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Article ; Online: Factors Associated With Treatment Pathways in Early Axial Spondyloarthritis: A Multistate Analysis of the 10-Year Follow-Up of the DESIR Cohort.

Portier, Elodie / Chevret, Sylvie / Walter-Petrich, Anouk / Ruyssen-Witrand, Adeline / Dougados, Maxime / Moltó, Anna

2024 Volume 51, Issue 4, Page(s) 368–377

Abstract: Objective: Current recommendations for the management of patients with axial spondyloarthritis (axSpA) emphasize the need of an individualized strategy in therapeutic decision-making. The study objectives were to describe therapeutic strategies observed ...

Abstract	Objective: Current recommendations for the management of patients with axial spondyloarthritis (axSpA) emphasize the need of an individualized strategy in therapeutic decision-making. The study objectives were to describe therapeutic strategies observed in axSpA, and to assess the factors associated with treatment intensification over time. Methods: We included patients with axSpA from the French prospective cohort DESIR ( Results: A total of 686/708 (96.9%) patients who had > 1 visit were analyzed. At cohort entry, 199 (29%) were untreated, 427 (62.2%) were receiving NSAIDs, 60 (8.7%) csDMARDs, and none were receiving TNFi. Over the follow-up period, patients mostly (46.4% of the time) received NSAIDs, followed by TNFi (24.4% of the time). The presence of sacroiliitis on radiographs, inflammatory bowel disease, and articular index were jointly associated with the transition to NSAIDs. Longer duration in the previous state often decreased the hazard of the transition to csDMARDs or TNFi. Worse disease activity outcomes increased the hazard of most transitions. Conclusion: To our knowledge, this was the first study using a multistate model to easily represent different treatment states, detailing the transitions across them and their associated factors. Different time profiles for the management of patients with axSpA were identified, including in those abstaining from treatment up to a significant proportion of patients treated with csDMARDs.
MeSH term(s)	Humans ; Prospective Studies ; Follow-Up Studies ; Spondylarthropathies ; Antirheumatic Agents/therapeutic use ; Axial Spondyloarthritis ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Spondylarthritis/drug therapy ; Spondylarthritis/complications
Chemical Substances	Antirheumatic Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Tumor Necrosis Factor Inhibitors
Language	English
Publishing date	2024-04-01
Publishing country	Canada
Document type	Journal Article
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.2023-0933
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Article ; Online: Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database.

Carlé, Caroline / Degboe, Yannick / Ruyssen-Witrand, Adeline / Arleevskaya, Marina I / Clavel, Cyril / Renaudineau, Yves

International journal of molecular sciences

2023 Volume 24, Issue 5

Abstract: T cells are known to be involved in the pathogenesis of rheumatoid arthritis (RA). Accordingly, and to better understand T cells' contribution to RA, a comprehensive review based on an analysis of the Immune Epitope Database (IEDB) was conducted. An ... ...

Abstract	T cells are known to be involved in the pathogenesis of rheumatoid arthritis (RA). Accordingly, and to better understand T cells' contribution to RA, a comprehensive review based on an analysis of the Immune Epitope Database (IEDB) was conducted. An immune CD8+ T cell senescence response is reported in RA and inflammatory diseases, which is driven by active viral antigens from latent viruses and cryptic self-apoptotic peptides. RA-associated pro-inflammatory CD4+ T cells are selected by MHC class II and immunodominant peptides, which are derived from molecular chaperones, host extra-cellular and cellular peptides that could be post-translationally modified (PTM), and bacterial cross-reactive peptides. A large panel of techniques have been used to characterize (auto)reactive T cells and RA-associated peptides with regards to their interaction with the MHC and TCR, capacity to enter the docking site of the shared epitope (DRB1-SE), capacity to induce T cell proliferation, capacity to select T cell subsets (Th1/Th17, Treg), and clinical contribution. Among docking DRB1-SE peptides, those with PTM expand autoreactive and high-affinity CD4+ memory T cells in RA patients with an active disease. Considering original therapeutic options in RA, mutated, or altered peptide ligands (APL) have been developed and are tested in clinical trials.
MeSH term(s)	Humans ; Epitopes ; Arthritis, Rheumatoid ; CD4-Positive T-Lymphocytes ; Peptides ; T-Lymphocyte Subsets ; HLA-DRB1 Chains
Chemical Substances	Epitopes ; Peptides ; HLA-DRB1 Chains
Language	English
Publishing date	2023-02-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24054296
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Article ; Online: Long-Term Association Between Disease Activity and Disability in Early Axial Spondyloarthritis: Results From a Prospective Observational Study of Inflammatory Back Pain.

