Sick leave in early axial spondyloarthritis: the role of clinical and socioeconomic factors. Five-year data from the DESIR cohort

Un nouvel article scientifique intitulé «Sick leave in early axial spondyloarthritis: the role of clinical and socioeconomic factors. Five-year data from the DESIR cohort» a été publié dans le journal RMD Open.

Nikiphorou E, Carvalho PD, Boonen A, Fautrel B, Richette P, Machado PM, van der Heijde D, Landewé R, Ramiro S.

Objectives:

To investigate the occurrence of sick leave (SL) and the impact of clinical and socioeconomic factors on SL in early axial spondyloarthritis (axSpA).

Methods:

Patients with a clinical diagnosis of axSpA from the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort with work-related data and up to 5-year follow-up were studied. Incidence, time to first SL and potential role of baseline and time-varying clinical and socioeconomic factors (age, gender, ethnicity, education, job type, marital and parental status) were analysed. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable time-varying Cox survival model building.

Results:

In total, 704 axSpA patients were included (mean (SD) age 33.8 (8.6); 46% men). At baseline, 80% of patients were employed; of these, 5.7% reported being on SL. The incidence of SL among those at risk during the study period (n=620, 88%) was 0.05 (95% CI 0.03 to 0.06) per 1000 days of follow-up. Mean (SD) time to first SL was 806 (595) days (range: 175-2021 days). In multivariable models, male gender (HR 0.41 (95% CI 0.20 to 0.86)) and higher education (HR 0.48 (95% CI 0.24 to 0.95)) were associated with lower hazard of SL, while higher disease activity (HR 1.49 (95% CI 1.04 to 2.13)), older age, smoking and use of tumour necrosis factor inhibitors were associated with higher hazard of SL.

Conclusions:

In this early axSpA cohort of young, working-age individuals, male gender and higher education were independently associated with a lower hazard of SL, whereas older age and higher disease activity were associated with higher hazard of SL. The findings suggest a role of socioeconomic factors in adverse work outcomes, alongside active disease.

Keywords: ankylosing; epidemiology; inflammation; spondylitis.

EULAR 2021

Lors du congrès de l’EULAR 2021 qui s’est déroulé du 2 au 5 juin 2021 en visioconférence, 6 abstracts ont été acceptés pour une présentation orale ou par poster :

Présentation orale

▫ FACTORS ASSOCIATED WITH REMISSION AT 5 YEARS OF FOLLOW-UP IN EARLY ONSET AXIAL SPONDYLOARTHRITIS: RESULTS FROM THE DESIR COHORT, L. Pina Vegas, E. Sbidian, D. Wendling, P. Goupille, S. Ferkal, P. Le Corvoisier, B. Ghaleh, A. Luciani, P. Claudepierre

▫ IMPACT OF CORRECTING CRP THRESHOLD ACCORDING TO BMI ON DIAGNOSIS, DISEASE ACTIVITY, INDICATION OF BIOLOGICAL TREATMENT AND PREDICTION OF THERAPEUTIC RESPONSE, IN PATIENTS SUSPECTED OF AXIAL SPONDYLOARTHRITIS. RESULTS FROM DESIR COHORT, O. Facorat, J. Morel, B. Combe, P. Richette, C. Lukas

Présentations par affiches.

▫ NO DIFFERENCE BETWEEN THE SEROLOGIES OF DENTAL GERMS AND THE PHENOTYPES OF SPONDYLOARTHRITIS WITHIN THE DESIR COHORT, T. Neel, A. Tournadre, M. Paul, M. Norman, S. Paul, H. Marotte

▫ HOW DO CLINICAL AND SOCIOECONOMIC FACTORS IMPACT ON WORK DISABILITY IN EARLY AXIAL SPONDYLOARTHRITIS? FIVE-YEAR DATA FROM THE DESIR COHORT, E. Nikiphorou, A. Boonen, B. Fautrel, P. Richette, R. B. M. Landewé, D. Van der Heijde, S. Ramiro

