Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity - a randomized controlled trial.
Adverse drug reaction
Cytopenia
Folinic acid
Leucovorin
Methotrexate
Neutropenia
Overdose
Poisoning
Randomized controlled trial
Toxicity
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
19 05 2023
19 05 2023
Historique:
received:
04
11
2022
accepted:
20
04
2023
medline:
22
5
2023
pubmed:
20
5
2023
entrez:
19
5
2023
Statut:
epublish
Résumé
Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h. Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. CTRI/2019/09/021152. Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan-Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups. There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.
Sections du résumé
BACKGROUND
Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h.
METHODS
Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery.
TRIAL REGISTRATION NUMBER
CTRI/2019/09/021152.
RESULTS
Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan-Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups.
CONCLUSION
There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.
Identifiants
pubmed: 37208770
doi: 10.1186/s13075-023-03054-2
pii: 10.1186/s13075-023-03054-2
pmc: PMC10197821
doi:
Substances chimiques
Leucovorin
Q573I9DVLP
Methotrexate
YL5FZ2Y5U1
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
82Informations de copyright
© 2023. The Author(s).
Références
Int J Rheum Dis. 2010 Oct;13(4):288-93
pubmed: 21199463
J Egypt Natl Canc Inst. 2022 Apr 18;34(1):17
pubmed: 35434757
Int J Rheum Dis. 2017 Jul;20(7):846-851
pubmed: 28261918
Rheumatology (Oxford). 2005 Aug;44(8):1051-5
pubmed: 15901903
Expert Opin Biol Ther. 2010 Jan;10(1):105-11
pubmed: 19925307
Arch Dermatol. 1971 Jan;103(1):33-8
pubmed: 5539502
J Biol Chem. 1948 Oct;176(1):165-73
pubmed: 18886154
PLoS One. 2016 Apr 29;11(4):e0154744
pubmed: 27128679
Trans Am Clin Climatol Assoc. 2013;124:16-25
pubmed: 23874006
Semin Arthritis Rheum. 1985 Nov;15(2):119-26
pubmed: 3877983
Arthritis Rheum. 1996 Feb;39(2):272-6
pubmed: 8849378
Indian Dermatol Online J. 2019 Jan-Feb;10(1):64-68
pubmed: 30775303
Oncologist. 2016 Dec;21(12):1471-1482
pubmed: 27496039
J Rheumatol Suppl. 1985 Dec;12 Suppl 12:3-6
pubmed: 3913774
J Am Med Assoc. 1957 Aug 31;164(18):2047
pubmed: 13462726
Int J Rheum Dis. 2018 Aug;21(8):1557-1562
pubmed: 30146743