Carvalho, Pedro D / Ruyssen-Witrand, Adeline / Marreiros, Ana / Machado, Pedro M

Arthritis care & research

2022 Volume 74, Issue 5, Page(s) 768–775

Abstract: Objective: Our primary objective was to study the long-term association between disease activity and disability in axial spondyloarthritis (SpA). Our secondary objective was to define patient profiles according to their level of disability.: Methods: ...

Abstract	Objective: Our primary objective was to study the long-term association between disease activity and disability in axial spondyloarthritis (SpA). Our secondary objective was to define patient profiles according to their level of disability. Methods: We analyzed data collected during the first 5 years of follow-up of a large early axial SpA cohort, the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. Multivariable models were built to study the association between the Health Assessment Questionnaire for Ankylosing Spondylitis (HAQ-AS) and the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), adjusting for potential confounders. Hierarchical multivariable analysis was conducted using the chi-square automatic interaction detector (CHAID) method, to help determine how variables best cluster to explain HAQ-AS. Results: Data from 644 patients and 5,152 visits were analyzed. HAQ-AS was longitudinally, independently, and positively associated with ASDAS-CRP (adjusted B [adjB] 0.205 [95% confidence interval (95% CI) 0.187, 0.222]), the enthesitis score (adjB 0.011 [95% CI 0.008, 0.015]), the Bath Ankylosing Spondylitis Metrology Index (adjB 0.087 [95% CI 0.069, 0.105]), and female sex (adjB 0.172 [95% CI 0.120, 0.225]). The CHAID decision tree revealed ASDAS-CRP as the first variable with discriminative power on HAQ-AS. The cutoffs that separated different patient disability profiles were obtained. Conclusion: Disease activity contributes longitudinally to disability and is hierarchically superior to any other variable in explaining this health domain. Enthesitis and spinal mobility are also key drivers of disability in early axial SpA. ASDAS-CRP cutoffs that separated different patient disability profiles largely mimicked the cutoffs previously defined for ASDAS-CRP disease activity states.
MeSH term(s)	Axial Spondyloarthritis ; Back Pain ; C-Reactive Protein/analysis ; Female ; Humans ; Severity of Illness Index ; Spondylarthritis/complications ; Spondylarthritis/diagnosis ; Spondylitis, Ankylosing/complications ; Spondylitis, Ankylosing/diagnosis
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2022-03-07
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	645059-3
ISSN	2151-4658 ; 0893-7524 ; 2151-464X
ISSN (online)	2151-4658
ISSN	0893-7524 ; 2151-464X
DOI	10.1002/acr.24515
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Article: Was trägt im Frühstadium einer axialen Spondyloarthritis zur Einschränkung der Wirbelsäulen- und Hüftgelenk-Beweglichkeit bei?

Carvalho, Pedro D. / Ruyssen-Witrand, Adeline

Morbus-Bechterew-Journal

2022 Volume 43, Issue 168, Page(s) 7

Language	German
Document type	Article
ZDB-ID	2119820-2
ISSN	1861-2105
Database	Current Contents Medicine

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Article: Repurposing the Fibrosis-4 Score in Rheumatoid Arthritis: Data from the ESPOIR Cohort.

Felten, Renaud / Fabacher, Thibaut / Sedmak, Nathanaël / Sibilia, Jean / Sordet, Christelle / Chatelus, Emmanuel / Berenbaum, Francis / Combe, Bernard / Ruyssen-Witrand, Adeline / Vittecoq, Olivier / Meyer, Nicolas / Gottenberg, Jacques-Eric

Journal of clinical medicine

2024 Volume 13, Issue 7

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2024-03-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13071905
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Article ; Online: Factors associated with drug-free remission at 5-year in early onset axial spondyloarthritis patients: Data from the DESIR cohort.

Ruyssen-Witrand, Adeline / Rousseau, Vanessa / Sommet, Agnès / Goupille, Philippe / Degboe, Yannick / Constantin, Arnaud

Joint bone spine

2022 Volume 89, Issue 4, Page(s) 105358

Abstract: Objectives: To assess the frequency of patients in drug-free remission at 5 years in a cohort of early axial SpA, and the factors associated with this remission.: Methods: Patients: patients included in the DESIR (DEvenir des Spondyloarthropathies ... ...

