Dose tapering and discontinuation of biological therapy in rheumatoid arthritis patients in routine care – 2-year outcomes and predictors

Brahe, Cecilie Heegaard; Krabbe, Simon; Østergaard, Mikkel; Ørnbjerg, Lykke Midtbøll; Glinatsi, Daniel; Røgind, Henrik; Jensen, Hanne; Hansen, Annette; Nørregaard, Jesper; Jacobsen, Søren; Huynh, Tuan Khai; Jensen, Dorte Vendelbo; Manilo, Natalia; Asmussen, Karsten; Frandsen, P; Boesen, Mikael; Rastiemadabadi, Zoreh; Carlsen, Lone Morsel; Møller, Jakob M.; Krogh, Niels Steen; Hetland, Merete Lund

doi:10.1093/rheumatology/key244

Cited by 33 publications

(25 citation statements)

References 24 publications

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“…Another limitation is the lack of radiologic evaluation. Recent studies have shown that imaging-detected residual synovitis is a predictor for the risk of disease flare after tapering or discontinuing biological DMARDs [37,[43][44][45]. Nevertheless, the present study provides useful information regarding the treatment strategies of tofacitinib, namely, dose reduction, withdrawal, and restart, in RA patients who have achieved sustained disease control in daily clinical practice.…”

Section: Discussionmentioning

confidence: 87%

“…According to the Kaplan-Meier approach, 66% of our patients had experienced disease flares at 12 months. Recent clinical trials and observational studies regarding biological DMARDs, mainly TNF inhibitors, have also suggested that a stepwise tapering strategy until complete withdrawal is preferable to direct withdrawal [30][31][32][33][34][35][36][37]. This strategy seems to be applicable to tsDMARDs such as tofacitinib and baricitinib.…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study

Mori¹,

Ueki

2019

Clin Rheumatol

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Objective This study was designed to compare outcomes of dose reduction, withdrawal, and continuation of tofacitinib in patients with rheumatoid arthritis (RA) and to examine effectiveness of rescue with an original treatment regimen for disease flare. Methods We prospectively enrolled 100 patients who had high or moderate disease activity and treated them with tofacitinib at 5 mg twice daily for 1 year. All patients achieving remission or low disease activity (LDA) were assigned to a withdrawal, dosereduction, or continuation group, then followed until disease flare or end of the study. For flare cases, the original treatment regimen was reintroduced. Results During the first year, 68 patients achieved remission or LDA (median sustained time 49.0 weeks). Subsequently, disease flare occurred at the following crude incidence rates per person-year (95% confidence interval [CI]): 0.73 (0.43-1.22) after withdrawal, 0.44 (0.25-0.77) after dose reduction, and 0.04 (0.01-0.27) during continuation. Kaplan-Meier estimates of median flare-free time (95% CI) were 7.0 months (2.8-11.2) for withdrawal and 21.0 months (4.1-37.9) for dose reduction. In the Cox regression analysis, adjusted hazard ratios (95% CIs) were 18.11 (2.38-138) for withdrawal and 9.13 (1.19-70.4) for dose reduction compared with continuation. Restart of the original treatment regimen led to rapid remission in flare cases (93% for withdrawal and 100% for dose reduction). Conclusion After achievement of remission or LDA, the dose-reduction strategy seems preferable to immediate withdrawal of tofacitinib. Restart of the original regimen can reinduce RA control in flare cases. Key Points • During the 1-year tofacitinib therapy, two-thirds of RA patients with high or moderate disease activity achieved rapid and sustained remission or low disease activity. • During subsequent years, the incidence rate and adjusted hazard ratio for disease flare were significantly higher following tofacitinib immediate withdrawal than following dose reduction. • Half of the patients were estimated to remain flare-free for 21 months after dose reduction and for 7 months after withdrawal of tofacitinib. • Restart of the original treatment regimen rapidly restored disease control in almost all flare cases.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study