▫ SICK LEAVE AND ITS PREDICTORS IN EARLY AXIAL SPONDYLOARTHRITIS: THE ROLE OF CLINICAL AND SOCIOECONOMIC FACTORS. FIVE-YEAR DATA FROM THE DESIR COHORT, E. Nikiphorou, P. Carvalho, A. Boonen, B. Fautrel, P. Richette, P. M. Machado, D. Van der Heijde, R. B. M. Landewé, S. Ramiro

▫ WHAT IS THE DIAGNOSTIC VALUE OF IMPAIRED SPINAL MOBILITY MEASUREMENTS IN INFLAMMATORY BACK PAIN PATIENTS? DATA FROM THE DESIR COHORT, C. Lukas, G. Khoury, M. A. D’agostino, B. Combe, J. Morel

Development and validation of an alternative ankylosing spondylitis disease activity score when patient global assessment is unavailable

Un nouvel article scientifique intitulé «Development and validation of an alternative ankylosing spondylitis disease activity score when patient global assessment is unavailable» a été publié dans le journal Rheumatology (Oxford).

Ortolan A, Ramiro S, van Gaalen F, Kvien TK, Landewe RBM, Machado PM, Ruyssen-Witrand A, van Tubergen A, Bastiaenen C, van der Heijde D.

Objective:

To develop an alternative Ankylosing Spondylitis Disease Activity Score (ASDAS) to be used in research settings in axial SpA (axSpA) when Patient Global Assessment (PGA) is unavailable in databases.

Methods:

Longitudinal data from four axSpA cohorts and two randomized controlled trials were combined. Observations were randomly split in a development (N = 1026) and a validation cohort (N = 1059). Substitutes of PGA by BASDAI total score, single or combined individual BASDAI questions, and a constant value, were established in the development cohort. Conversion factors for each substitute were defined by Generalized Estimating Equations, obtaining seven ‘alternative’ formulae. Validation was performed in the validation cohort according to the OMERACT filter, taking into consideration: (i) truth (agreement with original-ASDAS in the continuous score, by intraclass correlation coefficient and in disease activity states, by weighted kappa); (ii) discrimination [standardized mean difference of ASDAS scores between high/low disease activity states defined by external anchors, e.g. Patient Acceptable Symptom State; agreement (kappa) in the percentage of patients reaching ASDAS improvement criteria according to alternative vs original formulae]; and (iii) feasibility.

Results:

Comparing various options, alternative-ASDAS using BASDAI total as PGA replacement proved to be: truthful (intraclass correlation coefficient = 0.98, kappa = 0.90), discriminative [ASDAS scores between Patient Acceptable Symptom State no/yes: standardized mean difference = 1.37 (original-ASDAS standardized mean difference = 1.43); agreement with original-ASDAS in major improvement/clinically important improvement criteria: kappa = 0.93/0.88] and feasible (BASDAI total often available, as questions required for the ASDAS; conversion coefficient ≈ 1).

Conclusion:

Alternative-ASDAS using BASDAI total score as PGA replacement is the most truthful, discriminative and feasible instrument.

Keywords: axial spondyloarthrits; disease activity; patient-reported outcomes; validation.

Structural changes in the sacroiliac joint on MRI and relationship to ASDAS inactive disease in axial spondyloarthritis: a 2-year study comparing treatment with etanercept in EMBARK to a contemporary control cohort in DESIR

Un nouvel article scientifique intitulé «Structural changes in the sacroiliac joint on MRI and relationship to ASDAS inactive disease in axial spondyloarthritis: a 2-year study comparing treatment with etanercept in EMBARK to a contemporary control cohort in DESIR» a été publié dans le journal Arthritis Res Ther.

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.

Background:

Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis (axSpA). We compared 2-year structural lesion changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) of patients with recent-onset axSpA receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). We also evaluated the relationship between the Ankylosing Spondylitis Disease Activity Score (ASDAS) and change in MRI structural parameters.

