Discontinuation of tofacitinib and TNF inhibitors in patients with rheumatoid arthritis: analysis of pooled data from two registries in Canada

Movahedi, Masoud; Choquette, D.; Coupal, Louis; Cesta, Angela; Li, Xiuying; Keystone, Edward; Bombardier, Claire; Investigators, Obri

doi:10.1136/bmjopen-2022-063198

Cited by 3 publications

(3 citation statements)

References 39 publications

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“…We then showed that none of the potential predictors of therapy discontinuation considered, including patient age, previous treatment with biologics, concomitant use of csDMARD, and positivity for RF and/or ACPA, were statistically significant after regression analysis. Similar data were reported by Bilgin et al [ 33 ], Movahedi et al [ 34 ], Bird et al [ 35 ], and Finckh et al [ 36 ], who found no relevant predicting factor for TOFA discontinuation. Our results are also in agreement with a recently published paper analyzing data from a Korean registry, in which no predictive factors for discontinuation of therapy were found, except RF and ACPA positivity, both of which were associated with higher drug retention rates [ 37 ].…”

Section: Discussionsupporting

confidence: 88%

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Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Paroli,

Becciolini,

Bravi

et al. 2023

Medicina

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Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan–Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8–91.5%) at month 12, 78.8% (95% CI: 78.8–85.2%) at month 24, 63.8% (95% CI: 55.1–73.8%) at month 36, and 59.9% (95% CI: 55.1–73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

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Section: Discussionsupporting

confidence: 88%

“…It has been reported from a Turkish study, in which the TOFA retention rate was 63.9% at 1 year [ 33 ]. In another study, Movahedi et al found a drug retention rate of 63.3% at a mean follow-up of 23.2 months [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Paroli,

Becciolini,

Bravi

et al. 2023

Medicina

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“…In an observational cohort study, patients with RA receiving JAKis did not demonstrate higher rates of discontinuation owing to AEs than those treated with tumor necrosis factor inhibitors (TNFi) did [ 22 ]. In contrast, higher discontinuation rates owing to AEs were observed with tofacitinib than with TNFis in older patients having RA with cardiovascular risk factors [ 23 ]. It was reported that RA with lower cerebrovascular attack-free survival rates had highest disease activity levels at baseline [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis

Saito,

Yoshida,

Ebina

et al. 2024

PLoS ONE

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Background Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA. Methods We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan–Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model. Results Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001). Conclusions In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity.

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Early identification of golimumab-treated patients with higher likelihood of long-term retention

García-Dorta,

González-Dávila,

Sánchez-Jareño

et al. 2024

Front. Immunol.

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BackgroundThe early identification of patients’ profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications.ObjectivesTo evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions.DesignRetrospective non-interventional database analysis.MethodsKaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated.Results885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]).ConclusionWith this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab

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Discontinuation of tofacitinib and TNF inhibitors in patients with rheumatoid arthritis: analysis of pooled data from two registries in Canada

Cited by 3 publications

References 39 publications

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study

Real-world comparative study of drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis

Early identification of golimumab-treated patients with higher likelihood of long-term retention

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