Evaluation of long-term TNFi effectiveness after a first switch in early axial spondyloarthritis considering time-varying prescription bias: an inverse-probability weighting analysis of the DESIR cohort

Un nouvel article scientifique intitulé «Evaluation of long-term TNFi effectiveness after a first switch in early axial spondyloarthritis considering time-varying prescription bias: an inverse-probability weighting analysis of the DESIR cohort» a été publié dans le journal RMD Open.

Marion Pons, Sylvie Chevret, Karine Briot, Maria-Antonietta d’Agostino, Christian Roux, Maxime Dougados, Anna Molto.

Objective:

To evaluate long-term effectiveness of tumour necrosis factor inhibitor (TNFi) after a first switch, and their associated factors in an early axial spondyloarthritis (axSpA) population, considering time-varying prescription bias.

Methods:

Observational prospective cohort (DEvenir des Spondylarthropathies Indifférenciées Récentes) with 5 years of follow-up, including 708 TNFi-naïve patients with early axSpA. Long-term effectiveness of TNFi after a first switch (ASAS40 response after at least 2 visits under treatment) were estimated using marginal structural models (implementing inverse-probability weighting and iterative propensity scores). Factors associated with the outcome were explored by multivariate Cox regression models.

Results:

The hazard to present an ASAS40 response after a first TNFi switch was increased (HR=2.4 (95% CI 1.9 to 3.0)); this response ratio was slightly lower compared with the response in TNFi naïve patients after a first TNFi (HR=3.3 (95% CI 2.9 to 3.8)). HLA-B27 positive was the only factor independently associated with ASAS40 response after a first TNFi switch.

Conclusion:

After application of innovative methods to overcome time-varying prescription bias, the magnitude of the TNFi response after a first switch was found to be numerically lower but clinically relevant from the response in TNFi-naïve patients.

Keywords: ankylosing; epidemiology; spondylitis; tumour necrosis factor inhibitors.

Prevalence and consequences of psoriasis in recent axial spondyloarthritis: an analysis of the DESIR cohort over 6 years

Un nouvel article scientifique intitulé «Prevalence and consequences of psoriasis in recent axial spondyloarthritis: an analysis of the DESIR cohort over 6 years» a été publié dans le journal RMD Open.

Florian Lucasson, Pascal Richette, Krystel Aouad, Adeline Ryussen-Witrand, Daniel Wendling, Bruno Fautrel, Laure Gossec.

Objectives:

The consequences of psoriasis associated to axial spondyloarthritis (axSpA) are unclear. The objectives were to determine the prevalence and the consequences of psoriasis in recent axSpA over 6 years of follow-up.

Methods:

The multicentric prospective cohort DESIR (NCT01648907) of adult patients with recent inflammatory back pain suggestive of axSpA was analysed over 6 years. Psoriasis was recorded at each visit and cumulative prevalence and incidence were calculated. Patients with vs without psoriasis at any time point were compared. Outcomes included disease activity (Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP), joint and enthesitis count, CRP), patient-reported outcomes for function (Health Assessment Questionnaire for axSpA, HAQ-AS) and quality of life, and treatment use over 6 years. Outcomes were compared through univariable and multivariable analyses, as well as linear mixed effect models.

Results:

In 589 patients, mean age 40.5±8.7 years, 45.8% men and baseline mean symptom duration 1.5±0.9 years, the cumulative prevalence of psoriasis increased from 16.8% (99/589) at baseline to 26.8% (158/589) at 6 years, leading to an incidence of 2.1/100 patient-years. Over 6 years of follow-up, patients with psoriasis developed more synovitis (p=0.008), and received more methotrexate (cumulative use, 25.5% vs 11.8%, p<0.001) and biological disease-modifying drugs (55.7% vs 38.5%, p<0.001). There were no significant consequences of psoriasis on other outcomes, including disease activity (ASDAS-CRP), functional capacity (HAQ-AS) and quality of life.

Conclusion:

Psoriasis is frequent in early axSpA. AxSpA patients with psoriasis had more swollen joints over time and received more biologics; they did not have worse outcomes related to axSpA in terms of activity and severity.

Keywords: ankylosing; biological therapy; patient reported outcome measures; spondylitis.

Cluster analysis in early axial spondyloarthritis predicts poor outcome in the presence of peripheral articular manifestations

Un nouvel article scientifique intitulé «Cluster analysis in early axial spondyloarthritis predicts poor outcome in the presence of peripheral articular manifestations» a été publié dans le journal Rheumatology (Oxford).

Costantino F, Aegerter P, Schett G, De Craemer AS, Molto A, Van den Bosch F, Elewaut D, Breban M, D’Agostino MA.

