Background The Dose REduction Strategies of Subcutaneous tumor necrosis factor inhibitors (TNFi) study (DRESS), a randomized controlled strategy trial (RCT) investigating disease activity guided tapering of etanercept and adalimumab compared to usual care in rheumatoid arthritis (RA) patients, indicated that minimal radiographic progression is more frequent in patients that attempted TNFi tapering (1). Possible explanations include higher mean disease activity, higher incidence of flaring, and/or lower TNFi use in the tapering group.
Objectives To investigate possible causes of a difference in minimal radiographic progression between patients that attempted tapering compared to patients that did not attempt to taper TNFi.
Methods Eighteen months data were used. Mean change (Δ) in Sharp van der Heijde score (SvdH) and percentage of minimal radiographic progression, defined as >0.5 ΔSvdH, were calculated and used as outcome. Mean time weighted disease activity using DAS28-CRP (MTW-DAS28-CRP), occurrence and number of (major) flares per patient (flare: DAS28-CRP increase >1.2, or >0.6 and current DAS28-CRP ≥3.2; major flare: lasting >12 weeks), and TNFi use (normalized percentage of the defined daily dose) during the study were used in univariate and multivariate analyses. Thereafter, linear regression modeling was done with ΔSvdH as dependent variable and the above mentioned disease activity measures and TNFi use as independent variables, controlled for possible confounders (including age, sex, BMI, smoking, baseline SvdH, DAS28-CRP, CRP, RF and ACPA status, and concomitant synthetic DMARD). To check for effect modification by randomization group (tapering or usual care), all models were also done for both groups separately.
Results All patients with 18 months data available (n=175) were included. Mean ΔSvdH was 0.75 and 0.15, and minimal radiographic progression was found in 39/121 (32%) and 9/59 (15%) patients in the tapering and usual care group respectively (both p<0.05, number needed to harm [NNH]=6). Mean DAS28-CRP and cumulative incidence of (major) flares were 2.3 (standard deviation [SD] 0.5) versus 2.1 (0.6) and 73% (12%) versus 27% (10%) in tapering and usual care (p<0.05). MTW-DAS28-CRP, but not incidence or number of (major) flares, was independently associated with radiographic progression. Effect modification was present for randomization group (p=0.01) (table 1). No significant confounding was present.
Conclusions 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 time weighted disease activity, but not so much by flaring after dose reduction attempts or lower TNFi use itself. Effect modification by randomization group was present. Dose tapering of TNFi still seems a safe long-term approach, but long term disease activity should be kept on the lowest possible level using treat to target, and radiologic progression should be checked regularly.
Van Herwaarden N et al. BMJ 2015;350:h1389
Disclosure of Interest None declared