Relationship between frailty and methotrexate discontinuation due to adverse events in rheumatoid arthritis patients.

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.

Validation of grip strength as a measure of frailty in rheumatoid arthritis.

Rheumatoid arthritis (RA) patients often exhibit finger/wrist joint symptoms and reduced grip strength. This study aimed to validate grip strength as a measure of frailty in RA patients. Subjects were 424 female RA patients (mean age ± standard deviation, 66.8 ± 14.5 years). Frailty was defined as a score of ≥ 8 points on the Kihon Checklist (KCL). Finger/wrist joint symptoms were defined based on tender or swollen joints. Associations between frailty and grip strength were determined using receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis. There were 179 subjects with frailty (42.2%). Multivariable logistic regression analysis revealed that frailty was significantly associated with grip strength independently of finger/wrist joint symptoms. In ROC curves, cut-off scores of grip strength for frailty in subjects without and with finger/wrist joint symptoms were 17 kg (sensitivity, 62.1%; specificity, 69.0%) and 14 kg (sensitivity, 63.2%; specificity, 73.0%), respectively. The results of the present study suggest that grip strength in female RA patients is associated with frailty, with a cut-off score of 17 kg (equivalent to Cardiovascular Health Study criteria, < 18 kg) when RA patients have no finger/wrist joint symptoms. However, when RA patients have finger/wrist joint symptoms, it may be considered to reduce the cut-off score of grip strength.

Locomotive syndrome in rheumatoid arthritis patients during the COVID-19 pandemic.

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories "GLFS-5" and "Social activities" were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in "Social activities" and that of "GLFS-5." Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00-1.22]) and CDAI (OR: 1.08 [95%CI: 1.00-1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

Influence of frailty on patient global assessment in rheumatoid arthritis.

AIM: Patient Global Assessment (PtGA; range 0-10 cm) is an important indicator of clinical outcomes, including physical function, in self-assessment of patients with rheumatoid arthritis (RA). Frailty is a concept that encompasses not only physical, but also mental, psychological and social vulnerability. This study aimed to investigate the influence of frailty on PtGA in patients with RA. METHODS: Among 581 patients with RA who completed a questionnaire survey on frailty between June and August 2020, 559 who completed the Kihon Checklist (KCL; a 25-item questionnaire with seven domains) were included. The proportion of patients with PtGA ≤1 was compared between the frailty (KCL score ≥8), pre-frailty (KCL score 4-7) and robust (KCL score 0-3) groups. Factors associated with PtGA ≤1 were examined using multivariate logistic regression models. RESULTS: Of the 559 patients, 221 (39.5%) had frailty. The proportion of patients with PtGA ≤1 was significantly lower in the frailty group (33.9%) than in the robust (65.4%, P < 0.001) and pre-frailty (55.7%, P < 0.001) groups. Multivariate analysis revealed that frailty (vs robust, OR 0.37, 95% CI 0.22-0.69), as well as disease duration and tender joint count, were factors independently associated with PtGA ≤1. When each domain of the KCL was examined, activities of daily living, physical strength, isolation and depressive mood were factors associated with PtGA ≤1. CONCLUSION: Frailty affects PtGA in patients with RA. As frailty impacts the physical, mental and social vulnerability aspects of PtGA, a multifaceted approach, including inflammation suppression, is required to improve PtGA in patients with RA. Geriatr Gerontol Int 2022; 22: 399-404.

Relationship between locomotive syndrome and frailty in rheumatoid arthritis patients by locomotive syndrome stage.

OBJECTIVES: This study aimed to evaluate the association between locomotive syndrome (LS) and frailty in rheumatoid arthritis (RA) patients. METHODS: Subjects were 538 RA patients (female, 72.9%; mean age ± standard deviation, 66.8 ± 13.4 years). LS and frailty were defined as ≥16 points on the 25-question Geriatric Locomotive Function Scale (Stage ≥2) and ≥8 points on the Kihon Checklist (KCL), respectively. RESULTS: There were 214 subjects with Stage ≥2 LS (39.8%) and 213 subjects with frailty (39.6%). Among subjects with Stage 0, 1, 2, and 3 LS, 11.0%, 21.9%, 48.3%, and 84.6% had frailty, respectively. The KCL points for cognitive and psychosocial factors had no significant differences across LS stages. Multivariable logistic regression analysis revealed that the Health Assessment Questionnaire was independently associated with frailty and LS stage, and the Clinical Disease Activity Index was associated with LS stage but not frailty. CONCLUSIONS: As LS worsens in RA patients, the likelihood of developing physical frailty increases. RA patients with a low LS stage can still develop frailty, and suppressing disease activity may not be sufficient to prevent frailty. These findings highlight the need to screen for frailty in RA patients and consider appropriate interventions based on each patient's condition, focusing on nonphysical factors.

Expression of interleukin-1beta, cyclooxygenase-2, and prostaglandin E2 in a rotator cuff tear in rabbits.

We investigated the specific factors related to shoulder pain due to a rotator cuff tear using a model in rabbits. A rotator cuff tear was surgically created, and the expression of interleukin-1beta (IL-1beta), prostaglandin E2 (PGE2), and cyclooxygenase-2 (COX-2) was analyzed. In the supernatant of the tissue culture of the torn tendon, IL-1beta production was detected. The amount of IL-1beta was highest 1 day after injury, and then decreased gradually to 21 days. PGE2, the mediator of pain and the product of COX-2, was also detected in the supernatant of the tissue culture. The production of PGE2 significantly increased to 7 days after injury, and then decreased to 21 days. RT-PCR analysis confirmed the mRNA expression of IL-1beta and COX-2 in the torn tendon. Immunohistochemical study demonstrated that cells in the tendon stump were immunopositive for IL-1beta and COX-2. Furthermore, in the affected joint, articular chondrocytes in the remote area from the tear expressed COX-2 strongly. When the rotator cuff is torn, IL-1beta is produced in the torn tendon, and stimulates the expression of COX-2 in not only the torn tendon but also in articular chondrocytes. The COX-2 then produces PGE2, which would mediate shoulder pain.