Dataset Information

Positive impact on 10-year outcome of the window of opportunity for conventional synthetic DMARDs in rheumatoid arthritis: results from the ESPOIR cohort.

ABSTRACT:

Objective

This study aimed to assess the impact of disease-modifying antirheumatic drugs (DMARDs) on 10-year outcomes in rheumatoid arthritis (RA).

Methods

Patients with RA from the ESPOIR cohort with complete data on Disease Activity Score in 28 Joints (DAS28) and Health Assessment Questionnaire (HAQ) at 10 years (n=418) and complete radiographic data at baseline and 10 years (n=343) were included in this study. Outcomes were favourable outcome (FavOut) at 10 years, defined as DAS28 of <2.6 and HAQ score of <0.5 at 10 years, and absence of structural damage progression (AbsSDP) at 10 years, defined as change in Sharp-van der Heijde Score less than the smallest detectable change at 10 years (11.5 points). Three multivariate logistic regression models predicting 10-year outcome were built, considering (1) baseline variables only, (2) baseline variables and DMARD exposure (ever exposed, yes/no) and (3) baseline variables and DMARD exposure as weighted cumulative exposure (WCE) variables.

Results

Overall, 196/418 (46.9%) patients showed FavOut and 252/343 (73.5%) AbsSDP. WCE models had the best predictive performance, with area under the curve=0.80 (95% CI 0.74 to 0.87) for FavOut and 0.87 (95% CI 0.83 to 0.92) for AbsSDP. In the WCE model, the odds of FavOut and AbsSDP were reduced with conventional synthetic disease-modifying antirheumatic drug (csDMARD) initiation at 12 months versus at baseline (OR 0.78, 95% CI 0.65 to 0.94, and OR 0.89, 95% CI 0.76 to 0.98, respectively). Early biologics initiation was not significantly associated with either outcome.

Conclusions

WCE models can identify and quantify the long-term benefit of early csDMARD initiation on 10-year functional and structural outcomes in patients with RA.

SUBMITTER: Kedra J

PROVIDER: S-EPMC9086647 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Positive impact on 10-year outcome of the window of opportunity for conventional synthetic DMARDs in rheumatoid arthritis: results from the ESPOIR cohort.

Kedra Joanna J Lafourcade Alexandre A Combe Bernard B Dougados Maxime M Hajage David D Fautrel Bruno B

RMD open 20220501 1

<h4>Objective</h4>This study aimed to assess the impact of disease-modifying antirheumatic drugs (DMARDs) on 10-year outcomes in rheumatoid arthritis (RA).<h4>Methods</h4>Patients with RA from the ESPOIR cohort with complete data on Disease Activity Score in 28 Joints (DAS28) and Health Assessment Questionnaire (HAQ) at 10 years (n=418) and complete radiographic data at baseline and 10 years (n=343) were included in this study. Outcomes were favourable outcome (FavOut) at 10 years, defined as DA ...[more]

PMID: 35534053

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Project description:Background and objectiveEarly seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis.Patients and methodsPatients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes.ResultsOne hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07-5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year.ConclusionOur results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms.Trial registrationClinicalTrials.gov: NCT03666091. Registered September 11, 2018.

Project description:Cycling of biologic or targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA) patients due to non-response is a problem preventing and delaying disease control. We aimed to assess and validate treatment response of b/tsDMARDs among clusters of RA patients identified by deep learning. We clustered RA patients clusters at first-time b/tsDMARD (cohort entry) in the Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) [1999-2018]. We performed comparative effectiveness analyses of b/tsDMARDs (ref. adalimumab) using Cox proportional hazard regression. Within 15 months, we assessed b/tsDMARD stop due to non-response, and separately a ≥20% reduction in DAS28-esr as a response proxy. We validated results through stratified analyses according to most distinctive patient characteristics of clusters. Clusters comprised between 362 and 1481 patients (3516 unique patients). Stratified (validation) analyses confirmed comparative effectiveness results among clusters: Patients with ≥2 conventional synthetic DMARDs and prednisone at b/tsDMARD initiation, male patients, as well as patients with a lower disease burden responded better to tocilizumab than to adalimumab (hazard ratio [HR] 5.46, 95% confidence interval [CI] [1.76-16.94], and HR 8.44 [3.43-20.74], and HR 3.64 [2.04-6.49], respectively). Furthermore, seronegative women without use of prednisone at b/tsDMARD initiation as well as seropositive women with a higher disease burden and longer disease duration had a higher risk of non-response with golimumab (HR 2.36 [1.03-5.40] and HR 5.27 [2.10-13.21], respectively) than with adalimumab. Our results suggest that RA patient clusters identified by deep learning may have different responses to first-line b/tsDMARD. Thus, it may suggest optimal first-line b/tsDMARD for certain RA patients, which is a step forward towards personalizing treatment. However, further research in other cohorts is needed to verify our results.

Dataset Information

Positive impact on 10-year outcome of the window of opportunity for conventional synthetic DMARDs in rheumatoid arthritis: results from the ESPOIR cohort.

Objective

Methods

Results

Conclusions

Publications

Positive impact on 10-year outcome of the window of opportunity for conventional synthetic DMARDs in rheumatoid arthritis: results from the ESPOIR cohort.

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