Methods:

The difference between etanercept (EMBARK) and control (DESIR) in the net percentage of patients with structural lesion change was determined using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score, with and without adjustment for baseline covariates. The relationship between sustained ASDAS inactive disease, defined as the presence of ASDAS < 1.3 for at least 2 consecutive time points 6 months apart, and structural lesion change was evaluated.

Results:

This study included 163 patients from the EMBARK trial and 76 from DESIR. The net percentage of patients with erosion decrease was significantly greater for etanercept vs control: unadjusted: 23.9% vs 5.3%; P = 0.01, adjusted: 23.1% vs 2.9%; P = 0.01. For the patients attaining sustained ASDAS inactive disease on etanercept, erosion decrease was evident in significantly more than erosion increase: 34/104 (32.7%) vs 5/104 (4.8%); P < 0.001. A higher proportion had erosion decrease and backfill increase than patients in other ASDAS status categories. However, the trend across ASDAS categories was not significant and decrease in erosion was observed even in patients without a sustained ASDAS response.

Conclusions:

These data show that a greater proportion of patients achieved regression of erosion with versus without etanercept. However, the link between achieving sustained ASDAS inactive disease and structural lesion change on MRI could not be clearly established.

Keywords: ASDAS; Anti-TNF; Axial spondyloarthritis; Etanercept; MRI; Sacroiliac joint.

Long-term association between disease activity and disability in early axial spondyloarthritis: results from the DESIR cohort

Un nouvel article scientifique intitulé «Long-term association between disease activity and disability in early axial spondyloarthritis: results from the DESIR cohort» a été publié dans le journal Arthritis Care Res (Hoboken).

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

Objectives:

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

Methods:

We analysed data collected during the first five years of follow-up of a large early axSpA cohort – the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. Multivariable models were built to study the association between Ankylosing Spondylitis Health Assessment Questionnaire (HAQ-AS) and Ankylosing Spondylitis Disease Activity Score 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 5152 visits were analysed. HAQ-AS was longitudinally, independently and positively associated with ASDAS-CRP [adjusted (adj) B=0.205, (95% confidence interval (CI)= 0.187 to 0.222], enthesitis score (adjB=0.011, CI=0.008 to 0.015), Bath Ankylosing Spondylitis Metrology Index (BASMI) (adjB=0.087, CI=0.069 to 0.105) and female gender (adjB=0.172, CI=0.120 to 0.225). The CHAID decision tree revealed ASDAS-CRP as the first variable with discriminative power on HAQ-AS. The cut-offs 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 axSpA. ASDAS-CRP cut-offs that separated different patient disability profiles largely mimicked the cut-offs previously defined for ASDAS-CRP disease activity states.

Uveitis occurrence in early inflammatory back pain. Five years data from the prospective French nationwide DESIR cohort

Un nouvel article scientifique intitulé «Uveitis occurrence in early inflammatory back pain. Five years data from the prospective French nationwide DESIR cohort» a été publié dans le journal Joint Bone Spine.

Daniel Wendling, Clément Prati, Thierry Lequerré, Corinne Miceli, Maxime Dougados, Anna Molto, Xavier Guillot.

Objective:

Uveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors.

Methods:

DESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed.

Significance: p less than 0.05.

Results:

After 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI : 15.4-22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84 - 1.74] / 100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI.

Conclusion:

Five-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.

Keywords:

Uveitis; cohort; dactylitis; spondyloarthritis.

Determining factors related to impaired spinal and hip mobility in patients with axial spondyloarthritis: longitudinal results from the DESIR cohort

Un nouvel article scientifique intitulé «Determining factors related to impaired spinal and hip mobility in patients with axial spondyloarthritis: longitudinal results from the DESIR cohort» a été publié dans le journal RMD Open.

Pedro D Carvalho, Adeline Ruyssen-Witrand, Joao Fonseca, Ana Marreiros, Pedro M Machado.

Objective:

To investigate the determinants of impaired spinal and hip mobility in patients with early axial spondyloarthritis (axSpA).

