Sensitivity to change of structural outcomes in axial spondyloarthritis after 10 years of follow up. Data from the DESIR cohort

Un nouvel article scientifique intitulé «Sensitivity to change of structural outcomes in axial spondyloarthritis after 10 years of follow up. Data from the DESIR cohort» a été publié dans le journal RMD Open. López-Medina C, Molto A, Sepriano A, Ramiro S, Tournadre A, Dougados M.

Objective:

To evaluate the sensitivity to change in structural imaging outcomes over 10 years of follow-up in patients with axial spondyloarthritis (axSpA).

Methods:

Patients with axSpA from the Devenir des Spondyloarthropathies Indifferénciées Récentes cohort were included. Radiographs and MRIs of the sacroiliac joints (SIJ) and spine were obtained at baseline and at 1, 2, 5 and 10 years. The yearly rate of change of each structural outcome was analysed using generalised estimating equation models, including all patients with ≥1 score from ≥1 reader from ≥1 reading wave, using the time (years) as an explanatory variable and adjusting for reader and wave. All outcomes were standardised, and the relative standardised rate of change was calculated (ie, the standardised rate of an outcome divided by the rate of a reference outcome).

Results:

A total of 659 patients (46% males and mean age 33.6 years) were included. The most sensitive outcome to change in the SIJ (both MRI and radiographs) was the presence of ≥3 fatty lesions at a specific timepoint, with a relative standardised rate of change per year of 5.28 using the modified New York criteria as reference.Similarly, the most sensitive to change (in both MRI and radiographs) outcome in the spine was the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; relative standardised yearly change 1.76) using ≥1 syndesmophyte as reference.

Conclusion:

MRI structural outcomes in the SIJ (ie, fatty lesions) are more sensitive to change than radiographic outcomes. Conversely, the mSASSS remains the most sensitive method, even when compared with MRI of the spine.

Diagnosis challenges in inception cohorts in axial spondyloarthritis: the case of the French national DESIR cohort

Un nouvel article scientifique intitulé «Diagnosis challenges in inception cohorts in axial spondyloarthritis: the case of the French national DESIR cohort» a été publié dans le journal RMD Open. Molto A, Serrand C, Alonso S, Berenbaum F, Claudepierre P, Combe B, Gossec L, Ruyssen-Witrand A, Saraux A, Wendling D, Lequerre T, Dougados M.

Background:

Inception cohorts aim to describe chronic diseases from diagnosis and over years of follow-up. Axial spondyloarthritis (axSpA) diagnosis might be challenging during the first years of the disease. Thus, identifying the features that will be associated with a confirmed diagnosis over time is key.

Objectives:

To assess the frequency and the predisposing factors for a change of an initial diagnosis in an inception axSpA cohort.

Methods:

DESIR is an ongoing national multicentre inception axSpA cohort with currently 12.5 years of follow-up. At the entry visit and confirmed at each visit, the diagnosis of axSpA was based on the opinion of the treating rheumatologist. Follow-up was interrupted in case of a change in this initial diagnosis. Multiple imputation was used to estimate the probability of a change in the initial diagnosis of axSpA for each patient lost to follow-up. Factors predisposing to an unchanged diagnosis of axSpA were then assessed using a multivariate logistic regression model on the imputed data sets.

Results:

Of the 708 patients included, over 10 years of follow-up, 45 (6.4%) were excluded due to a diagnosis change and 300 (42.4%) patients were lost to follow-up. Based on the imputation of these 300 patients, a change in their initial axSpA diagnosis was estimated in 42 (14.0%). Factors predisposing to an unchanged initial axSpA diagnosis during follow-up were (ORs (95% CIs)): radiographic sacroiliitis: 17.0 (4.1 to 71.0); psoriasis: 5.3 (2.0 to 14.3); CRP≥6 mg/L: 2.7 (1.3 to 5.3); good NSAID response: 2.5 (1.5 to 4.2); HLA B27+: 2.0 (1.3 to 3.3); anterior chest wall pain: 2.0 (1.2 to 3.3) and female sex: 1.9 (1.2 to 3.0).

