The role of liver transaminase levels in methotrexate intolerance in juvenile idiopathic arthritis—a cross-sectional study

• Published in: Rheumatology international Vol. 43; no. 5; pp. 875 - 880
• Main Authors: Wibrand, Camilla, Kyvsgaard, Nini, Christensen, Anne Estmann, Herlin, Troels
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2023; Springer Nature B.V
• Subjects: Alanine Transaminase; Antirheumatic Agents - adverse effects; Arthritis; Arthritis, Juvenile - drug therapy; Child; Children & youth; Cross-Sectional Studies; Female; Girls; Humans; Liver; Male; Medicine; Medicine & Public Health; Methotrexate - adverse effects; Observational Research; Rheumatology; Treatment Outcome; Methotrexate; Liver transaminases; Methotrexate intolerance severity score; Juvenile idiopathic arthritis; Methotrexate intolerance
• ISSN: 1437-160X; 0172-8172; 1437-160X
• DOI: 10.1007/s00296-023-05297-3

Methotrexate (MTX) plays a key role when treating juvenile idiopathic arthritis (JIA), but MTX-intolerance is challenging. MTX-treatment might affect the liver, causing elevated levels of alanine aminotransferase (ALT), yet the role of ALT-levels in MTX-intolerance in JIA remains unclear. Our study aimed to investigate the association between ALT-levels during MTX-treatment and MTX-intolerance in JIA. Children (> 9 years old) diagnosed with JIA and treated with MTX (> 6 weeks) were eligible for enrollment. MTX-intolerance was assessed using the Methotrexate Intolerance Severity Score (MISS), completed by the parents, and defined as MISS ≥ 6 with at least 1 point for a behavioral/anticipatory/associative symptom. ALT-levels were determined at enrollment. A total of 118 children were enrolled (80 girls; 38 boys). MTX-intolerance was registered in 61%. ALT-levels did not differ between the MTX-intolerant group (median = 17.0 U/L [IQR: 14.0–26.0]) and the MTX-tolerant group (median = 20.5 U/L [IQR: 16.0–27.5]; p  = 0.17). MTX-intolerance was prevalent in around 60% of both boys and girls. Nine out of 50 MTX-intolerant girls had elevated ALT-levels compared to 0/22 MTX-intolerant boys, however, there was no difference in median ALT levels between the two groups. Furthermore, the MTX-intolerant girls had a higher MISS (median = 14.0 [IQR: 9.3–17]) than the MTX-intolerant boys (median = 10.0 [IQR: 7.3–12]; p  = 0.009). Our study did not find a difference in ALT-levels between MTX-intolerant and MTX-tolerant children. However, only MTX-intolerant girls and no MTX-intolerant boys showed elevated ALT-levels.