Disease activity-guided dose optimization including discontinuation of TNF inhibitors in rheumatoid arthritis is effective for up to 10 years: an observational follow-up of the DRESS study

Abstract

Objective: The objective of this study was to investigate the safety and effectiveness of disease activity-guided dose optimization of TNF inhibitors in RA over 10 years.

Methods: The study involved an observational long-term extension of a randomized study of participants who completed the 3-year extension of the DRESS-study. After the randomized phase (months 0-18), disease activity-guided dose optimization was allowed for all. The main outcomes were mean time-weighted DAS28-CRP; biologic and targeted synthetic DMARD (b/tsDMARD) use per year, as proportion of daily defined dose; proportion of patients reaching discontinuation; durability and effectiveness of subsequent dose reduction attempts; and radiographic progression between years 3 and 10 using the Sharp-van der Heijde score.

Results: A total of 170 patients were included, of whom 127 completed the 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% CI 2.10-2.16), while the b/tsDMARD dose reduced from 97% at baseline (95% CI 96-99%, n = 170) to 56% at year 10 (95% CI 49-63%, n = 127). Of 161 participants with an optimization attempt, 119 (74%) reached discontinuation with a median duration of 7 months (interquartile range 3-33 months), and 25 participants never had to restart their b/tsDMARD (21%, 95% CI 14-29%). The mean dose reduction after dose optimization was 48% (n = 159) for the first optimization attempt, and 33% for a subsequent attempt (n = 86). Of the 86 participants, 41 (48%) had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use.

Conclusion: Long-term disease activity-guided dose optimization of TNF inhibitors in RA, including discontinuation and multiple tapering attempts, remains safe and effective.

Keywords: TNF inhibitors; adalimumab; biologics; dose reduction; etanercept; rheumatoid arthritis; tapering.

Figure 1.

Study flowchart. ^aRepresents the number of patients with ≥1 DAGDO attempt. ^bRepresents the number of patients with ≥1 discontinuation attempt. At least one disease activity measurement was required to be included in the analyses. DAGDO: disease activity–guided dose optimization; DRESS: Dose REduction Strategy of Subcutaneous TNF inhibitors study; LTE: long-term extension study (3 year follow-up); TNFi: TNF inhibitor

Figure 2.

Represents the drug dose relative to the daily defined dose (%DDD) per subsequent year (for all b/tsDMARDs and DRESS TNFis), and the proportion of patients on DRESS TNFi using co-medication (for csDMARD and prednisolone). ^aNumber also applicable for csDMARD and prednisolone. b/ts DMARD: biologic/targeted synthetic DMARD; csDMARD: conventional synthetic DMARD; DRESS: Dose REduction Strategy of Subcutaneous TNF inhibitors study; TNFi: TNF inhibitor

Figure 3.

Mean time-weighted disease activity per year measured with DAS28-CRP

Figure 4.

Survival of first discontinuation attempt of the DRESS TNFi in years. The upticks represent censored subjects. DRESS: Dose REduction Strategy of Subcutaneous TNF inhibitors study; TNFi: TNF inhibitor