Conclusion:

These data suggest that a change in diagnosis in recent onset axSpA exists, but is not frequent, and is less likely to occur in the presence of objective features at baseline.

Impact of pregnancy on sacroiliac imaging in women with axial spondyloarthritis: results of the analysis of the DESIR cohort

Un nouvel article scientifique intitulé «Impact of pregnancy on sacroiliac imaging in women with axial spondyloarthritis: results of the analysis of the DESIR cohort» a été publié dans le journal Scand J Rheumatol. Portier E, Dougados M, Ruyssen-Witrand A, Moltó A.

Objective:

In postpartum healthy women, inflammatory lesions of the sacroiliac joint (SIJ) can appear and mimic sacroiliitis. However, the impact of delivery on imaging abnormalities in women with axial spondyloarthritis (axSpA) is unknown. Thus, this study aimed to evaluate the impact of delivery on SIJ imaging in early axSpA.

Method:

Women with axSpA from the French prospective cohort DESIR were included, with a follow-up of 5 years. Demographic and disease characteristics, and SIJ imaging abnormalities at baseline, were described in all women and then according to nulliparous status. Changes on imaging over time were analysed in the 38 women who were nulliparous at baseline and had their first pregnancy with delivery during follow-up.

Results:

At baseline, nulliparous women were younger and had a higher educational level than other women with axSpA. The presence of sacroiliitis on magnetic resonance imaging (MRI) and X-ray was more frequent in nulliparous women (16.9% vs 9.9% and 33.8% vs 19.4%, respectively). When focusing on first incident deliveries, these patients had more sacroiliitis on X-ray and MRI at baseline than nulliparous patients at the end of follow-up, but lower Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP). Only the modified New York score on the left SIJ was statistically different after delivery.

Conclusion:

Pregnancy with delivery does not seem to aggravate imaging in women with. Following axSpA patients who had their first delivery showed a mild increase in left sacroiliitis on X-ray after delivery, but without other signs of structural or inflammatory aggravation on imaging.

Clinical and imaging outcomes of different phenotypes of axial spondyloarthritis: 5-year analysis of the DESIR cohort

Un nouvel article scientifique intitulé «Clinical and imaging outcomes of different phenotypes of axial spondyloarthritis: 5-year analysis of the DESIR cohort» a été publié dans le journal Semin Arthritis Rheum. Sepriano A, Ramiro S, van der Heijde D, Moltó A, Gaujoux-Viala C, Dougados M, Landewé R.

Objectives:

To compare the long-term outcomes of three phenotypes of axial SpA (axSpA).

Methods:

Patients with a clinical diagnosis of axSpA from the DESIR cohort were grouped into three phenotypes at baseline: ‘Pure axSpA’ (’Axial’), ‘axSpA with peripheral signs’ (’IBP+Peripheral’) and ‘axSpA at risk’ (’At risk’) by latent class analysis. Clinical and imaging data were collected up to 5 years. Clinical outcomes, measured in each visit, included disability (BASFI) and quality of life (QoL; SF36). Imaging outcomes included inflammatory and structural lesions on MRI and radiographs of spine and SIJ. The association between phenotype membership at baseline and each outcome was tested in multivariable GEE models.

Results:

In total, 576 patients with axSpA were included. ‘At risk’ patients had worse disability and QoL than ‘Axial’ patients over time. For instance, ‘At risk’ patients had on average 0.4 more points in BASFI over time than ‘Axial’ patients [β (95 % CI): 0.4 (0.2; 0.7)]. This difference was mostly noted in female patients who were HLA-B27 positive. In addition, the difference between the ‘At risk’ and ‘Axial’ phenotypes was higher in patients receiving bDMARDs than in those not (β=0.6 vs 0.5), since BASFI improved more in ‘Axial’ (∆BASFI: -1.3) than in ‘At risk’ (∆BASFI: -0.9) treated patients. There were no differences in disability and QoL between ‘Axial’ and ‘IBP+Peripheral’ patients. Imaging outcomes were worse in the ‘Axial’ phenotype than in the others over time.

