ABSTRACT
Background: Traditionally, biologics are maintained lifelong at standard dose in patients with infammatory arthritis (IA) when sustained low disease activity (LDA) is reached. However, evidence of possible tapering is emerging but data on the optimal approach is lacking. Objectives: The primary outcomes at 18 months follow-up are: Superiority: The proportion of patients reduced to ≤50% of their baseline biologic dose. Equivalence: Disease activity (rheumatoid arthritis [RA] and psoriatic arthritis [PsA]: Disease Activity Score28-C-Reactive Protein [DAS28-CRP] and axial spondyloarthritis [axSpA]: Ankylosing Spondylitis Disease Activity Score [ASDAS]). Methods: The BIODOPT trial was a randomised, open-label, equivalence trial (EudraCT 2017-001970-41). Eligible patients were adults with RA, PsA, or axSpA in LDA on stable biologic doses during ≥12 months. The randomisation ratio was 2:1 (tapering:continuation) stratifed by diagnosis, centre, and repeated biologic failures. In the tapering group, the biologic dosing interval was prolonged by 25% every four months until fare or discontinuation. The continuation group was kept on their baseline biologic dosing interval;however, a small increase was allowed (as usual practise) if requested by the patient. The sample size calculation was based on a pre-defned equivalence margin of ±0.5 disease activity points (<half of the minimal important difference in DAS28-CRP [>1.2] or ASDAS [>1.1]) yielding a power of 87% for 180 enrolled patients. All analyses were based on the intention-to-treat population. Continuous outcomes were analysed with repeated-measures linear mixed-effects models with group, diagnosis, centre, repeated biologic failures, time point, and the interaction between group and time as fxed factors and the baseline value of the relevant variable as a covariate. Categorical outcomes were analysed using logistic regression with missing data imputed as trial failures. Results: Between May, 2018, and March, 2020, 142 patients were enrolled of which 95 were randomised to tapering and 47 to continuation;inclusion was closed in April 2020 due to national implications of the coronavirus pandemic. At 18 months, signifcantly more patients in the tapering group (35 patients [(37%]) achieved a signifcant reduction in their biologic dose (≥50%) compared to the continuation group (one patient [2%]), absolute risk difference (RD) 35%, 95%CI: 24% to 45%, p<0.0001, Table 1. Furthermore, disease activity at 18 months was within the equivalence margins of ±0.5, mean difference between groups 0.08, 95%CI:-0.12 to 0.29;Table 1 and Figure 1. Flares were more frequent in the tapering group (39 [41%] vs 10 [21%], RD 0.20, 95%CI: 0.04 to 0.35, p=0.011) but managed with rescue therapy (e.g. biologic dose escalation or glucocorticoids) as only one patient (1%) in the tapering group and three patients (6%) in the continuation group lost therapeutic response and were switched to another biological agent. Conclusion: Across IA conditions, a signifcant reduction of biologic dose is possible with disease activity-guided tapering while maintaining a similar disease activity state compared to continuation of biologic as usual care.