Objectives:

To assess whether two cluster analysis-based axial SpA (axSpA) endotypes (A for purely axial; B for both axial and peripheral) are stable over time and are associated with different long-term disease outcomes.

Methods:

K-means cluster analysis was performed at each visit (until 5 years) on 584 patients from the DESIR cohort, who completed all planned visits, and validated in 232 consecutive axSpA patients from the BeGiant cohort. Cluster stability overtime was assessed by kappa statistics. A generalized linear mixed-effect analysis was applied to compare outcomes between clusters. Classification and regression tree (CART) analysis was performed to determine a decision rule able to assign a given patient to a definite cluster at onset.

Results:

Both endotypes remained remarkably stable over time. In the DESIR cohort, patients in cluster B showed higher disease activity, worse functional outcome and higher need for anti-rheumatic drugs than patients in cluster A. CART analysis yielded three main clinical features (arthritis, enthesitis, and dactylitis) that accurately determined cluster assignment. These results could be replicated in the Be-GIANT cohort.

Conclusion:

Cluster-based axSpA endotypes were reproducible in two different cohorts, stable over time and associated with different long-term outcome. The axSpA endotype with additional peripheral disease manifestations is associated with more severe disease and requires more intensive drug therapy.

Keywords: cluster analysis; disease endotypes; outcome; progression; spondyloarthritis.

DESIR 10-20 ans : Newsletter Patient N°2

Bonjour,
Nous mettons en ligne aujourd’hui la nouvelle Newsletter patients rédigée par le Pr Laure GOSSEC, rhumatologue à l’hôpital La pitié-Salpêtrière.
Pour y avoir accès, merci de cliquer ici.

ACR 2021

Lors du congrès de l’ACR 2021 qui s’est déroulé du 5 au 9 novembre 2021 en visioconférence, 3 abstracts ont été acceptés :

▫ Sick Leave and Its Predictors in Early Axial Spondyloarthritis: The Role of Clinical and Socioeconomic Factors. Five-year Data from the DESIR Cohort, Elena Nikiphorou, Annelies Boonen, PEDRO CARVALHO, Bruno Fautrel, Pascal Richette, Pedro Machado, Désirée van der Heijde, Robert Landewé and Sofia Ramiro

▫ How Do Clinical and Socioeconomic Factors Impact on Work Disability in Early Axial Spondyloarthritis? Elena Nikiphorou, Annelies Boonen, Bruno Fautrel, Pascal Richette, Robert Landewé, Désirée van der Heijde and Sofia Ramiro

▫ De Novo Psoriasis Can Be Reported at Any Timepoint in Early Axial Spondyloarthritis: An Analysis of 6 Years of Follow-up of the DESIR Cohort, Florian LUCASSON, Pascal Richette, krystel aouad, Adeline RUYSSEN-WITRAND, Daniel Wendling, Bruno Fautrel and Laure Gossec

Fat mass and response to TNFα blockers in early axial spondyloarthritis: an analysis of the DESIR cohort

Un nouvel article scientifique intitulé «Fat mass and response to TNFα blockers in early axial spondyloarthritis: an analysis of the DESIR cohort» a été publié dans le journal Ann Rheum Dis.

Molto A, Tang S, Combe B, Dougados M, Richette P.

No abstract available

Keywords: ankylosing; cardiovascular diseases; spondylitis; therapeutics.

How do clinical and socioeconomic factors impact on work disability in early axial spondyloarthritis? Five-year data from the DESIR cohort

Un nouvel article scientifique intitulé «How do clinical and socioeconomic factors impact on work disability in early axial spondyloarthritis? Five-year data from the DESIR cohort» a été publié dans le journal Rheumatology (Oxford).

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

Objectives:

To investigate the impact of clinical and socioeconomic factors on work disability (WD) in early axial spondyloarthritis (axSpA).

Methods:

Patients from the DESIR cohort with a clinical diagnosis of axSpA were studied over 5 years. Time to WD and potential baseline and time-varying predictors were explored, with a focus on socioeconomic (including ethnicity, education, job-type, marital/parental status) and clinical (including disease activity, function, mobility) factors. Univariable analyses, collinearity, and interaction tests guided subsequent multivariable time-varying Cox survival analyses.

Results:

From 704 patients eligible for this study, the estimated incidence of WD amongst those identified at-risk (n = 663, 94%) and across the five-years of DESIR, was 0.05 (95% CI 0.03-0.06) per 1000 person-days. Significant differences in baseline socioeconomic factors, including lower educational status and clinical measures, including worse disease activity, were seen in patients developing WD over follow-up, compared with those who never did. In the main multivariable model, educational status was no longer predictive of WD, whereas the Ankylosing Spondylitis (AS) disease activity score (ASDAS) and the Bath AS functional index (BASFI) were significantly and independently associated with a higher hazard of WD (HR[95%CI] 1.79[1.27-2.54] and 1.42[1.22-1.65], respectively).

