Loading ...

TOPLINE:

Liver-related adverse drug reactions were nearly three times more common than kidney-related adverse drug reactions in patients with rheumatoid arthritis (RA) using methotrexate; however, fatal outcomes were higher in patients with kidney-related adverse drug reactions than in those with liver-related adverse drug reactions and even worse in those with adverse drug reactions affecting both.

METHODOLOGY:

• Researchers conducted a retrospective study using reports from a European spontaneous reporting system until 2022 to assess the effect of methotrexate and comedications on kidney- and liver-related adverse drug reactions in patients with RA.
• They included 10,319 reports of adverse drug reactions with RA as the indication and methotrexate as the interacting or suspected drug (mean age of patients, 62.3 years; 72.6% women). The median duration of methotrexate use was 13.2 months.
• Comedications included non-steroidal anti-inflammatory drugs (NSAIDs), metamizole, acetaminophen, disease-modifying antirheumatic drugs, corticosteroids, and folic acid.
• Outcomes were categorised as either fatal (resulting in death) or non-fatal, (including life-threatening situations, prolonged hospitalisation, disabilities, congenital anomalies, or other conditions).

TAKEAWAY:

• A total of 365 reports of adverse drug reactions were related to the kidneys, 1082 reports were related to the liver, and 67 reports were related to both the kidneys and the liver.
• Patients with kidney-related adverse drug reactions had a longer duration of methotrexate use (median, 16.2 vs 9.9 months) and more fatal outcomes (21.1% vs 5.8%) than those with liver-related adverse drug reactions.
• Patients with liver-related adverse drug reactions who had fatal outcomes were older than those with non-fatal outcomes (P < .001) and had a more common use of comedications, including corticosteroids (P = .012), acetaminophen (P = .002), metamizole (P = .001), and any comedication (P ≤ .001).
• A higher proportion of patients with adverse drug reactions affecting both the liver and kidneys had fatal outcomes and use of NSAIDs, acetaminophen, or metamizole than those with adverse drug reactions affecting only the kidneys or the liver (P < .001 for all).

IN PRACTICE:

"Because drug management in patients with RA using MTX [methotrexate] is a complex matter, precise and standardised recommendations on when and how frequently renal function needs to be tested to detect early signs of renal impairment might be helpful to prevent fatal outcomes," the authors wrote.

SOURCE:

This study was led by Kai Khoroshun, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany. It was published online on April 05, 2025, in Arthritis Research & Therapy.

LIMITATIONS:

The search strategy in Medical Dictionary for Regulatory Activities may have influenced the distribution of kidney- and liver-related cases. The quality of spontaneous reports was another limitation. The prevalence, risk, or incidence could not be calculated as the total number of methotrexate users was inaccessible.

DISCLOSURES: 

This study did not receive any funding and reported an open access funding that was enabled and organised by Projekt DEAL. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.