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

Michielsens, Celia A J; Boers, Nadine; Broeder, Nathan den; Wenink, Mark H.; Maas, Aatke van der; Mahler, E.; Mulder, Michelle L M; Heijde, Desirée van der; Hoogen, F.H.J. van den; Verhoef, Lise M; Broeder, Alfons A den

doi:10.1186/s13063-019-4000-5

Cited by 14 publications

(8 citation statements)

References 45 publications

(58 reference statements)

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“…This meets the acceptable noninferiority margin of an absolute difference of 15% in the cumulative flare rate that was determined by consensus of BACK-OFF JSpA site PIs. This non-inferiority margin is also in accordance with other recent published TNFi dose reduction trials [ 27 – 30 ]. To test our secondary hypothesis, which is that the TNFi stop arm is inferior to each of other two arms (standard TNFi dose and fixed longer TNFi dosing), the logrank test achieves 80% power at a 0.025 significance level (to adjust for multiple comparisons of the secondary hypotheses) to detect a difference of 3.2 in the hazard ratio .…”

Section: Interventionssupporting

confidence: 91%

Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial

Weiss

Sears

Brandon

et al. 2023

Trials

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Background The effectiveness of biologic therapies, primarily tumor necrosis factor inhibitors (TNFi), for children with spondyloarthritis (SpA) has made inactive disease a realistic patient outcome. However, biologic therapies are costly, primarily delivered by subcutaneous or intravenous route, and have non-trivial side effects. Many patients and families want to know if biologic medications can be discontinued after inactive disease is achieved. It remains unclear whether medication dose should remain unchanged, tapered (increase the time between doses), or discontinued once when inactive disease is attained. Methods The Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile SpA (BACK-OFF JSpA) trial is a multicenter pragmatic trial that will randomize 198 participants ages 8–21 years old with SpA and sustained inactive disease on standard TNFi dosing to (1) continue standard TNFi dosing, (2) fixed longer dosing intervals of TNFi, or (3) stop TNFi. The trial will compare the hazard rate of protocol-defined flare and participants’ emotional health among the 3 groups over 12 months. Innovative aspects of this trial are the involvement of patient and parent stakeholders in the design and conduct of the study as well as an electronic health record-based enhanced recruitment strategy. Discussion This is the first randomized pragmatic trial to assess the efficacy of TNFi de-escalation strategies in children with JSpA with sustained inactive disease. This research will improve the evidence base that patients, caregivers, and rheumatologists use to make shared decisions about continued treatment versus de-escalation of TNFi therapy in this population. Trial registration ClinicalTrials.gov NCT04891640. Registered on 18 May 2021.

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Section: Interventionssupporting

confidence: 91%

Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial

Weiss

Sears

Brandon

et al. 2023

Trials

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“…Few studies have evaluated potential predictors of treatment-free remission in spondyloarthritis [ 12 , 13 ]. According to some reports, the factors associated with improved response to therapy include younger age, more severe inflammation, shorter disease duration, male sex, non-smoking status, and rapid response to treatment, although it remains unclear whether these factors are associated with treatment-free remission [ 14 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry

et al. 2023

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Background The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. Methods An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. Results The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91–0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34–0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01–1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21–5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02–0.53). Conclusions Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.

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“…For axSpA, LDA was defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <2.1 for axSpA and/or according to the treating rheumatologist and patient). The study rationale and design were extensively described before17 and are further explained in online supplemental appendix 1.…”

Section: Methodsmentioning

confidence: 99%

“…Flare was defined for PsA by a current PASDAS >3.2 or increase of ≥0.817, and for axSpA as a current ASDAS≥2.1 or increase of ≥0.9 points 18. For both diseases, a flare was also noted when an important worsening of mBSA or active extra-musculoskeletal symptoms (as judged by the treating rheumatologist) occurred.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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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.

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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

Cited by 14 publications

References 45 publications

Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial

Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry

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

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