Mori¹,

Ueki

2019

Clin Rheumatol

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“…However, US measurements were not accessed in the present study. Recently, the results from the ADOPT guideline (established in the Capital Region of Denmark) have shown that 2/3 of patients with RA in stable remission were able to successfully taper their bDMARDs . Per the ADOPT guideline, bDMARDs were tapered in all RA patients according to a treatment algorithm.…”

Section: Discussionmentioning

confidence: 99%

Dose down‐titration of biological disease‐modifying antirheumatic drugs in daily clinical practice: Shared decision‐making and patient treatment preferences in Japanese patients with rheumatoid arthritis

et al. 2019

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Aim:To determine characteristics of rheumatoid arthritis (RA) patients in Japan who received the same biological disease-modifying antirheumatic drugs (bDMARDs) for at least 6 months and to identify factors associated with successful down-titration of bDMARDs dependent on shared decision-making. Methods:We included consecutive RA patients who received the same bDMARD with low disease activity or remission for at least 6 months in our two university hospitals. Patients treated with the bDMARD standard dose were defined as SD, while those treated with bDMARD down-titration were defined as DT. We retrospectively reviewed clinical charts and compared data between the two groups.Results: Of 288 patients with RA, 204 (70.8%) and 84 (29.2%) continued standard dose treatment and underwent down-titration treatment, respectively. Sixty-six of 84 (78.6%) down-titration-treated patients continued to show low disease activity or remission, whereas 18 (21.4%) relapsed 18.9 ± 24.4 months after bDMARD down-titration was started. Univariate predictor analysis showed that the probable factors of down-titration were no history of bDMARD treatment (P = .001) and low initial Disease Activity Assessment of 28 joint score (P = .048). Other clinical characteristics had no significant relationship with successful down-titration.Conclusions: Thus, bDMARD-naïve patients and those with low initial disease activity are more likely to agree to attempt down-titration. However, the timing and method of down-titration should be made in shared decision-making between patients and rheumatologists. K E Y W O R D Santirheumatic agents, arthritis-rheumatoid, decision-making, guideline, therapeutics

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“…This post‐hoc analysis was based on data from the longitudinal, multicenter, observational cohort ADOPT (A Dose OPTimization of biological therapy) study, using data collected between 8 May, 2013 and 29 September, 2016 from patients with established RA in sustained clinical remission at baseline and in case of a relapse …”

Section: Methodsmentioning

confidence: 99%

Association between MRI findings and patient‐reported outcomes in patients with rheumatoid arthritis in clinical remission and at relapse

et al. 2020

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Objective: To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. Methods: Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. Results: Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P < .01), independent of clinical and radiographic measures, and was also associated with most of the hand-related HAQ items (P < .03). In multivariate models including MRI, SvH scores were not associated with PROs. MRI-assessed inflammation was not associated with PROs at remission or relapse. Conclusion: Magnetic resonance imaging-assessed wrist/hand damage, but not inflammation, in patients with established RA is associated with patient-reported | 489 GLINATSI eT AL. At the baseline and relapse visit, 28 tender and swollen joint counts (TJC/SJC) were performed and blood samples, including CRP, were obtained. The patients also completed health physical impairment at remission and relapse. The amount of damage in the wrist/ hand is associated with reduced hand function. K E Y W O R D S hand, magnetic resonance imaging, rheumatoid arthritis S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Glinatsi D, Brahe CH, Hetland ML, et al. Association between MRI findings and patient-reported outcomes in patients with rheumatoid arthritis in clinical remission and at relapse. Int J Rheum Dis. 2020;23:488-498.

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Dose tapering and discontinuation of biological therapy in rheumatoid arthritis patients in routine care – 2-year outcomes and predictors

Cited by 33 publications

References 24 publications

Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study

Outcomes of dose reduction, withdrawal, and restart of tofacitinib in patients with rheumatoid arthritis: a prospective observational study

Dose down‐titration of biological disease‐modifying antirheumatic drugs in daily clinical practice: Shared decision‐making and patient treatment preferences in Japanese patients with rheumatoid arthritis

Association between MRI findings and patient‐reported outcomes in patients with rheumatoid arthritis in clinical remission and at relapse

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