Data from the DESIR cohort

Funding: g Devenir des Spondyloarthropathies Indifférenciées Récentes (DESIR) is financially supported by an unrestricted grant from Pfizer. AS is supported by a doctoral grant from 'Fundação para a Ciência e Tecnologia' (SFRH/ BD/108246/2015). The DESIR study is conducted as a Programme Hospitalier de Recherche Clinique with Assistance Publique Hopitaux de Paris as the sponsor. The DESIR study is also under the umbrella of the French Society of Rheumatology, which financially supports the cohort. An unrestricted grant from Pfizer as been allocated for the first 10 years.Objective To study changes on MRI of the spine and sacroiliac joint (SIJ) in early axial spondyloarthritis (axSpA) over time. Methods In the Devenir des Spondyloarthropathies Indifférenciées Récentes cohort, MRI-spine and MRI-SIJ at baseline and 2 and 5 years were scored by central readers for bone marrow oedema (BME), fatty lesions, erosions, sclerosis, ankylosis and spinal bone spurs. The average mean number of lesions was reported or the agreement of ≥2 out of 3 readers for binary outcomes. Net progression was calculated by subtracting the patients that a € improved' from those that a € worsened' divided by the total number of patients. Results Over 5 years, in 155 patients with axSpA (mean age 33.5 (SD 8.9) years, symptom duration 1.4 (0.8) years, 63% human leucocyte antigen+, 14% modified New York+), BME on MRI-SIJ decreased by a mean Spondyloarthritis Research Consortium of Canada score of 1.4 (SD 6.5) (p=0.009). The largest BME decrease was observed in patients using biological disease-modifying antirheumatic drugs at 5 years. Spinal BME increased by 0.3 (4.6) (p=0.41). Fatty lesions and/or erosions on MRI-SIJ increased by a mean of 1.0 (SD 2.6) (p<0.001). Spinal fatty lesions and/or erosions increased by 0.2 (SD 0.5) (p<0.001). Compared with baseline, at 5 years, 7.3% less patients had BME on MRI-SIJ according to the Assessment of Spondyloarthritis International Society definition, while 6.6% more patients had ≥5 fatty lesions and/or erosions. At 5 years, 0.7% less patients had ≥5 spinal BME lesions and 0.7% less patients had ≥5 spinal fatty lesions. Conclusion Over 5 years, BME on MRI-SIJ decreased and spinal BME remained similar, but numerically, little progression of structural lesions on MRI of the SIJ and spine was seen.publishersversionpublishe

Mesenchymal stem cells at the intersection of cell and gene therapy

Mesenchymal stem cells have the ability to differentiate into osteoblasts, chondrocytes and adipocytes. Along with differentiation, MSCs can modulate inflammation, home to damaged tissues and secret bioactive molecules. These properties can be enhanced through genetic-modification that would combine the best of both cell and gene therapy fields to treat monogenic and multigenic diseases

Translating patient reported outcome measures: Methodological issues explored using cognitive interviewing with three rheumatoid arthritis measures in six European languages

© The Author 2016. Objective. Cross-cultural translation of patient-reported outcome measures (PROMs) is a lengthy process, often performed professionally. Cognitive interviewing assesses patient comprehension of PROMs. The objective was to evaluate the usefulness of cognitive interviewing to assess translations and compare professional (full) with non-professional (simplified) translation processes. Methods. A full protocol used for the Bristol RA Fatigue Multi-dimensional Questionnaire and Numerical Rating Scale (BRAF-MDQ, BRAF-NRS) was compared with a simplified protocol used for the RA Impact of Disease scale (RAID). RA patients in the UK, France, the Netherlands, Germany, Spain and Sweden completed the PROMs during cognitive interviewing (BRAFs in the UK were omitted as these were performed during development). Transcripts were deductively analysed for understanding, information retrieval, judgement and response options. Usefulness of cognitive interviewing was assessed by the nature of problems identified, and translation processes by percentage of consistently problematic items (≥40% patients per country with similar concerns). Results. Sixty patients participated (72% women). For the BRAFs (full protocol) one problematic item was identified (of 23 items × 5 languages, 1/115 = 0.9%). For the RAID (simplified protocol) two problematic items were identified (of 7 items × 6 languages, 2/42 = 4.8%), of which one was revised (Dutch). Coping questions were problematic in both PROMs. Conclusion. Conceptual and cultural challenges though rare were important, as identified by formal evaluation, demonstrating that cognitive interviewing is crucial in PROM translations. Proportionately fewer problematic items were found for the full than for the simplified translation procedure, suggesting that while both are acceptable, professional PROM translation might be preferable. Coping may be a particularly challenging notion cross-culturally

Use of glycol chitosan modified by 5β-cholanic acid nanoparticles for the sustained release of proteins during murine embryonic limb skeletogenesis