Abstract	Objectives: To assess the frequency of patients in drug-free remission at 5 years in a cohort of early axial SpA, and the factors associated with this remission. Methods: Patients: patients included in the DESIR (DEvenir des Spondyloarthropathies Indifférenciées Récentes) cohort undergoing the 5-year visit were selected for this analysis. Definition of 5-year drug-free remission: (1) all patients in ASAS partial remission and/or ASDAS<1.3 at 5 year visit and (2) taking no disease modifying anti-rheumatic drugs at the 5-year visit and (3) with an ASAS-NSAID score≤25 at the 5-year visit. Data analysis: the proportion of patients in drug-free remission was described. The association between demographic, clinical, biological and imaging characteristics and drug-free remission at 5 years was assessed by logistic regression. Results: Of the 412 patients included in this analysis, 73 (18%) were in drug-free remission at the 5-year visit. The baseline clinical factors associated with the chances to be in drug-free remission at the 5-year visit were symptom duration (OR=0.66 [95%CI%: 0.44-0.97]), lower HAQ-AS score (OR=0.32 [0.12-0.78]), lower ASDAS score (OR=0.55 [95%CI: 0.34-0.86]), ASAS-NSAID score (OR=0.91 [95%CI: 0.82-0.99]). Furthermore, anti-TNF use (OR=0.20 [95%CI: 0.08-0.42]) during the follow-up decreased the chances of being in 5-year drug-free remission. Conclusion: The probability of being in drug free remission at 5 year when beginning an axial SpA is low and is associated with lower baseline disease activity and functional scores, while starting an anti-TNF is associated with poor chances of later being in drug-free remission. NCT01648907.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Axial Spondyloarthritis ; Cohort Studies ; Humans ; Spondylarthritis/complications ; Spondylarthritis/diagnosis ; Spondylarthritis/drug therapy ; Spondylarthropathies/drug therapy ; Tumor Necrosis Factor Inhibitors
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Tumor Necrosis Factor Inhibitors
Language	English
Publishing date	2022-02-12
Publishing country	France
Document type	Clinical Study ; Journal Article
ZDB-ID	2020487-5
ISSN	1778-7254 ; 1297-319X
ISSN (online)	1778-7254
ISSN	1297-319X
DOI	10.1016/j.jbspin.2022.105358
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Article ; Online: Characteristics of the (Auto)Reactive T Cells in Rheumatoid Arthritis According to the Immune Epitope Database

Caroline Carlé / Yannick Degboe / Adeline Ruyssen-Witrand / Marina I. Arleevskaya / Cyril Clavel / Yves Renaudineau

International Journal of Molecular Sciences, Vol 24, Iss 4296, p

2023 Volume 4296

Abstract: T cells are known to be involved in the pathogenesis of rheumatoid arthritis (RA). Accordingly, and to better understand T cells’ contribution to RA, a comprehensive review based on an analysis of the Immune Epitope Database (IEDB) was conducted. An ... ...

Abstract	T cells are known to be involved in the pathogenesis of rheumatoid arthritis (RA). Accordingly, and to better understand T cells’ contribution to RA, a comprehensive review based on an analysis of the Immune Epitope Database (IEDB) was conducted. An immune CD8+ T cell senescence response is reported in RA and inflammatory diseases, which is driven by active viral antigens from latent viruses and cryptic self-apoptotic peptides. RA-associated pro-inflammatory CD4+ T cells are selected by MHC class II and immunodominant peptides, which are derived from molecular chaperones, host extra-cellular and cellular peptides that could be post-translationally modified (PTM), and bacterial cross-reactive peptides. A large panel of techniques have been used to characterize (auto)reactive T cells and RA-associated peptides with regards to their interaction with the MHC and TCR, capacity to enter the docking site of the shared epitope (DRB1-SE), capacity to induce T cell proliferation, capacity to select T cell subsets (Th1/Th17, Treg), and clinical contribution. Among docking DRB1-SE peptides, those with PTM expand autoreactive and high-affinity CD4+ memory T cells in RA patients with an active disease. Considering original therapeutic options in RA, mutated, or altered peptide ligands (APL) have been developed and are tested in clinical trials.
Keywords	rheumatoid arthritis ; memory T cells ; shared epitope ; neoepitopes ; peptides ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity.

Ruyssen-Witrand, Adeline / Guernec, Gregory / Dupont, Julia / Lapuyade, Diane / Lioté, Frédéric / Vittecoq, Olivier / Degboé, Yannick / Constantin, Arnaud

Arthritis research & therapy

2023 Volume 25, Issue 1, Page(s) 207

Abstract: Background: To compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA).: Methods: We included 256 patients from the ... ...

