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.

Keywords: Antirheumatic Agents; Arthritis, Rheumatoid; Epidemiology.

Figure 1

Comparison of profiles of treatment intake in the weighted cumulative exposure combined models. bDMARD, biological disease-modifying antirheumatic drug; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DMARD, disease-modifying antirheumatic drug.

Figure 2

Flowchart of participants in the study. ACR, American College of Rheumatology; DAS28, Disease Activity Score in 28 Joints; ESPOUR, Etude et Suivi des Polyarthrites Indifférenciées Récentes; HAQ, Health Assessment Questionnaire.

Figure 3

Exposure to treatments during the 10-year follow-up in the (A) favourable outcome group (n=418) and the (B) absence of structural damage progression group (n=343). bDMARD, biological disease-modifying antirheumatic drug; csDMARD, conventional synthetic disease-modifying antirheumatic drug.

Figure 4

Results of the weighted cumulative exposure combined model for favourable outcome. bDMARD, biological disease-modifying antirheumatic drug; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DAS28, Disease Activity Score in 28 Joints; ESR, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire Disability Index; vSHS, Sharp-van der Heijde Score.

Figure 5

Receiver operating characteristic curve analysis of multivariate models. (A) Favourable outcome. (B) Absence of structural damage progression. AUC, area under the curve; BIT, binary treatment model; BSL, baseline model; WCE, weighted cumulative exposure.

Figure 6

Results of the weighted cumulative exposure combined model for absence of structural damage progression. ACPA, anticitrullinated peptide antibody; bDMARD, biological disease-modifying antirheumatic drug; CRP, C reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DMARD, disease-modifying antirheumatic drug; vSHS, Sharp-van der Heijde Score.