Journal Article

Treat-to-target dose reduction and withdrawal strategy of TNF inhibitors in psoriatic arthritis and axial spondyloarthritis: a randomised controlled non-inferiority trial

Verhoef, Lise M, den Broeder, Alfons A, Teerenstra, Steven, Mahler, Elien AM, Michielsens, Celia AJ, van den Hoogen, Frank HJ, den Broeder, Nathan, van der Heijde, Désirée

2022

Overview

ObjectivesTumour necrosis factor inhibitors (TNFi) are effective in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), but are associated with a small (0.6%) increase in serious infection risk, patient burden due to need for self-injection and high costs. Treat-to-target (T2T) tapering might ameliorate these drawbacks, but high-quality evidence on T2T tapering strategies is lacking in PsA and axSpA.MethodsWe performed a pragmatic open-label, monocentre, randomised controlled non-inferiority (NI) trial on T2T tapering of TNFi. Patients with PsA and axSpA using a TNFi with ≥6 months stable low disease activity (LDA) were included. Patients were randomised 2:1 to disease activity-guided T2T with or without tapering until withdrawal and followed-up to 12 months. Primary endpoint was the difference in proportion of patients having LDA at 12 months between groups, compared with a prespecified NI margin of 20%, estimated using a Bayesian prior.Results122 patients (64 PsA and 58 axSpA) were randomised to a T2T strategy with (N=81) or without tapering (N=41). The proportion of patients in LDA at 12 months was 69% for the tapering and 73% for the no-tapering group: adjusted difference 5% (Bayesian 95% credible interval: −10% to 19%) which confirms NI considering the NI margin of 20%. The mean percentage of daily defined dose was 53% for the tapering and 91% for the no-tapering group at month 12.ConclusionsA T2T TNFi strategy with tapering attempt is non-inferior to a T2T strategy without tapering with regard to the proportion of patients still in LDA at 12 months, and results in a substantial reduction of TNFi use.Trial registration numberNL 6771.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Antirheumatic Agents - therapeutic use / Arthritis / Arthritis, Psoriatic / Arthritis, Psoriatic - drug therapy / Axial Spondyloarthritis / Bayes Theorem / Bayesian analysis / Clinical medicine / Decision making / Disease / Drug dosages / Drug Tapering / Drug withdrawal / Humans / Inflammatory diseases / Outpatient care facilities / Patients / Psoriatic arthritis / Quality of life / Rheumatic diseases / Rheumatoid arthritis / Rheumatology / Spondylarthritis - drug therapy / Spondylitis, Ankylosing / TNF inhibitors / Treatment Outcome / Tumor necrosis factor / Tumor Necrosis Factor Inhibitors / Tumor Necrosis Factor Inhibitors - therapeutic use / Tumor necrosis factor-TNF / Tumors