Background/Purpose:

DRESS, a randomized controlled strategy trial (RCT)¹investigating disease activity guided tapering of etanercept and adalimumab compared to usual care in RA patients, indicated that minimal radiographic progression is more frequent in patients who attempted TNF inhibitor (TNFi) tapering. Possible explanations include higher mean disease activity, higher incidence of flaring, and/or lower TNFi use in the tapering group.

Methods:

Eighteen months data from the DRESS study were used. Change in Sharp van der Heijde (SvdH) score and percentage of patients with minimal progression (> 0.5 SvdH points) were used as outcomes. Mean time averaged disease activity (Disease Activity Score, DAS28CRP), occurrence and number of (major) flares per patient (flare definition DAS28CRP increase > 1.2, of > 0.6 and current DAS28CRP ≥3.2; major flare lasting > 12 weeks), and TNFi use (normalized percentage of the defined daily dose) during the study were used as independent variables. First, the independent contributions of the four disease activity measures were assessed by univariate and multivariate analyses. Thereafter, linear regression modeling was done with SvdH change as dependent variable, to assess the independent contribution of the disease activity measures and TNFi use, controlled for possible confounders including age, sex, BMI, smoking, baseline SvdH score, DAS28CRP, CRP, RF and ACPA status, and concomitant sDMARDs.

Results:

All patients with 18 months data available (n=175) were included. Mean SvdH change was 0.75 and 0.15, and minimal radiographic progression was found in 39/121 (32%) and 9/59 (15%) patients in tapering and usual care group respectively (both p<0.05, number needed to harm [NNH]=6). Mean DAS28CRP and cumulative incidence of (major) flares were 2.3 (SD 0.5) and 2.1 (0.6) and 73% (12%) and 27% (10%) in tapering and usual care (p<0.05). Mean disease activity, but not incidence or number of (major) flares, was independently associated with radiographic progression. No confounding was present.

Conclusion:

The TNFi tapering strategy used in DRESS leads to higher risk for radiographic progression after 18 months than usual care. This is mainly caused by somewhat higher mean disease activity, but not so much by flaring after dose reduction attempts or lower TNFi use itself. Dose tapering of TNFi still seems a safe long-term approach, but long term disease activity should be kept on the lowest level possible using treat to target, and radiologic progression should be checked regularly.

Table 1: linear regression model

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tumor-necrosis-factor-inhibitor-tapering-induced-radiographic-progression-is-driven-by-weighted-mean-disease-activity-over-time-not-flaring-or-lower-tnfi-exposition/