Tapering Order of csDMARDs and TNF Inhibitors Does Not Affect Flare Rates in RA

senior woman with arthritis holding prescription medicine pill bottle
There are no differences in terms of rheumatoid arthritis flares when TNF inhibitors are tapered first vs when csDMARDs are tapered first.

Patients with well-controlled rheumatoid arthritis (RA) who taper their conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) before tapering tumor necrosis factor (TNF) inhibitors do not experience significant differences in flare rates, disease activity, or disability compared with patients who taper their TNF inhibitor before tapering their csDMARD, according to findings from the multicenter Tapering Strategies in Rheumatoid Arthritis (TARA) trial published in the Annals of the Rheumatic Diseases.

In this trial, researchers from the Netherlands used data from patients with RA who were using both a csDMARD and TNF inhibitor. Patients were included in the study only if they had well-controlled RA, which was defined as a Disease Activity Score of ≤2.4 and a swollen joint count of ≤1 at 2 consecutive time points within a 3-month interval. Patients were randomly assigned to 2 different tapering regimens: gradual tapering of the csDMARD followed by tapering of the TNF inhibitor (n=94) or gradual tapering of the TNF inhibitor first followed by tapering of the csDMARD (n=95).

The proportion of patients who experienced a disease flare within the 2-year follow-up period comprised the primary outcome. Additional secondary outcomes included DMARD-free remission, Disease Activity Score, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI), and radiographic progression.

After 24 months, the cumulative flare rates were 61% (95% CI, 50-71) in patients who tapered csDMARD first vs 62% (95% CI, 52-72) in patients who tapered the TNF inhibitor first (P =.84). While a higher percentage of patients who tapered their csDMARD first more often went through the entire tapering protocol (31% vs 21%), there was no statistically significant difference between the 2 groups (P =.12). After 24 months, patients who tapered their csDMARD first reached DMARD-free remission more often than patients who tapered their TNF inhibitor first (20% vs 11%, respectively; P =.07), but the difference was not significant. All patients in both groups reached DMARD-free remission after 18 months.

There were also no differences between the 2 groups in terms of disease activity (P =.45) and functional ability as assessed by the HAQ-DI (P =.17). In addition, no significant differences were found between the tapering regimens in terms of radiographic progression over time (P =.8).

A limitation of the study was the inclusion of some patients who were taking >1 csDMARD and the tapering of only 1 of these csDMARDs, meaning some did not truly reach DMARD-free remission.

Because there were no differences between the 2 tapering protocols in terms of RA flares, the investigators suggested that “financial arguments may influence the decision to taper TNF inhibitors first.”


van Mulligen E, Weel AE, Hazes JM, van der Helm-van Mil A, de Jong PHP. Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial [published online June 1, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-217485