Background/Purpose: Long-term observational studies on the prediction of structural damage progression (SDP) in rheumatoid arthritis (RA) have mostly considered patients baseline characteristics and have rarely evaluated the specific impact of treatments in real world settings.

The objective of this study was to assess the impact of treatment exposure on the 10-year radiographic progression in early rheumatoid arthritis (RA).

Methods: The 310 patients of the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort fulfilling ACR/EULAR 2010 criteria at baseline and having complete radiographic data at baseline and 10 years were considered in the present study. SDP was defined at 10 years as a significant increase of the Sharp/van der Heijde score, i.e., superior to the Smallest Detectable Change (SDC) of 11.5 at 10 years. Three RA treatments were considered: glucocorticoids (GC), conventional synthetic and biologic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs and bDMARDs), which posologies were standardized by the mean of dose quotients (DoseQ). Drug exposure was modelled with Weighted Cumulative Exposure (WCE) variables [1], considering the intensity of drug exposure defined as a weighted function of past doses, and was incorporated into a logistic regression model that also included baseline clinical, biological and radiological characteristics. The predictive performance of this WCE model was compared to models considering on the one hand only baseline characteristics (BSL model) and on the other, baseline characteristics and binary treatments exposure – in other terms, “ever exposed, yes or no” (BIT model).

Results: Overall, SDP at 10 years occurred in 85 (27.4%) patients. In the final WCE model, the combined exposure to 1 DoseQ of csDMARD and 1 DoseQ of bDMARD during the 10-year follow-up was associated with a significant protective effect on SDP compared to patients receiving no treatment: OR=0.04 (95% CI: 0.002-0.72). Early csDMARD initiation, i.e., as soon as the cohort inclusion was associated with a significantly lower risk of SDP compared to later initiation (after month 3 or more) (Table 1).

Initiation of a bDMARD between the 3rd month and 3rd year of follow-up in combination with a csDMARD was not significantly superior to early csDMARD initiation (Table 1).

The final WCE model was better at predicting SDP at 10 years compared to the BSL and BIT models: AUC=0.92 (95% CI: 0.89-0.95), AUC=0.85 (95% CI: 0.80-0.89) and AUC=0.87 (95% CI: 0.83-0.91) respectively (Figure 1).

Of note, GC exposure was significantly associated with SDP only in the univariate analysis and did not remain significant when baseline characteristics are considered.

Conclusion: CsDMARDs and bDMARDs have a protective effect on radiographic progression at 10 years in RA patients. This effect is better captured by the WCE model compared to models with binary treatments exposure and should be more frequently used in further studies.

[1] Dixon WG, Abrahamowicz M, Beauchamp ME et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infectious in older patients with rheumatoid arthritis: a nested case-control analysis. Ann Rheum Dis 2012;71(7):1128-33.

Table 1: Odd ratios for the association of patterns of drug regimen with 10-year radiographic progression

Figure 1: Receiver Operating Characteristic curves of BSL model (A), BIT model (B) and WCE combined model (C) for 10-year radiographic progression

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-treatments-on-radiographic-progression-over-the-first-10-years-of-disease-in-early-rheumatoid-arthritis-results-from-the-espoir-cohort/