Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study

AbstractThis multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) including baricitinib (BAR) and tofacitinib (TOF) in patients with RA. Patients were as follows; females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories. The drug retention was evaluated at 24 months using the Kaplan–Meier method and multivariate Cox proportional hazards modelling adjusted by confounders. Discontinuation rates for the corresponding reasons were as follows; ineffectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior history of anti-interleukin-6 receptor antibody (aIL-6R) ineffectiveness significantly increased the risk of treatment discontinuation due to ineffectiveness (p = 0.020). Aging (≥ 75 years) (p = 0.028), usage of PSL ≥ 5 mg/day (p = 0.017) and female sex (p = 0.041) significantly increased the risk of treatment discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, difference of JAKi, and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.

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Factors Affecting Drug Retention of Janus kinase Inhibitors in Patients with Rheumatoid Arthritis: The ANSWER Cohort Study

10.21203/rs.3.rs-744939/v1 ◽

2021 ◽

Author(s):

Kosuke Ebina ◽

Toru Hirano ◽

Yuichi Maeda ◽

Wataru Yamamoto ◽

Motomu Hashimoto ◽

...

Keyword(s):

Adverse Events ◽

Kinase Inhibitors ◽

Retention Rate ◽

Janus Kinase ◽

Tnf Inhibitor ◽

Janus Kinase Inhibitors ◽

Factors Affecting ◽

Female Sex ◽

Drug Retention ◽

Prior Use

Abstract Background: This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) baricitinib (BAR) and tofacitinib (TOF) in patients with RA.Methods: Patients were included as follows: females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185) and concomitant glucocorticoid (prednisolone [PSL] equivalent) 5.3 mg/day (46.7%) or methotrexate (MTX) 8.9 mg/week (60.7%); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories: lack of effectiveness, toxic adverse events, non-toxic reasons and remission. The drug retention rate was estimated at 24 months using the Kaplan–Meier method and adjusted for potential confounders using multivariate Cox proportional hazards modelling.Results: Adjusted discontinuation rates for the corresponding reasons were as follows: lack of effectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior use of anti-interleukin-6 receptor antibody (aIL-6R) was significantly associated with discontinuation due to lack of effectiveness (P = 0.021). Ageing (P = 0.015), usage of PSL ≥5 mg/day (P = 0.017) and female sex (P = 0.041) were significantly associated with discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, different JAKi and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.Conclusions: Prior use of aIL-6R was associated with discontinuation due to lack of effectiveness, while ageing (≥75 years), PSL usage ≥5 mg/day, and female sex were associated with discontinuation due to toxic adverse events.

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Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis

Modern Rheumatology ◽

10.1093/mr/roab003 ◽

2021 ◽

Author(s):

Kosuke Ebina

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Elderly Patients ◽

Kinase Inhibitors ◽

Janus Kinase ◽

Treatment Recommendation ◽

Efficacy And Safety ◽

Old Patients ◽

Janus Kinase Inhibitors ◽

Increased Risk

ABSTRACT Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.

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Systematic review: adverse events with Janus kinase inhibitors

Reactions Weekly ◽

10.1007/s40278-020-74134-8 ◽

2020 ◽

Vol 1788 (1) ◽

pp. 11-11

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Kinase Inhibitors ◽

Janus Kinase ◽

Janus Kinase Inhibitors

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Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis -The ANSWER cohort study-

10.21203/rs.2.22147/v2 ◽

2020 ◽

Author(s):

Kosuke Ebina ◽

Toru Hirano ◽

Yuichi Maeda ◽

Wataru Yamamoto ◽

Motomu Hashimoto ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Disease Duration ◽

Kinase Inhibitors ◽

Certolizumab Pegol ◽

Janus Kinase ◽

Retention Rates ◽

Drug Discontinuation ◽

Naive Group ◽

Drug Retention

Abstract Background: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA). Methods: This study assessed 3,897 patients and 4,415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2,737 bDMARDs-naïve patients and 1,678 bDMARDs-switched patients [59.5% switched to their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [42.4%], and methotrexate [MTX] dose 8.5 mg/week [60.9%]). Treatment courses included abatacept (ABT; n=663), adalimumab (ADA; n=536), certolizumab pegol (CZP; n=226), etanercept (ETN; n=856), golimumab (GLM; n=458), infliximab (IFX; n=724), tocilizumab (TCZ; n=851), and TOF (n=101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using the Gray’s test, and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model. Results: Cumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P<0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P<0.001 between agents). Toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P<0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P=0.004 between agents). Remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P<0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P=0.9 between agents). Conclusions: Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.

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