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Relationship between frailty and methotrexate discontinuation due to adverse events in rheumatoid arthritis patients
Yasumori Sobue1, Mochihito Suzuki2,3, Yoshifumi Ohashi2,4
1Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, 3-35 Michishita, Nakamura, Nagoya, Aichi, 453-8511, Japan. yasumorisobue527@yahoo.co.jp.
Introduction:
Methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA). Frailty is the intermediate condition between being healthy and disabled, and can lead to negative health outcomes. Adverse events (AEs) due to RA drugs are expected to be higher in frail patients. The present study aimed to investigate the relationship between frailty and MTX discontinuation due to AEs in RA patients.
Methods:
Of 538 RA patients who visited us between June and August 2020 as part of the retrospective T-FLAG study, 323 used MTX. After 2 years of follow-up, we investigated AEs leading to MTX discontinuation. Frailty was defined as a Kihon Checklist (KCL) score ≥ 8. Cox proportional hazards regression analysis was performed to identify factors associated with MTX discontinuation due to AEs.
Results:
Of the 323 RA patients (251 women, 77.7%) who used MTX, 24 (7.4%) discontinued MTX due to AEs during the 2-year follow-up period. Mean ages in the MTX continuation/discontinuation groups were 64.5 ± 13.9/68.5 ± 11.7 years (p = 0.169), Clinical Disease Activity Index was 5.6 ± 7.3/6.2 ± 6.0 (p = 0.695); KCL was 5.9 ± 4.1/9.0 ± 4.9 points (p < 0.001); and the proportion of frailty was 31.8%/58.3% (p = 0.012). MTX discontinuation due to AEs was significantly associated with frailty (hazard ratio 2.34, 95% confidence interval 1.02-5.37) even after adjusting for age and diabetes mellitus. AEs included liver dysfunction (25.0%), pneumonia (20.8%), and renal dysfunction (12.5%).
Conclusions:
Because frailty is a significant factor contributing to MTX discontinuation due to AEs, the latter should be carefully monitored in frail RA patients who use MTX. Key Points • Of the 323 rheumatoid arthritis (RA) patients (251 women, 77.7%) who used methotrexate (MTX), 24 (7.4%) discontinued MTX due to adverse events (AEs) during the 2-year follow-up period. • MTX discontinuation due to AEs was significantly associated with frailty (hazard ratio 2.34, 95% confidence interval 1.02-5.37) even after adjusting for age and diabetes mellitus, and neither the MTX dose, folic acid supplementation, nor GC co-therapy were factors in MTX discontinuation. • Frailty is a predominant factor in MTX discontinuation among established, long-term pretreated RA patients, and the occurrence of AEs due to MTX should be carefully monitored when frail RA patients use MTX.
Insights
Frailty significantly increases the risk of methotrexate discontinuation due to adverse events in rheumatoid arthritis patients. Careful monitoring of frail individuals on methotrexate is crucial for managing potential side effects.
Area of Science:
- Rheumatology
- Gerontology
- Clinical Pharmacology
Background:
- Methotrexate (MTX) is a primary treatment for rheumatoid arthritis (RA).
- Frailty, a state of increased vulnerability, is linked to adverse health outcomes.
- Frail patients may experience higher rates of adverse events (AEs) from RA medications.
Purpose of the Study:
- To investigate the association between frailty and MTX discontinuation due to AEs in RA patients.
- To identify risk factors for MTX discontinuation in a cohort of RA patients.
Main Methods:
- Retrospective study of 323 RA patients using MTX from the T-FLAG study.
- Follow-up over 2 years to assess MTX discontinuation due to AEs.
- Frailty assessed using the Kihon Checklist (KCL) score (≥8); Cox proportional hazards regression used for analysis.
Main Results:
- 24 out of 323 (7.4%) RA patients discontinued MTX due to AEs.
- MTX discontinuation was significantly associated with frailty (HR 2.34, 95% CI 1.02-5.37), independent of age and diabetes.
- Common AEs leading to discontinuation included liver dysfunction (25.0%), pneumonia (20.8%), and renal dysfunction (12.5%).
Conclusions:
- Frailty is a significant predictor of MTX discontinuation due to AEs in RA patients.
- Close monitoring for AEs is recommended for frail RA patients treated with MTX.
- Frailty, not MTX dose, folic acid, or GC co-therapy, was a predominant factor in discontinuation.
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