Abstract	Background: To compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA). Methods: We included 256 patients from the ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA and who were in sustained remission using the Simple Disease Activity Index (SDAI) score (n = 48), in sustained LDA (n = 139) or in sustained moderate to high disease activity (MDA or HDA, n = 69) over 10 years. The mTSSs progression over 10 years and the 10-year HAQ-DI scores were compared between the 3 groups. A longitudinal latent process mixed model was used to assess the independent effect of SDAI status over time on 10-year mTSS progression and HAQ-DI at 10 years. Results: Patients in sustained remission group were younger, had lower baseline HAQ-DI and mTSS scores and were less exposed to glucocorticoids, methotrexate or biologic disease-modifying anti-rheumatic drugs over 10 years. Patients in sustained remission had lower 10-year structural progression (variation of mTSS in the remission group: 4.06 (± 4.75) versus 14.59 (± 19.76) in the LDA group and 21.04 (± 24.08), p < 0.001 in the MDA or HDA groups) and lower 10-year HAQ-DI scores (10-year HAQ-DI in the remission group: 0.14 (± 0.33) versus 0.53 (± 0.49) in the LDA group and 1.20 (± 0.62) in the MDA or HDA groups, p < 0.001). The incidence of serious adverse events over 10 years was low, about 3.34/100 patient years, without any difference between the three groups. Conclusion: RA patients in sustained SDAI remission have better long-term structural and functional outcomes in comparison to patients in sustained LDA.
MeSH term(s)	Humans ; Arthritis, Rheumatoid/diagnostic imaging ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/epidemiology ; Methotrexate/therapeutic use ; Antirheumatic Agents/therapeutic use ; Prognosis ; Remission Induction ; Treatment Outcome ; Severity of Illness Index
Chemical Substances	Methotrexate (YL5FZ2Y5U1) ; Antirheumatic Agents
Language	English
Publishing date	2023-10-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-023-03176-7
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Article ; Online: Controversies in rheumatoid arthritis glucocorticoid therapy.

Ruyssen-Witrand, Adeline / Constantin, Arnaud

Joint bone spine

2017 Volume 85, Issue 4, Page(s) 417–422

Abstract: Despite therapeutic innovations in the past 20 years, glucocorticoids (GC) are still widely used for the symptomatic treatment of rheumatoid arthritis (RA). Studies have demonstrated the clinical and structural efficacy of moderate doses (i.e. 30-60 mg/d) ...

Abstract	Despite therapeutic innovations in the past 20 years, glucocorticoids (GC) are still widely used for the symptomatic treatment of rheumatoid arthritis (RA). Studies have demonstrated the clinical and structural efficacy of moderate doses (i.e. 30-60 mg/d) GC in addition to disease modifying anti-rheumatic drug (DMARD) initiation in early RA. A combination of a low dose of GC (i.e. 7.5-10 mg/d) and DMARDs increases remission rates and decreases the risk of medium-term structural progression in early RA. Intravenous and intramuscular administration of GC associated with DMARD initiation or intra-articular GC injections in symptomatic joints in tight control strategies increase remission rates in early RA. However, due to the risk of adverse events such as infections, cardiovascular events, or increased mortality induced by long-term use of GC, even at low-doses (e.g. 5 mg/d), GC should be prescribed at a minimal dose, for the shortest possible duration, and in association with DMARD initiation in early RA or DMARD change in active established RA.
MeSH term(s)	Adult ; Aged ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; France ; Glucocorticoids/administration & dosage ; Glucocorticoids/adverse effects ; Humans ; Injections, Intra-Articular ; Male ; Middle Aged ; Pain Measurement ; Patient Satisfaction/statistics & numerical data ; Prognosis ; Randomized Controlled Trials as Topic ; Range of Motion, Articular/drug effects ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; Glucocorticoids
Language	English
Publishing date	2017-12-12
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	2020487-5
ISSN	1778-7254 ; 1297-319X
ISSN (online)	1778-7254
ISSN	1297-319X
DOI	10.1016/j.jbspin.2017.12.002
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Article ; Online: Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

Bernard, Jessika / Barnetche, Thomas / Amory, Charlotte / Despres, Jerome / Vandersmissen, Maxime / Landrin, Justine / Gaujoux-Viala, Cecile / Lukas, Cédric / Ruyssen-Witrand, Adeline / Truchetet, Marie-Elise / Vergne-Salle, Pascale / Mathieu, Sylvain / Tournadre, Anne

RMD open

2024 Volume 10, Issue 1

Abstract: Objective: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA).: Methods: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with ... ...

Abstract	Objective: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). Methods: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). Conclusion: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.
MeSH term(s)	Humans ; Female ; Irritable Bowel Syndrome/complications ; Irritable Bowel Syndrome/epidemiology ; Cross-Sectional Studies ; Spondylitis, Ankylosing/complications ; Spondylarthritis/complications ; Spondylarthritis/epidemiology ; Biological Products
Chemical Substances	Biological Products
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Systematic Review ; Meta-Analysis ; Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003836
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