Tumour Necrosis Factor Inhibitor Dose Adaptation in Psoriatic Arthritis and Axial Spondyloarthritis (TAPAS)

A Retrospective Cohort Study

Celia A. J. Michielsens; Nathan den Broeder; Michelle L. M. Mulder; Frank H. J. van den Hoogen; Lise M. Verhoef; Alfons A. den Broeder


Rheumatology. 2022;61(6):2307-2315. 

In This Article

Abstract and Introduction


Objectives: We investigated the effect of disease activity-guided dose optimization (DAGDO) of TNF inhibitor (TNFi) on disease activity and TNFi dose in PsA and axial spondyloarthritis (axSpA) patients with low disease activity (LDA).

Methods: A retrospective cohort study was conducted in PsA and axSpA patients doing well on TNFi and eligible for TNFi DAGDO. Three different treatment periods were defined: (i) full dose continuation period, (ii) TNFi DAGDO period, and (iii) period with stable TNFi dose after DAGDO. A mixed-model analysis was used to estimate mean Disease Activity Score 28-joint count CRP (DAS28-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) during these periods, and a mean percentage of the daily defined dose (%DDD) was calculated as secondary outcome.

Results: Three hundred and twenty-four patients (153 PsA and 171 axSpA) were included, with a mean of 6.5 DAS28-CRP and 6.4 BASDAI measurements and a median follow-up duration of 46 and 44 months, respectively. A corrected difference of 0.06 (95% CI: −0.09, 0.21) in mean DAS28-CRP was found for the TNFi DAGDO period and 0.03 (95% CI: −0.14, 0.20) for the period with stable TNFi dose, compared with full dose continuation period. Differences for BASDAI were 0.03 (95% CI: −0.21, 0.27) and 0.05 (95% CI: −0.24, 0.34), respectively. The mean %DDD for the three treatment periods was for PsA 108%, 62% and 78%, and for axSpA 108%, 62% and 72%, respectively.

Conclusion: DAGDO of TNFi reduces drug exposure and has no negative effects on disease activity in PsA and axSpA patients compared with full dose continuation.


TNF inhibitors (TNFi) have proven safe and effective in the treatment of spondyloarthritis (SpA), including PsA and axial spondyloarthritis (axSpA).[1,2] However, these drugs also have disadvantages such as an increased risk of infections, injection site reactions and the self-administration burden for patients, and high costs.[3–6] Disease activity-guided dose optimization (DAGDO) until complete withdrawal or flare could be a way to reduce these disadvantages.[4] However, there is still uncertainty concerning the effects of DAGDO and discontinuation of TNFi in PsA and axSpA patients with stable low disease activity (LDA) on long-term disease control and safety.

In RA, DAGDO of TNFi has been shown to be safe and (cost-)effective in multiple high quality trials[7,8] and this strategy has been endorsed in recent recommendations.[9] For PsA and axSpA, both the evidence and recommendations are less clear. In PsA, no randomized controlled trials (RCTs) have been performed on DAGDO. One systematic review favoured DAGDO over discontinuation because of the substantial risk of losing remission of the latter.[10] Similar conclusions were derived from observational studies[11–14] and one recently published RCT on discontinuation in ixekizumab.[15]

For axSpA, two systematic reviews[16,17] and six RCTs[18–23] are available. The evidence is in line with that in PsA: TNFi reduction strategies are successful in maintaining clinical remission or LDA in a relevant proportion of patients, but discontinuation is dissuaded because it often leads to flares. However, the conducted studies in both PsA and axSpA investigate the possibility of fixed dose reduction or discontinuation often early after TNFi induction instead of DAGDO in patients with stable LDA. Literature on stepwise DAGDO strategies in prevalent PsA and axSpA patients is still lacking, with three randomized controlled trials on stepwise DAGDO strategies still ongoing.[24–26] Sample size is often an issue in these studies, with relatively small groups of patients participating in dose reduction or discontinuation and limited follow-up. Therefore, long-term follow-up data and a larger patient sample of DAGDO to explore the feasibility and efficacy in daily clinical practice is needed.

DAGDO or discontinuation of bDMARDs as a standard of care in adults with stable axSpA is currently discouraged by the ACR. These recommendations are, however, based on low quality evidence, which predominantly consists of observational studies with no direct comparison of tapered with non-tapered treatment, different patient selection (active disease at baseline) or a lack of DAGDO strategies.[27] The European Alliance of Associations for Rheumatology (EULAR) adopts a different view on tapering and discontinuation in PsA and axSpA. Considering the cost aspect, the guideline deems it appropriate to slowly taper bDMARDs in case of sustained remission.[28,29] In summary, there is a lack of evidence regarding DAGDO in PsA and axSpA.

Since 2010, a specific TNFi DAGDO protocol has been implemented at our outpatient clinic for RA as well as for PsA and axSpA patients, together with standardized measurement of Disease Activity Score28-CRP (DAS28-CRP) in RA, and PsA patients and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in axSpA patients. This allowed us to perform a controlled retrospective cohort study to explore the effect of DAGDO in a real life setting with regards to disease activity, (concomitant) medication use or switching, flare and infection rate.