Murine embryonic limb cultures have invaluable roles in studying skeletogenesis. Substance delivery is an underdeveloped area in developmental biology that has primarily relied on Affi-Gel-Blue-Agarose-beads. However, the lack of information about the efficiency of agarose-bead loading and release and difficulties for a single-bead implantation represent significant limitations. We optimized the use of glycol-chitosan–5β-cholanic-acid-conjugates (HGC) as a novel protein delivery system in mouse embryonic limbs. To this purpose, we loaded HGC either with recombinant Noggin, or bovine serum albumin (BSA). The size, morphology and stability of the protein-loaded-HGC were determined by transmission-electron-microscopy and dynamic-light-scattering. HGC-BSA and HGC-Noggin loading efficiencies were 80-90%. Time-course study revealed that Noggin and BSA were 80-90% of released after 48-hours. We developed several techniques to implant protein-loaded-HGC into murine embryonic joints from embryonic age (E)13.5 to E15.5, including a micro-injection system dispensing nanoliters. HGC did not interfere with skeletogenesis. Using CBR-3BA staining, we detected HGC-nanoparticles within implanted tissues. Furthermore, a sustained release of BSA and Noggin was demonstrated in HGC-BSA and HGC-Noggin injected regions. HGC-released Noggin was biologically active in blocking the BMP signaling in in vitro mesenchyme limb micromasses as well as in ex-vivo limb cultures. Results reveal that HGC is a valuable protein-delivery system in developmental biology

Sex differential impact of comorbidities in spondyloarthritis : data from COMOSPA study

To describe and compare the prevalence of comorbidities in female and male patients with spondyloarthritis (SpA) and to assess whether comorbidities had a different impact on disease outcomes in male and female patients. This is a post hoc analysis of the COMOrbidities in SPondyloArthritis study. Differences in comorbidities regarding sex were assessed using logistic regression models. Comorbidities were evaluated for their impact on disease outcomes (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index, European health-related quality of life questionnaire) with linear models, which included sex and comorbidity as explanatory variables and their interaction. Age and treatment with biological synthetic disease-modifying antirheumatic drugs were included as confounders. We included 3982 patients with SpA (65% male, mean age 43.6 years). Male and female patients with SpA exhibited similar comorbidity profiles, except for a low prevalence of fibromyalgia in males and a higher prevalence of certain cardiovascular risk factors in males (hypertension, dyslipidaemia, renal impairment and ischaemic heart disease). Comorbidities, especially fibromyalgia, correlated with higher disease activity, decreased physical function and reduced health-related quality of life in both sexes. Some comorbidities exhibited sex-specific associations with disease outcomes. Peptic ulcers and high waist circumference had a greater impact on disease activity in females (with a higher impact in BASDAI than in ASDAS). In contrast, osteoporosis had a more pronounced effect on physical function in male patients. Comorbidities exert distinct influences on disease activity, physical function and health-related quality of life in male and female patients with SpA. Understanding these sex-specific effects is crucial for improving SpA management, emphasising the importance of assessing disease activity using ASDAS when comorbidities are present to mitigate sex-related disparities in disease assessment

The 5-year data of the DESIR cohort

Funding Information: Acknowledgements the dESIr cohort was sponsored by the département de la recherche Clinique et du développement de l’Assistance publique–Hôpitaux de paris. this study is conducted under the umbrella of the French Society of rheumatology and InSErM (Institut national de la Santé et de la recherche Médicale). the database management is performed within the department of epidemiology and biostatistics (professor paul Landais, d.I.M., nîmes, France). An unrestricted grant from pfizer was allocated for the 10 years of the follow-up of the recruited patients. the authors would like to thank the different regional participating centres: pr Maxime dougados (paris – Cochin B), pr André Kahan (paris - Cochin A), pr olivier Meyer (paris - Bichat), pr pierre Bourgeois (paris - La pitié Salpetrière), pr Francis Berenbaum (paris - Saint Antoine), pr pascal Claudepierre (Créteil), pr Maxime Breban (Boulogne Billancourt), dr Bernadette Saint-Marcoux (Aulnay-sous-Bois), pr philippe Goupille (tours), pr Jean-Francis Maillefert (dijon), dr xavier puéchal, dr Emmanuel dernis (Le Mans), pr daniel Wendling (Besançon), pr Bernard Combe (Montpellier), pr Liana Euller-Ziegler (nice), pr philippe orcel, dr pascal richette (paris - Lariboisière), pr pierre Lafforgue (Marseille), dr patrick Boumier (Amiens), pr Jean-Michel ristori, pr Martin Soubrier (Clermont-Ferrand), dr nadia Mehsen (Bordeaux), pr damien Loeuille (nancy), pr rené-Marc Flipo (Lille), pr Alain Saraux (Brest), pr Corinne Miceli (Le Kremlin Bicêtre), pr Alain Cantagrel (toulouse), pr olivier Vittecoq (rouen). the authors would also like to thank UrC-CIC paris Centre for the coordination and monitoring of the study. Contributors All authors contributed and finally approved the current manuscript. Competing interests none declared. Patient consent obtained. ethics approval Comitte de protection des personnes Ile de France III. Provenance and peer review not commissioned; externally peer reviewed. Open Access this is an open Access article distributed in accordance with the Creative Commons Attribution non Commercial (CC BY-nC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/ © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. no commercial use is permitted unless otherwise expressly granted. Publisher Copyright: © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved.Objective To estimate sacroiliac joint radiographic (X-SIJ) progression in patients with axial spondyloarthritis (axSpA) and to evaluate the effects of inflammation on MRI (MRI-SIJ) on X-SIJ progression. Methods X-SIJ and MRI-SIJ at baseline and after 2 and 5 years in patients with recent onset axSpA from the DESIR cohort were scored by three central readers. Progression was defined as (1) the shift from non-radiographic (nr) to radiographic (r) sacroiliitis (by modified New York (mNY) criteria) or alternative criteria, (2) a change of at least one grade or (3) a change of at least one grade but ignoring a change from grade 0 to 1. The effects of baseline inflammation on MRI-SIJ on 5-year X-SIJ damage (mNY) were tested by generalised estimating equations. Results In 416 patients with pairs of baseline and 5-year X-SIJ present, net progression occurred in 5.1% (1), 13.0% (2) and 10.3% (3) respectively, regarding a shift from nr-axSpA to r-axSpA (1), a change of at least one grade (2) or a change of at least one grade but ignoring a change from grade 0 to 1 (3). Baseline MRI-SIJ predicted structural damage after 5 years in human leukocyte antigen-B27 (HLA-B27) positive (OR 5.39 (95% CI 3.25 to 8.94)) and in HLA-B27 negative (OR 2.16 (95% CI 1.04 to 4.51)) patients. Conclusions Five-year progression of X-SIJ damage in patients with recent onset axSpA is limited but present beyond measurement error. Baseline MRI-SIJ inflammation drives 5-year radiographic changes.publishersversionpublishe

