This observational cohort study evaluated whether extending MTX lab monitoring from every 3 months (45–135 days) to every 6 months (135–225 days) affects timely detection of toxicity (CBC and LFTs) in 2,439 patients across 14,199 lab encounters.
Testing frequency had no meaningful correlation with changes in ALT, AST, WBC, HCT, MCV, PLT, or FIB-4 (all R² < 0.01). After propensity score matching, 6-month monitoring was not associated with worse outcomes; patients in the 6-month group were actually *less* likely to develop ALT >1× ULN (OR 0.72, 95% CI 0.52–0.99) or MCV >100 fL (OR 0.67, 95% CI 0.46–0.96).
Observational design limits causal inference; propensity score matching may not fully control for confounding (e.g., clinicians may select healthier patients for less frequent monitoring). The study does not capture rare but severe toxicity events that may require longer follow-up.
For stable patients on MTX, extending routine lab monitoring to every 6 months appears safe and does not delay toxicity detection — clinicians can consider moving away from quarterly testing to reduce cost and patient burden. This may prompt a reassessment of the current ACR-recommended 3-month monitoring interval.
