Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study

Landewé, R.; Sieper, Joachim; Mease, Philip J.; Inman, Robert D.; Lambert, Robert G.; Deodhar, A.; Marzo‐Ortega, Helena; Magrey, Marina; Kiltz, Uta; Wang, Xin; Li, Mei; Zhong, Shaomin; Mostafa, Nael M.; Lertratanakul, Apinya; Pangan, Aileen L.; Anderson, J.

doi:10.1016/s0140-6736(18)31362-x

Cited by 80 publications

(71 citation statements)

References 28 publications

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“…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.…”

Section: Patientsmentioning

confidence: 80%

“…The study received ethical approval from the CMO region Arnhem Nijmegen (NL66181.091. 18) and has been registered in the Dutch Trial Register (NTR 7640). Privacy of patients is protected according to Dutch law AVG (Algemene Verordening Gegevensbescherming), by using anonymized data and restricting access to patient identification logs.…”

Section: Ethical Considerationsmentioning

confidence: 99%

“…We assume that both treatment arms have a prevalence of LDA state of 0.8 (80%) at 12 months, thus assuming 20% will lose LDA in both groups, as expected due to regression to the mean, based on previous research and clinical practice [18,20]. We expect that dose optimisation will cause more (short-lived) flares, however we do not anticipate a permanent loss of LDA state after a T2T strategy with compared without a tapering attempt, because of the short longevity of the flares before reinstatement of the TNFi.…”

Section: Sample Size Considerations and Statistical Analysesmentioning

confidence: 99%

“…The question arises whether the placebo group would have fewer flares if adalimumab was tapered instead of abruptly stopped. Interestingly, predictors for maintaining drug-free remission were not identified [18].…”

Section: Introductionmentioning

confidence: 99%

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

Michielsens¹,

Boers

Broeder

et al. 2020

Trials

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Background: Tumour necrosis factor inhibitors (TNFi) are effective in the treatment of patients with spondyloarthritis (SpA), including psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). However, these drugs come with some disadvantages such as adverse events, practical burden for patients and high costs. Dose optimisation of TNFi after patients have reached low disease activity (LDA) has been shown feasible and safe in rheumatoid arthritis (RA). However, data on TNFi dose optimisation in PsA and axSpA are scarce, especially pragmatic, randomised strategy studies. Methods: We developed an investigator-driven, pragmatic, open-label, randomised, controlled, non-inferiority trial (DRESS-PS) to compare the effects of a disease activity-guided treat-to-target strategy with or without a tapering attempt in patients with SpA (PsA and axSpA combined), ≥ 16 years of age, who are being treated with TNFi, and have had at least 6 months of low disease activity. The primary outcome is the percentage of patients in LDA after 12 months of follow up. Patients are assessed at baseline, 3, 6, 9, and 12 months of follow up. Bayesian power analyses with a weakened prior based on a similar study performed in RA resulted in a sample size of 95 patients in total. Discussion: More knowledge on disease activity-guided treatment algorithms would contribute to better treatment choices and cost savings and potentially decrease the risk of side effects. In this article we elucidate some of our design choices on TNFi dose optimisation and its clinical and methodological consequences.

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Section: Patientsmentioning

confidence: 80%

Section: Ethical Considerationsmentioning

confidence: 99%

Section: Sample Size Considerations and Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Michielsens¹,

Boers

Broeder

et al. 2020

Trials

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“…After 40 weeks of follow-up, 70% of patients in the adalimumab group and 47% of patients in the placebo group remained without disease reactivation (defined as ASDAS≥2.1). The difference of 23% in the incidence of flare-ups at 40 weeks corresponds to a number needed to harm (NNH) of reactivation after withdrawal of 4.3 (95% CI 2.9-7.9) [216] (1B).…”

Section: Biological Therapy Discontinuationmentioning

confidence: 99%

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis – 2019

et al. 2020

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Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013. A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed. These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis. The purpose of these guidelines is to bring evidencebased information on clinical management of axial SpA patients, including, diagnosis, treatment and prognosis, for rheumatologists, general physicians, allied-specialists (dermatology, ophthalmology and gastroenterology), and other allied-professionals, such as physiotherapists. This version replaces the previous guidelines published on May 26, 2013 [3] and should be updated every 4 years. Methods A systematic literature review was performed, with external review of an specialized group of the Brazilian

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Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Lawson

Eraso

Mbuagbaw

et al. 2021

Arthritis Care & Research

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Objective The present study was undertaken to investigate the effectiveness and safety of dose reduction of tumor necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (SpA) compared to usual care. Methods We searched the Cochrane Central Register of Controlled Trials, Embase, Medline, and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random‐effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure, and follow‐up duration. Outcomes of interest were Assessment of SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse, and safety. Results We included 6 randomized trials with 747 participants (442 with ankylosing spondylitis and 305 with nonradiographic axial SpA). Compared to the standard dose, there were fewer events with the reduced dose for the ASAS criteria for 40% improvement (risk ratio [RR] 0.62 [95% confidence interval (95% CI) 0.49, 0.78]) and for ASAS partial remission (RR 0.17 [95% CI 0.06, 0.46]). There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35 [95% CI 0.10, 0.60]) and no difference in C‐reactive protein levels (MD 0.16 [95% CI –0.76, 1.07]) with the reduced dose. There were more disease flares/relapses (RR 1.73 [95% CI 1.32, 2.27]) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98 [95% CI 0.76, 1.25]) or injection/infusion reactions (IRR 0.71 [95% CI 0.42, 1.19]). Conclusion Patients with axial SpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.

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Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study

Cited by 80 publications

References 28 publications

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

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

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis – 2019

Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

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