Conclusion:

Patients with ‘axSpA at risk’ show worse self-reported outcomes over time and are less likely to benefit from anti-inflammatory treatment than those with a classical axSpA phenotype.

Erosions on T1-Weighted Magnetic Resonance Imaging Versus Radiography of Sacroiliac Joints in Recent-Onset Axial Spondyloarthritis: 2-Year Data (EMBARK Trial and DESIR Cohort)

Un nouvel article scientifique intitulé «Erosions on T1-Weighted Magnetic Resonance Imaging Versus Radiography of Sacroiliac Joints in Recent-Onset Axial Spondyloarthritis: 2-Year Data (EMBARK Trial and DESIR Cohort)» a été publié dans le journal J Rheumatol. Maksymowych WP, Claudepierre P, de Hooge M, Lambert RG, Landewé R, Molto A, van der Heijde D, Bukowski JF, Jones H, Pedersen R, Szumski A, Vlahos B, Dougados M.

Objective: (1)

To compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-week 104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); and (2) to compare treatment-discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the Effect of Etanercept on Symptoms and Objective Inflammation in Nonradiographic axSpA (EMBARK) trial vs controls in the DESIR (Devenir des Spondylarthropathies Indifférenciées Récentes) cohort.

Methods:

Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥ 2 of 3 readers’ assessments.

Results:

At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P < 0.001). After 104 weeks, a decrease in erosions was observed on MRI but not radiographs in 49/221 (22.2%) patients, and on radiographs but not MRI in 6/221 (2.7%) patients (P < 0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, changes in erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedges G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively.

Conclusion:

In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research. [ClinicalTrials.gov: NCT01258738NCT01648907].

DESIR SNIIRAM – Lettre non opposition pour les patients

Paris, le 30/11/2023

Objet : Projet de recherche grâce à l’utilisation des données collectées par votre caisse d’assurance maladie

Madame, Monsieur,

Grâce à votre participation à cette cohorte, de nombreuses recherches ont pu être menées et ainsi permettre une amélioration de nos connaissances de l’évolution de la spondyloarthrite. Nous voulons aller plus loin en nous aidant non seulement des informations recueillies lors de chacune de vos  visites dans le centre mais également grâce aux données recueillies en routine par votre Caisse Nationale de l’Assurance Maladie (CNAM),  issues des demandes de remboursement de soins et prestations.

Pour cela, nous vous avions contacté en 2018 pour vous informer de notre projet.  A cette époque, nous avons demandé à la CNAM de rechercher les données vous concernant uniquement en leur fournissant certaines informations que l’on appelle non identifiantes (par exemple votre mois de naissance ou des dates de réalisation de soins que nous avions recueillies dans DESIR). Il s’est avéré  difficile de récupérer de cette façon vos données avec un niveau de certitude suffisant.

Récemment, la législation a évolué et permet à présent à des chercheurs d’avoir accès aux données de la caisse d’assurance maladie après avoir identifié les malades de manière certaine grâce à leur numéro de sécurité sociale.

Pour effectuer ces recherches, nous voudrions demander au centre qui vous prend en charge dans la cohorte DESIR de transmettre de façon sécurisée votre N° de sécurité sociale à la CNAM.

Le circuit prévu fait que ce N° de sécurité sociale ne sera jamais accessible aux chercheurs qui sont en charge de l’analyse des données. Vos données restent strictement confidentielles.

Le responsable du traitement de vos données est la Direction de la Recherche Clinique et de l’Innovation (DRCI) de l’Assistance Publique Hôpitaux de Paris (AP-HP). Le destinataire des données est l’AP-HP.

Tout traitement de données vous concernant sera effectué de manière confidentielle et sécurisée ;  en conformité avec la réglementation en vigueur, et avec l’autorisation préalable de la Commission Nationale de l’Informatique et des Libertés (CNIL).

Bien entendu, votre participation à ce volet de l’étude est facultative. A tout moment, vous pouvez refuser que nous utilisions vos données identifiantes pour la consultation des données de l’Assurance Maladie. Ce volet de l’étude commencera dans 1 mois.

