e.g. ρ = 0.29 vs ρ = 0.12 for functional disabilities. Conclusion: During RA-development and CSA-resolution, ACPA-positive CSA-patients have lower patient burden, but more subclinical joint-inflammation than ACPA-negative CSA-patients. These data strengthen the notion that the development of ACPA-positive and ACPA-negative RA is pathophysiologically different, and encourage further research on these differences.
Language	English
Publishing date	2024-01-23
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/keae044
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