Co‐prescription of low‐dose methotrexate and trimethoprim‐sulfamethoxazole and the 30‐day risk of death among older adults: A cohort study

Aims The aim of this study was to characterize the risk of death in older adults co‐prescribed low‐dose methotrexate and TMP‐SMX vs. low‐dose methotrexate and a cephalosporin. Methods We conducted a retrospective, population‐based, new‐user cohort study in Ontario, Canada (April 1, 2002–August 1, 20...

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Published inBritish journal of clinical pharmacology Vol. 91; no. 4; pp. 1263 - 1271
Main Authors Sadeghi, Hasti, Ahmadi, Fatemeh, McArthur, Eric, Sontrop, Jessica M., Abdullah, Sheikh S., Urquhart, Brad L., Kim, Richard B., Muanda, Flory T.
Format Journal Article
LanguageEnglish
Published England John Wiley and Sons Inc 01.04.2025
Subjects
Aged
Aged, 80 and over
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - adverse effects
antifolate
cephalosporins
Cephalosporins - administration & dosage
Cephalosporins - adverse effects
Cohort Studies
dosage
Drug Therapy, Combination
drug–drug interaction
Female
Hospitalization - statistics & numerical data
Humans
low‐dose methotrexate
Male
Methotrexate - administration & dosage
Methotrexate - adverse effects
Ontario - epidemiology
Original
Propensity Score
Retrospective Studies
toxicity
Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage
Trimethoprim, Sulfamethoxazole Drug Combination - adverse effects
trimethoprim‐sulfamethoxazole
Ontario
toxicity
dosage
drug–drug interaction
trimethoprim‐sulfamethoxazole
low‐dose methotrexate
cephalosporins
antifolate
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Abstract Aims The aim of this study was to characterize the risk of death in older adults co‐prescribed low‐dose methotrexate and TMP‐SMX vs. low‐dose methotrexate and a cephalosporin. Methods We conducted a retrospective, population‐based, new‐user cohort study in Ontario, Canada (April 1, 2002–August 1, 2022) using linked administrative healthcare data. Older adults taking low‐dose methotrexate who were newly co‐prescribed TMP‐SMX (n = 1602) were matched 1:1 with those who were newly co‐prescribed a cephalosporin. The primary outcome was death within 30 days of the antibiotic dispensing date. Secondary outcomes included all‐cause hospitalization, a hospital visit with myelosuppression and a hospitalization with persistent infection defined as the main diagnosis. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RR) were obtained using modified Poisson regression. Results In a propensity‐score matched cohort of 3204 adults taking low‐dose methotrexate, the 30‐day risk of death was similar in adults co‐prescribed TMP‐SMX vs. a cephalosporin (14/1602 [0.87%] vs. 15/1602 [0.94%]; RR 0.93 [95% CI 0.45–1.93]). The risk of all‐cause hospitalization (RR 1.49 [95% CI 1.13–1.97]) and infection (RR 2.78 [95% CI 1.30–5.95]) was higher in adults treated with TMP‐SMX than those treated with cephalosporins. Conclusions In older adults taking low‐dose methotrexate, co‐prescription of TMP‐SMX vs. a cephalosporin was not associated with a higher 30‐day risk of death but was associated with a higher 30‐day risk of all‐cause hospitalization and hospital admission with persistent infection. If verified, these risks should be balanced against the benefits of co‐prescribing TMP‐SMX and low‐dose methotrexate.
