The effect of treatment with methotrexate for primary biliary cirhossis on lung

Low dose methotrexate treatment (MTX) has been proposed as a potentially promising treatment for primary biliary cirrhosis (PBC), which accounts for many of the liver transplantations in the USA. However, methotrexate treatment has been found to contribute to lower lung function in conditions other than PBC, and if it occurs concomitant with treatment of PBC, could exacerbate the reduced lung function already a characteristic of these patients. We therefore tested for impaired lung function as measured by diffused lung carbon-monoxide (DLCO) during a long term randomized placebo control trial of MTX on PBC. No significant impairment of the mean change in DLCO (baseline – minimum) were found between placebo or MTX groups for early (-0.65, (-1.94, 0.64), p=0.1605) or advanced (0.16, (-1.12, 1.44), p=0.5972) PBC liver stages. Likewise, no statistically significant effect of MTX was detected using the ratio of geometric means: (-3.74%, (-11.59%, 3.56%), p=0.3206) and (1.85%, (-5.47%, 8.65%), p=0.3991), respectively. An exploratory analysis considering duration of treatment also could not reveal a significant impairment of DLCO in patients grouped by shorter than or longer than 6 years of MTX treatment. In conclusion, this study was unable to establish evidence of lung toxicity by MTX among early or advanced stage PBC patients.