Conclusion:

WD was an infrequent event in this early axSpA cohort. Nevertheless, clinical factors were amongst the strongest predictors of WD, over socioeconomic factors, with worse disease activity and function independently associated with a higher hazard of WD. Disease severity remains a strong predictor of adverse work outcome even in early disease, despite substantial advances in therapeutic strategies in axSpA.

Keywords: adverse work outcomes; axSpA; disease activity; socioeconomic factors; work disability.

Factors associated with remission at 5-year follow-up in recent onset axial spondyloarthritis: results from the DESIR cohort

Un nouvel article scientifique intitulé «Factors associated with remission at 5-year follow-up in recent onset axial spondyloarthritis: results from the DESIR cohort» a été publié dans le journal Rheumatology (Oxford).

Pina Vegas L, Sbidian E, Wendling D, Goupille P, Ferkal S, Le Corvoisier P, Ghaleh B, Luciani A, Claudepierre P.

Objective:

The factors contributing to long-term remission in axial spondyloarthritis (axSpA) are unclear. We aimed to characterize individuals with axSpA at 5-year follow-up to identify baseline factors associated with remission.

Methods:

We included all patients from the DESIR cohort (recent onset axSpA) with available Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP<1.3) were compared to those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on tumor necrosis factor inhibitor (TNFi) exposure was used.

Results:

Overall, 111/449 (25%) patients were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared to 17% (34/202) of those exposed to TNFi. Patients in remission after 5-years were more likely to be male, HLA-B27+, have a lower body mass index (BMI), and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi, included lower BASDAI (adjusted odds ratio [ORa] 0.9, 95% confidence interval [95%CI] 0.8-0.9) and history of peripheral arthritis (ORa 2.1, 95%CI 1.2-5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95%CI 1.6-5.1), lower enthesitis index (ORa 0.8, 95%CI 0.7-0.9), lower BASDAI (ORa 0.9, 95%CI 0.9-0.9), and lower BMI (ORa 0.8, 95%CI 0.7-0.9).

Conclusion:

This study highlights the difficulty in achieving 5-year remission in those with recent onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.

Keywords: Cohort; Prognostic factor; Remission; Spondyloarthritis.

Sociodemographic determinants in the evolution of pain in inflammatory rheumatic diseases: results from ESPOIR and DESIR cohorts

Un nouvel article scientifique intitulé «Sociodemographic determinants in the evolution of pain in inflammatory rheumatic diseases: results from ESPOIR and DESIR cohorts» a été publié dans le journal Rheumatology (Oxford).

Kumaradev S, Roux C, Sellam J, Perrot S, Pham T, Dugravot A, Molto A.

Objective:

To determine whether sociodemographic factors are associated with heterogeneity in pain evolution in inflammatory rheumatic diseases (IRDs) after accounting for disease-specific characteristics in a system with universal health care.

Methods:

This analysis included the data from two prospective observational cohorts of early IRDs (ESPOIR for early rheumatoid arthritis (RA) and DESIR for early spondyloarthritis (SpA)). Data on pain was measured respectively at 13 and 9 occasions spanning 10 and 6 years of follow-up using Short-Form 36 bodily pain amongst 810 participants of ESPOIR, and 679 participants of DESIR. Linear mixed models were used to characterise differences in pain evolution as a function of age (tertiles), sex, ethnicity, education, marital, and professional status after accounting for disease-related, treatment, lifestyle, and health factors.

Results:

While transitioning from early (disease duration ≤6 months for RA and ≤3 years for SpA) to long-standing disease, differences in pain evolution emerged as a function of age (p< 0.001), sex (p= 0.050), and ethnicity (p= 0.001) in RA, and as a function of age (p= 0.048) in SpA; younger age, males, and Caucasians exhibited lower pain in the latter phases of both diseases. Highly educated (RA, β=-3.8, p= 0.007; SpA, β=-6.0, p< 0.001) in both diseases, and Caucasians (β=-5.6, p= 0.021) in SpA presented with low pain early in the disease, with no changes throughout disease course.

Conclusion:

Those older, females, non-Caucasians and lowly educated have worse pain in early and/or long-standing IRDs despite universally accessible health-care. Early identification of at-risk population and implementation of multi-disciplinary strategies may reduce patient-reported health outcome disparities.

Keywords: Pain evolution; pain outcome; rheumatoid arthritis; sociodemographic factors; spondyloarthritis.

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.