AbstractList The aim of this study was to characterize the risk of death in older adults co-prescribed low-dose methotrexate and TMP-SMX vs. low-dose methotrexate and a cephalosporin.AIMSThe aim of this study was to characterize the risk of death in older adults co-prescribed low-dose methotrexate and TMP-SMX vs. low-dose methotrexate and a cephalosporin.We conducted a retrospective, population-based, new-user cohort study in Ontario, Canada (April 1, 2002-August 1, 2022) using linked administrative healthcare data. Older adults taking low-dose methotrexate who were newly co-prescribed TMP-SMX (n = 1602) were matched 1:1 with those who were newly co-prescribed a cephalosporin. The primary outcome was death within 30 days of the antibiotic dispensing date. Secondary outcomes included all-cause hospitalization, a hospital visit with myelosuppression and a hospitalization with persistent infection defined as the main diagnosis. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RR) were obtained using modified Poisson regression.METHODSWe conducted a retrospective, population-based, new-user cohort study in Ontario, Canada (April 1, 2002-August 1, 2022) using linked administrative healthcare data. Older adults taking low-dose methotrexate who were newly co-prescribed TMP-SMX (n = 1602) were matched 1:1 with those who were newly co-prescribed a cephalosporin. The primary outcome was death within 30 days of the antibiotic dispensing date. Secondary outcomes included all-cause hospitalization, a hospital visit with myelosuppression and a hospitalization with persistent infection defined as the main diagnosis. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RR) were obtained using modified Poisson regression.In a propensity-score matched cohort of 3204 adults taking low-dose methotrexate, the 30-day risk of death was similar in adults co-prescribed TMP-SMX vs. a cephalosporin (14/1602 [0.87%] vs. 15/1602 [0.94%]; RR 0.93 [95% CI 0.45-1.93]). The risk of all-cause hospitalization (RR 1.49 [95% CI 1.13-1.97]) and infection (RR 2.78 [95% CI 1.30-5.95]) was higher in adults treated with TMP-SMX than those treated with cephalosporins.RESULTSIn a propensity-score matched cohort of 3204 adults taking low-dose methotrexate, the 30-day risk of death was similar in adults co-prescribed TMP-SMX vs. a cephalosporin (14/1602 [0.87%] vs. 15/1602 [0.94%]; RR 0.93 [95% CI 0.45-1.93]). The risk of all-cause hospitalization (RR 1.49 [95% CI 1.13-1.97]) and infection (RR 2.78 [95% CI 1.30-5.95]) was higher in adults treated with TMP-SMX than those treated with cephalosporins.In older adults taking low-dose methotrexate, co-prescription of TMP-SMX vs. a cephalosporin was not associated with a higher 30-day risk of death but was associated with a higher 30-day risk of all-cause hospitalization and hospital admission with persistent infection. If verified, these risks should be balanced against the benefits of co-prescribing TMP-SMX and low-dose methotrexate.CONCLUSIONSIn older adults taking low-dose methotrexate, co-prescription of TMP-SMX vs. a cephalosporin was not associated with a higher 30-day risk of death but was associated with a higher 30-day risk of all-cause hospitalization and hospital admission with persistent infection. If verified, these risks should be balanced against the benefits of co-prescribing TMP-SMX and low-dose methotrexate.
Aims The aim of this study was to characterize the risk of death in older adults co‐prescribed low‐dose methotrexate and TMP‐SMX vs. low‐dose methotrexate and a cephalosporin. Methods We conducted a retrospective, population‐based, new‐user cohort study in Ontario, Canada (April 1, 2002–August 1, 2022) using linked administrative healthcare data. Older adults taking low‐dose methotrexate who were newly co‐prescribed TMP‐SMX (n = 1602) were matched 1:1 with those who were newly co‐prescribed a cephalosporin. The primary outcome was death within 30 days of the antibiotic dispensing date. Secondary outcomes included all‐cause hospitalization, a hospital visit with myelosuppression and a hospitalization with persistent infection defined as the main diagnosis. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RR) were obtained using modified Poisson regression. Results In a propensity‐score matched cohort of 3204 adults taking low‐dose methotrexate, the 30‐day risk of death was similar in adults co‐prescribed TMP‐SMX vs. a cephalosporin (14/1602 [0.87%] vs. 15/1602 [0.94%]; RR 0.93 [95% CI 0.45–1.93]). The risk of all‐cause hospitalization (RR 1.49 [95% CI 1.13–1.97]) and infection (RR 2.78 [95% CI 1.30–5.95]) was higher in adults treated with TMP‐SMX than those treated with cephalosporins. Conclusions In older adults taking low‐dose methotrexate, co‐prescription of TMP‐SMX vs. a cephalosporin was not associated with a higher 30‐day risk of death but was associated with a higher 30‐day risk of all‐cause hospitalization and hospital admission with persistent infection. If verified, these risks should be balanced against the benefits of co‐prescribing TMP‐SMX and low‐dose methotrexate.