Vous pouvez exercer vos droits d’opposition, d’effacement, de limitation et de rectification concernant les données de la cohorte DESIR par l’envoi d’un courrier postal (à Cohorte DESIR_ Centre de coordination _CHU Cochin, service de rhumatologie, 27 boulevard du faubourg St Jacques 75014 Paris) sans aucune répercussion sur votre prise en charge, la qualité des soins qui vous sont prodigués ou votre participation à la Cohorte DESIR. Si vous souhaitez avoir davantage d’informations sur cette initiative, n’hésitez pas à en parler à l’équipe soignante qui vous prend en charge dans le cadre de la cohorte DESIR.

Bien cordialement,

Pr Maxime DOUGADOS au nom du comité de coordination et du comité scientifique de la cohorte DESIR

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

Un nouvel article scientifique intitulé «Factors Associated With Treatment Pathways in Early Axial Spondyloarthritis: A Multistate Analysis of the 10-Year Follow-Up of the DESIR Cohort» a été publié dans le journal J Rheumatol. Portier E, Chevret S, Walter-Petrich A, Ruyssen-Witrand A, Dougados M, Moltó A.

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 (Devenir des Spondylarthropathies Indifférenciées Récentes), with a scheduled 10-year follow-up. A multistate model with 4 ordered treatment states (no treatment, nonsteroidal antiinflammatory drugs [NSAIDs], conventional synthetic disease-modifying antirheumatic drugs [csDMARDs], and tumor necrosis factor inhibitors [TNFi]) was defined, with 6 possible transitions. Restricted mean sojourn times in each state were estimated. Then, predictors of those transitions were assessed by multivariable Cox models.

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.

Sacroiliac radiographic progression over 10 years in axSpA: data from the DESIR inception cohort

Un nouvel article scientifique intitulé «Sacroiliac radiographic progression over 10 years in axSpA: data from the DESIR inception cohort» a été publié dans le journal Ann Rheum Dis. Molto A, López-Medina C, Sepriano A, Ramiro S, de Hooge M, van Lunteren M, Navarro-Compán V, Wendling D, Dougados M.

Objectives:

To evaluate sacroiliac radiographic progression over a 10-year follow-up and determine the baseline factors associated with such progression in patients with recent-onset axial spondyloarthritis (axSpA, <3 years).

Methods:

This analysis was performed in the DESIR cohort (NCT01648907). The radiographic status of the patients (radiographic axSpA (r-axSpA) vs non-radiographic axSpA (nr-axSpA)) was based on the modified New York (mNY) criteria. Information on mNY criteria on the pelvic radiographs was obtained in four reading waves over a 10-year period. Images were blinded and centrally read by 3 trained readers. The % of mNY net progressors (ie, number of ‘progressors’ minus number of ‘regressors’ divided by the total number of patients) was assessed in completers (ie, pelvic radiographs at baseline and 10 years). The yearly likelihood of mNY+ was estimated using an integrated analysis (ie, including all patients with at least one available mNY score (’intention-to-follow’ population) using a generalised estimating equations model and time-varying tumour necrosis factor (TNF) use as a confounder. Baseline predictors of mNY+ during 10 years were evaluated.

Results:

Completers included 294 patients, while intention-to-follow included 659 participants. In the completers, the net % progression (from nr-axSpA to r-axSpA) was 5.8%. In the intention-to-follow population, the probability of being mNY+ was estimated to increase 0.87% (95% CI 0.56 to 1.19) per year (ie, 8.7% after 10 years) while when introducing TNF inhibitors (TNFi) as a time-varying covariate, the probability was 0.45% (95% CI 0.09 to 0.81) (ie, 4.5% after 10 years). Baseline bone marrow oedema (BME) on MRI of the sacroiliac joints (SIJ) was associated with being mNY+ over time OR 6.2 (95% CI 5.3 to 7.2) and OR 3.1 (95% CI 2.4 to 3.9) in HLA-B27+ and HLA-B27-, respectively). Male sex, symptom duration >1.5 years, Axial Spondyloarthritis Disease Activity Score ≥2.1 and smoking (only in HLA-B27 positives) were also associated with being mNY+ over 10 years. BME was not found to be a mediator of the HLA-B27 effect on mNY+ at 10 years.