Methods:

Five-year longitudinal data from the DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR) cohort were analysed. Associations were investigated using generalised estimating equations, using Bath Ankylosing Spondylitis Metrology Index (BASMI) linear or each of the five components of BASMI as dependent variables, and clinical and demographic variables as independent variables in univariable models. Multivariable analyses were performed, adjusting for potential confounders.

Results:

Data from 644 patients and 5152 visits were analysed. Higher BASMI values were independently and positively associated with Ankylosing Spondylitis Disease Activity Score C reactive protein (ASDAS-CRP) (adjusted B (adjB)=0.21; 95% CI=0.15 to 0.28), MRI spinal inflammation score (adjB=0.11; 95% CI=0.04 to 0.19), enthesitis score (adjB=0.02; 95% CI=0.01 to 0.04) and age (adjB=0.02; 95% CI=0.01 to 0.03). All BASMI components were independently associated with ASDAS-CRP and MRI spinal inflammation, except for maximal intermalleolar distance (reflecting hip mobility), which was not associated with MRI spinal inflammation.

Conclusion:

In early axSpA, spinal mobility impairment is independently determined by clinical disease activity, MRI spinal inflammation, enthesitis and age. The influence of spinal inflammation prevails in early axSpA, as opposed to spinal structural damage, which may become more relevant in later disease stages.

Keywords:

Ankylosing; MRI; Patient Reported Outcome Measures; Spondylitis.

Determinants of the physician global assessment of disease activity and influence of contextual factors in early axial spondyloarthritis

Un nouvel article scientifique intitulé «Determinants of the physician global assessment of disease activity and influence of contextual factors in early axial spondyloarthritis» a été publié dans le journal Arthritis Care Res (Hoboken).

Fumio Hirano, Robert B M Landewé, Floris A van Gaalen, Désirée van der Heijde, Cécile Gaujoux-Viala, Sofia Ramiro.

Objectives:

To investigate determinants of the physician global assessment of disease activity (PhGA) and the influence of the contextual factors on this relationship in patients with early axial spondyloarthritis (axSpA).

Method:

Five-year data of DESIR, a cohort of early axSpA, were analyzed. Univariable generalized estimating equations (GEE) were used to investigate contributory explanatory effects of various potential determinants of PhGA. Effect modification by contextual factors (age, gender and educational level) was tested and, if significant, models were stratified. Autoregressive GEE models (i.e., models adjusted for PhGA at the previous time point) were used to confirm a longitudinal relationship.

Results:

A total of 708 patients were included. Higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) individual questions, swollen joint count in 28 joints (SJC28), tender joint count in 53 joints, Maastricht Ankylosing Spondylitis Enthesitis Score, C-reactive protein (CRP) and Bath Ankylosing Spondylitis Metrology Index were associated with a higher PhGA. Gender and age were effect modifiers of SJC28; the contributory effect of SJC28 was largest in the younger male stratum (β [95% CI]; 1.07 [0.71-1.43]), and the smallest in the older female stratum (0.13 [0.04-0.22]). Autoregressive GEE models revealed the same determinants as having a longitudinal association with PhGA and the same pattern of effect modification.

Conclusions:

Patient’s subjective symptoms, peripheral arthritis and enthesitis, higher CRP and impaired spinal mobility contribute to explaining PhGA in patients with early axSpA irrespective of gender and age. Intriguingly, physicians consider the presence of swollen joints as more important in males than in females.

Which imaging outcomes for axSpA are most sensitive to change? A 5-Year analysis of The DESIR Cohort

Un nouvel article scientifique intitulé «Which imaging outcomes for axSpA are most sensitive to change? A 5-Year analysis of The DESIR Cohort» a été publié dans le journal Arthritis Care Res (Hoboken).

Alexandre Sepriano, Sofia Ramiro, Désirée van der Heijde, Maxime Dougados, Pascal Claudepierre, Antoine Feydy, Monique Reijnierse, Damien Loeuille, Robert Landewé.

Objective:

To compare the sensitivity to change of different imaging scoring methods in patients with early axial spondyloarthritis (axSpA).

