Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity

Abstract

Down-titration and discontinuation strategies of tumour necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.

Dose reduction and withdrawal strategy for TNF-inhibitors in psoriatic arthritis and axial spondyloarthritis: design of a pragmatic open-label, randomised, non-inferiority trial

“…Furthermore, PsA and axSpA share pathophysiological, genetic and clinical characteristics, and as current treatment options are almost identical with respect to type of drugs used, dosing and concomitant DMARDs used (Table 1) and finally because preliminary dose optimisation data are similar, we felt this was possible without too much risk of Table 1 Overview of DMARDs in psoriatic arthritis, radiographic axial spondyloarthritis and non-radiographic axial spondyloarthritis different effects in the two diseases. The T2T principle is also already widely pursued in multiple chronic inflammatory disorders, including PsA and axSpA, indicating that this overarching principle seems disease agnostic [9,17,18,22]. Additionally, the outcome of non-inferiority of the tapering strategy is not dependent on the percentage of patients that can taper or stop, but on the implementation of the T2T strategy and the effectiveness of increased or restarted dosing on disease activity, and we do not anticipate effect modification between the two closely related diseases.…”

“…Since this is a non-inferiority design, expectation bias would rather result in inferiority of the tapering group, resulting in a more conservative estimation of the effect. Open-label tapering studies in RA indeed show that successful dose optimisation is achieved in a smaller proportion of patients compared to similar blinded studies [9]. This may in part be due to the patient's fear of decreasing their dose and experiencing a flare, leading to the nocebo effect and incorrect attribution of complaints to the dose optimisation.…”

“…Participants are randomised using a computer-generated procedure, stratified by disease and for use of csDMARDs, to ensure equal distribution and prevent bias. We did not stratify by the different types of TNFi, since we expect a similar mechanism of action while tapering as demonstrated in previous studies [9]. Studies on dose optimisation with different types of TNFi, though mainly including data on adalimumab and etanercept, show no major difference in clinical outcome after dose optimisation or stopping.…”

“…A recent Cochrane review showed that fixed dose reduction (e.g. by 50%) and disease activity-guided dose optimisation for TNFi is comparable to continuation of treatment, although discontinuation without reinstatement of TNFi in the case of a flare seems to be an inferior strategy [9]. Additionally, previous studies have demonstrated the strong cost-effectiveness of tapering in RA [10][11][12].…”

<p>Evaluation of Therapeutic Drug Monitoring in the Clinical Management of Patients with Rheumatic Diseases: Data from a Retrospective Single-Center Cohort Study</p>

“…The TDM algorithms and cut-off values used in this study were based on data from other studies, as well as our experience. [17][18][19][20][21] Trough level cut-off may vary depending on several factors, such as disease nature, phenotype, gender and serum albumin, as well as the measurement method/assay, etc., making it difficult to establish universal ranges. 22 Establishing "true" therapeutic ranges and cut-off levels requires large-scale studies relating concentration to effect, with unbiased measurement of the outcomes.…”