The aim of this study was to characterize the risk of death in older adults co-prescribed low-dose methotrexate and TMP-SMX vs. low-dose methotrexate and a cephalosporin. We conducted a retrospective, population-based, new-user cohort study in Ontario, Canada (April 1, 2002-August 1, 2022) using linked administrative healthcare data. Older adults taking low-dose methotrexate who were newly co-prescribed TMP-SMX (n = 1602) were matched 1:1 with those who were newly co-prescribed a cephalosporin. The primary outcome was death within 30 days of the antibiotic dispensing date. Secondary outcomes included all-cause hospitalization, a hospital visit with myelosuppression and a hospitalization with persistent infection defined as the main diagnosis. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RR) were obtained using modified Poisson regression. In a propensity-score matched cohort of 3204 adults taking low-dose methotrexate, the 30-day risk of death was similar in adults co-prescribed TMP-SMX vs. a cephalosporin (14/1602 [0.87%] vs. 15/1602 [0.94%]; RR 0.93 [95% CI 0.45-1.93]). The risk of all-cause hospitalization (RR 1.49 [95% CI 1.13-1.97]) and infection (RR 2.78 [95% CI 1.30-5.95]) was higher in adults treated with TMP-SMX than those treated with cephalosporins. In older adults taking low-dose methotrexate, co-prescription of TMP-SMX vs. a cephalosporin was not associated with a higher 30-day risk of death but was associated with a higher 30-day risk of all-cause hospitalization and hospital admission with persistent infection. If verified, these risks should be balanced against the benefits of co-prescribing TMP-SMX and low-dose methotrexate.
Author Sadeghi, Hasti
McArthur, Eric
Urquhart, Brad L.
Muanda, Flory T.
Ahmadi, Fatemeh
Abdullah, Sheikh S.
Sontrop, Jessica M.
Kim, Richard B.
AuthorAffiliation 1 Department of Biology Western University London ON Canada
3 Department of Epidemiology & Biostatistics Western University London ON Canada
6 Division of Clinical Pharmacology, Department of Medicine Western University London ON Canada
2 ICES Toronto ON Canada
4 Lawson Health Research Institute, London Health Sciences Centre London Ontario Canada
5 Department of Physiology and Pharmacology Western University London Ontario Canada
AuthorAffiliation_xml – name: 4 Lawson Health Research Institute, London Health Sciences Centre London Ontario Canada
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Issue 4
Keywords toxicity
dosage
drug–drug interaction
trimethoprim‐sulfamethoxazole
low‐dose methotrexate
cephalosporins
antifolate
Language English
License Attribution-NonCommercial
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2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Notes Funding information
This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long‐Term Care (MLTC).
The findings of this manuscript were initially presented as an abstract at The Canadian Society of Pharmacology and Therapeutics meeting held in Ottawa from June 16 to June 19, 2024.
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Funding informationThis study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long‐Term Care (MLTC).
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Snippet Aims The aim of this study was to characterize the risk of death in older adults co‐prescribed low‐dose methotrexate and TMP‐SMX vs. low‐dose methotrexate and...
The aim of this study was to characterize the risk of death in older adults co-prescribed low-dose methotrexate and TMP-SMX vs. low-dose methotrexate and a...
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StartPage 1263
SubjectTerms Aged
Aged, 80 and over
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - adverse effects
antifolate
cephalosporins
Cephalosporins - administration & dosage
Cephalosporins - adverse effects
Cohort Studies
dosage
Drug Therapy, Combination
drug–drug interaction
Female
Hospitalization - statistics & numerical data
Humans
low‐dose methotrexate
Male
Methotrexate - administration & dosage
Methotrexate - adverse effects
Ontario - epidemiology
Original
Propensity Score
Retrospective Studies
toxicity
Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage
Trimethoprim, Sulfamethoxazole Drug Combination - adverse effects
trimethoprim‐sulfamethoxazole
Title Co‐prescription of low‐dose methotrexate and trimethoprim‐sulfamethoxazole and the 30‐day risk of death among older adults: A cohort study
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fbcp.16365
https://www.ncbi.nlm.nih.gov/pubmed/39647844
https://www.proquest.com/docview/3146583045
https://pubmed.ncbi.nlm.nih.gov/PMC11992661
Volume 91
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