PMID- 37211570
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20230718
IS  - 1434-9949 (Electronic)
IS  - 0770-3198 (Linking)
VI  - 42
IP  - 8
DP  - 2023 Aug
TI  - Relationship between frailty and methotrexate discontinuation due to adverse 
      events in rheumatoid arthritis patients.
PG  - 2069-2077
LID - 10.1007/s10067-023-06639-z [doi]
AB  - 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.
CI  - (c) 2023. The Author(s), under exclusive licence to International League of 
      Associations for Rheumatology (ILAR).
FAU - Sobue, Yasumori
AU  - Sobue Y
AUID- ORCID: 0000-0002-8936-4278
AD  - Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, 
      3-35 Michishita, Nakamura, Nagoya, Aichi, 453-8511, Japan. 
      yasumorisobue527@yahoo.co.jp.
FAU - Suzuki, Mochihito
AU  - Suzuki M
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
AD  - Department of Orthopedic Surgery, Japan Community Healthcare Organization Kani 
      Tono Hospital, 1221-5 Dota, Kani, Gifu, 509-0206, Japan.
FAU - Ohashi, Yoshifumi
AU  - Ohashi Y
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
AD  - Department of Orthopedic Surgery, Yokkaichi Municipal Hospital, 2-2-37 Shibata, 
      Yokkaichi, Mie, 510-8567, Japan.
FAU - Koshima, Hiroshi
AU  - Koshima H
AD  - Department of Orthopedic Surgery, Japan Community Healthcare Organization Kani 
      Tono Hospital, 1221-5 Dota, Kani, Gifu, 509-0206, Japan.
FAU - Okui, Nobuyuki
AU  - Okui N
AD  - Department of Orthopedic Surgery, Yokkaichi Municipal Hospital, 2-2-37 Shibata, 
      Yokkaichi, Mie, 510-8567, Japan.
FAU - Funahashi, Koji
AU  - Funahashi K
AD  - Department of Orthopedic Surgery, Kariya Toyota General Hospital, 5-15 Sumiyoshi, 
      Kariya, Aichi, 448-0852, Japan.
FAU - Ishikawa, Hisato
AU  - Ishikawa H
AD  - Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, 
      3-35 Michishita, Nakamura, Nagoya, Aichi, 453-8511, Japan.
FAU - Inoue, Hidenori
AU  - Inoue H
AD  - Department of Orthopedic Surgery, Japanese Red Cross Nagoya Daiichi Hospital, 
      3-35 Michishita, Nakamura, Nagoya, Aichi, 453-8511, Japan.
FAU - Asai, Shuji
AU  - Asai S
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
FAU - Terabe, Kenya
AU  - Terabe K
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
FAU - Kishimoto, Kenji
AU  - Kishimoto K
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
FAU - Kihira, Daisuke
AU  - Kihira D
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
FAU - Maeda, Masataka
AU  - Maeda M
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
FAU - Sato, Ryo
AU  - Sato R
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
FAU - Imagama, Shiro
AU  - Imagama S
AD  - Department of Orthopedic Surgery and Rheumatology, Nagoya University Graduate 
      School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230522
PL  - Germany
TA  - Clin Rheumatol
JT  - Clinical rheumatology
JID - 8211469
RN  - YL5FZ2Y5U1 (Methotrexate)
RN  - 0 (Antirheumatic Agents)
SB  - IM
MH  - Humans
MH  - Female
MH  - Middle Aged
MH  - Aged
MH  - Methotrexate/adverse effects
MH  - *Antirheumatic Agents/adverse effects
MH  - Retrospective Studies
MH  - *Frailty
MH  - *Arthritis, Rheumatoid
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adverse event
OT  - Frailty
OT  - Kihon Checklist (KCL)
OT  - Methotrexate
OT  - Rheumatoid arthritis
EDAT- 2023/05/22 00:41
MHDA- 2023/07/17 06:42
CRDT- 2023/05/21 23:06
PHST- 2023/01/06 00:00 [received]
PHST- 2023/05/13 00:00 [accepted]
PHST- 2023/05/08 00:00 [revised]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/05/22 00:41 [pubmed]
PHST- 2023/05/21 23:06 [entrez]
AID - 10.1007/s10067-023-06639-z [pii]
AID - 10.1007/s10067-023-06639-z [doi]
PST - ppublish
SO  - Clin Rheumatol. 2023 Aug;42(8):2069-2077. doi: 10.1007/s10067-023-06639-z. Epub 
      2023 May 22.