Introduction
Rheumatoid arthritis (RA) is a chronic condition characterised by periods of remission alternated with disease reactivations (ie, flares). Though RA treatment options are rapidly growing, glucocorticoids are still frequently used to treat inflammation and manage disease activity. The 2019 European League Against Rheumatism (EULAR) recommendations for the therapy of RA strongly urge tapering glucocorticoids to the lowest dose achievable. However, tapering strategies are primarily based on expert opinion or personal conviction, and it is uncertain whether continuous low-dose glucocorticoid therapy can offer significant benefits that outweigh the drawbacks of such an approach. At three years, nearly 50% of individuals with early RA are able to discontinue glucocorticoids, but within the following six months, about 30% of these people experience a flare. While it is true that tapering and stopping glucocorticoids has been linked to an increased risk of flare, the dosage at which the flare occurs is unpredictable and frequently unknown. Furthermore, the EULAR definition of low-dose glucocorticoids (i.e., 7.5mg/day) is arbitrary and founded on questionable assumptions that are mostly focused on the frequency of side events rather than on efficacy in treating disease activity. The primary objective of this study is to describe and determine the dose–response association between glucocorticoid tapering and risk of flare in RA.
Methods
We conducted a case-crossover study to determine the factors associated with higher risk of flare in patients with RA. In case-crossover studies time-varying factors are assessed before events (hazard periods) and before control periods. We defined hazard periods as the 6 months immediately preceding flares of RA. Control periods were the 6 months prior to visits without flare. Exposure of interest was the tapering of glucocorticoids to various doses. Glucocorticoid tapering was further categorised into
(1) tapering to 0mg/day (ie, discontinuation),
(2) tapering to 0–2.5mg/day,
(3) tapering to 2.5–5mg/ day,
(4) tapering to 5–7.5mg/day and
(5) tapering to ≥7.5mg/day.
Results
508 patients with RA were included in the study and 267 (52.5%) had at least a flare and served as the case-crossover study population. 1545 visits were available for analysis and 345 (22.3%) flares were recorded. Discontinuation of glucocorticoids (ie, tapering to doses of 0mg/day) and tapering to 0–2.5mg/day was associated with higher risk of flare (adjusted OR (aOR) of 1.45, 95% CI: 1.13 to 2.24 and aOR of 1.37; 95% CI: 1.06 to 2.01, respectively). Tapering to doses >2.5mg/- day was not associated with significantly higher risk of flare.
Conclusions
We found that tapering to doses of >2.5mg/ day was generally effective in terms of risk of flare. Flare risk was higher when glucocorticoids were tapered to doses ≤2.5mg/day. Our study might help design new tapering strategies in patients with RA on biological disease-modifying antirheumatic drugs.
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