Conclusions:

The yearly likelihood of switching from nr-axSpA to r-axSpA in patients after 10 years of follow-up was low, and even lower when considering TNFi use.

Ten-Year Clinical Outcome of recent-onset Axial Spondyloarthritis: results from the DESIR inception Cohort

Un nouvel article scientifique intitulé «Ten-Year Clinical Outcome of recent-onset Axial Spondyloarthritis: results from the DESIR inception Cohort» a été publié dans le journal Joint Bone Spine.

Dougados M, Serrand C, Alonso S, Berenbaum F, Claudepierre P, Combe B, Gossec L, Witrand AR, Saraux A, Wendling D, Querré TL, Molto A.

Objectives:

This study aimed to evaluate the 10-year clinical outcome of patients with recent-onset axial spondyloarthritis (axSpA).

Methods:

Study design: The DESIR cohort is an inception cohort of axSpA patients.

Diagnosis and management:

The diagnosis and management of patients were based on the decision of the treating rheumatologist.

Statistical analysis:

Both complete cases and imputed data analyses were conducted.

Results:

Of the 708 enrolled patients, 45 were excluded due to a change in the baseline diagnosis, 3 patients died, and 300 were lost to follow-up over the 10y. In the completer population, one patient required bilateral total hip replacement, and 56 patients received a pension due to invalidity. The prevalence of main extra-musculoskeletal features increased from baseline to year 10: psoriasis from 18% to 30%, acute anterior uveitis from 10% to 18%, and inflammatory bowel disease from 5% to 10%. The most frequent comorbidity was hypertension, with an increase from 5% to 15% from baseline to year 10. In the imputed data analysis the estimated proportions of patients with an acceptable status at year 10 were 70% [95% CI: 63; 77] for acceptable PASS, 43% [95% CI: 37; 49] for BASDAI < 3, and 48% [95% CI: 41; 56] for ASDAS < 2.1.

Conclusion:

These findings suggest that despite a quite favorable 10-year outcome exists for severe outcomes, a large proportion of patients present with an important disease burden reflected by patient-reported outcomes. This information can be valuable for providing patients with information at the time of diagnosis.

Keywords: cohort; long-term prognosis; spondyloarthritis.

Impact of disease outcomes on the Assessment of SpondyloArthritis International Society Health Index (ASAS HI): a Bayesian network analysis of the DESIR cohort

Un nouvel article scientifique intitulé «Impact of disease outcomes on the Assessment of SpondyloArthritis International Society Health Index (ASAS HI): a Bayesian network analysis of the DESIR cohort» a été publié dans le journal RMD Open.

Redeker I, Landewé R, van der Heijde D, Ramiro S, Boonen A, Dougados M, Braun J, Kiltz U.

Objective:

The objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) in patients with axial spondyloarthritis (axSpA).

Methods:

Cross-sectional data collected at month 72 of the Devenir des Spondylarthropathies Indifferénciées Récentes cohort was analysed. Combining prior knowledge and observed data, probabilistic Bayesian network modelling was used to study how the interplay of different disease outcomes affects the ASAS HI, which measures disease-specific overall functioning and health. Disease outcomes comprised, among others, the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) and the Bath AS Functional Index (BASFI).

Results:

Data of 384 patients were analysed. The obtained structure suggests that ASAS HI is determined by both patient-reported physical function (BASFI) and disease activity (ASDAS). The parameters of the structural model show that an increase of ASDAS or BASFI by 1 unit corresponds to an increase of ASAS HI by 0.70 or 1.25 units, respectively. Moreover, the model suggests that disease activity has an indirect impact on ASAS HI via BASFI. No relationship between spinal mobility or structural damage and ASAS HI was found.

Conclusions:

This is the first structural model developed to better understand the construct and the interplay between clinically relevant outcomes related to ASAS HI in axSpA patients. It shows that disease activity and physical function have a strong impact on ASAS HI, confirming it to be a valid construct of overall functioning and health in axSpA patients.

Keywords: Epidemiology; Patient Reported Outcome Measures; Spondylitis, Ankylosing.