Methods:

Patients from the DESIR cohort fulfilling the ASAS axSpA criteria were included. Radiographs and MRI of the sacroiliac joints (SIJ) and spine were obtained at baseline, 1, 2 and 5 years. Each image was scored by 2 or 3 readers in 3 separate ‘reading-waves’. The rate of change of outcomes measuring spinal and SIJ inflammation (e.g. SPARCC score) and structural damage on MRI (e.g. ≥3 fatty lesions) and radiographs (e.g. mNY grading) was assessed using multilevel generalized estimating equations (GEE) models (taking all readers and waves into account). To allow comparisons across outcomes, rates were standardized (difference between the individual’s value and the population mean divided by the standard deviation).

Results:

In total, 345 patients were included. Inflammation on MRI-SIJ (standardized rate range: -0.278; -0.441) was more sensitive to change compared to spinal inflammation (range: -0.030; -0.055). Structural damage in the SIJ showed a higher standardized rate of change on MRI-SIJ (range: 0.015-0.274) compared to X-SIJ (range: 0.043-0.126). MRI-SIJ damage defined by ≥3 fatty lesions showed the highest sensitivity to change (0.274). Spinal structural damage slowly progressed over time with no meaningful difference between radiographic (range: 0.037-0.043) and MRI structural outcomes (range: 0.008-0.027).

Conclusion:

Structural damage assessed in pelvic radiographs has low sensitivity to change, while fatty lesions detected on MRI-SIJ are a promising alternative. In contrast, MRI-spine is not better than X-spine in detecting structural changes in early axSpA patients.

Keywords: Axial spondyloarthritis; imaging; sensitivity to change.

Inflammation of the sacroiliac joints and spine on MRI predicts structural changes on MRI in axial spondyloarthritis: 5-year data from DESIR

Un nouvel article scientifique intitulé «Inflammation of the sacroiliac joints and spine on MRI predicts structural changes on MRI in axial spondyloarthritis: 5-year data from DESIR » a été publié dans le journal Arthritis Care Res (Hoboken).

Alexandre Sepriano, Sofia Ramiro, Robert Landewé, Anna Moltó, Pascal Claudepierre, Daniel Wendling, Maxime Dougados, Désirée van der Heijde.

Objective:

To test the impact of inflammation on MRI-structural changes occurring in the sacroiliac joints (SIJ) and the spine.

Methods:

Patients with early axSpA from the DESIR cohort were included. MRIs of the SIJ (MRI-SIJ) and spine (MRI-spine), obtained at baseline, 2 and 5 years, were scored by 3 central readers. Inflammation and structural damage on MRI-SIJ/MRI-spine were defined by the agreement of ≥2 of 3 readers (binary outcomes), and by the average of 3 readers (continuous outcomes). The effect of inflammation (MRI-SIJ/MRI-spine) on damage (MRI-SIJ/MRI-spine, respectively) was evaluated in two models: i. Baseline prediction model: effect of baseline inflammation on damage assessed at 5-year; and ii. Longitudinal model: effect of inflammation on structural damage assessed during 5 years.

Results:

202 patients were included. Both the presence of bone marrow edema (BME) on MRI-SIJ and on MRI-spine at baseline were predictive of 5-year damage (≥3 fatty lesions) on MRI-SIJ [OR=4.2 (95% CI: 2.4; 7.3)] and MRI-spine [OR=10.7 (95% CI: 2.4; 49.0)], respectively, when adjusted for CRP. The association was also confirmed in longitudinal models (when adjusted for ASDAS) both in the SIJ [OR=5.1 (95% CI: 2.7; 9.6)] and spine [OR=15.6 (95% CI: 4.8; 50.3)]. Analysis of other structural outcomes (i.e. erosions) on MRI-SIJ yielded similar results. In the spine, a significant association was found for fatty lesions but not for erosions and bone spurs, which occurred infrequently over time.

Conclusion:

We found a predictive and longitudinal association between MRI-inflammation and several types of MRI-structural damage in patients with early axSpA which adds to the proof for a causal relationship.

Keywords:

Axial spondyloarthritis; Inflammation; magnetic resonance imaging; structural damage.