The revised Bristol Rheumatoid Arthritis Fatigue measures and the Rheumatoid Arthritis Impact of Disease scale: Validation in six countries

© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. Objective. To evaluate the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAFMDQ), the revised Bristol Rheumatoid Arthritis Numerical Rating Scales (BRAF-NRS V2) and the Rheumatoid Arthritis Impact of Disease (RAID) scale in six countries. Methods. We surveyed RA patients in France, Germany, The Netherlands, Spain, Sweden and the UK, including the HAQ, 36-item Short Form Health Survey (SF-36) and potential revisions of the BRAF-NRS coping and Spanish RAID coping items. Factor structure and internal consistency were examined by factor analysis and Cronbach's α and construct validity by Spearman's correlation. Results. A total of 1276 patients participated (76% female, 25% with a disease duration < 5 years, median HAQ 1.0). The original BRAF-MDQ four-factor structure and RAID single-factor structure were confirmed in every country with ≥66% of variation in items explained by each factor and all item factor loadings of 0.71-0.98. Internal consistency for the BRAF-MDQ total and subscales was a Cronbach's α of 0.75-0.96 and for RAID, 0.93-0.96. Fatigue construct validity was shown for the BRAF-MDQ and BRAF-NRS severity and effect scales, correlated internally with SF-36 vitality and with RAID fatigue (r = 0.63-0.93). Broader construct validity for the BRAFs and RAID was shown by correlation with each other, HAQ and SF-36 domains (r = 0.46-0.82), with similar patterns in individual countries. The revised BRAF-NRS V2 Coping item had stronger validity than the original in all analyses. The revised Spanish RAID coping item performed as well as the original. Conclusion. Across six European countries, the BRAF-MDQ identifies the same four aspects of fatigue, and along with the RAID, shows strong factor structure and internal consistency and moderate-good construct validity. The revised BRAF-NRS V2 shows improved construct validity and replaces the original

Association of Diverticulitis with Prolonged Spondyloarthritis: An Analysis of the ASAS-COMOSPA International Cohort

This study examined the relationship between spondyloarthritis (SpA) duration and gastrointestinal comorbidities other than inflammatory bowel disease (IBD). We evaluated the association between SpA duration and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis using data from a large international cross-sectional study. Binary regression models were created, adjusted for age, sex, body mass index (BMI), smoking, alcohol, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, IBD history and country. Subgroup analysis was performed by disease phenotype. The data of 3923 participants were analysed. The prevalence of gastrointestinal conditions were 10.7% upper gastrointestinal ulcers; 4.7% viral hepatitis and 1.5% diverticulitis. While SpA duration was not associated with upper gastrointestinal ulcers, HBV or HCV, longer SpA duration was significantly associated with diverticulitis (odds ratios (OR) = 1.18, 95% confidence interval (CI): 1.03–1.34), reflecting an 18% increase for every five years of SpA duration. Other significant associations with diverticulitis were age and high alcohol intake but not medication history. In subgroup analyses, the association was strongest with those with axial SpA. The reasons for this association of increased diverticulitis with disease duration in SpA, especially those with axial disease, are unclear but may reflect shared underlying gut inflammation. Diverticulitis should be considered, in addition to IBD, when SpA patients present with lower gastrointestinal symptoms