Possible association of low dose methotrexate therapy for rheumatoid arthritis with chronic pulmonary fibrosis

ABSTRACT

Low dose methotrexate [MTX] treatment is used extensively as a second-line therapy in RA. Two forms of interstitial lung diseases are related to low dose MTX therapy, the first is acute methotrexate pneumonitis which is a life-threatening complication that occurs in less than 10% of RA patients treated with MTX. The other interstitial lung affection is chronic pulmonary fibrosis [PF]. To evaluate whether chronic PF can be a significant complication in RA patient treated with low dose methotrexate [MTX]. The study was performed on 40 RA patients who fulfilled the American College of Rheumatology classification criteria for RA, The patients were classified into two separate groups. The first group consisted of 20 RA patients who were being treated with low dose MTX at the time of initial assessment, while the other group comprised another 20 RA patients who were not being treated with MTX, but treated with second-line therapy other than MTX. Pulmonary function tests were performed for all patients at the time of initial assessment using the standard protocol. All patients underwent HRCT chest scanning. Supine views were taken in serial slices 10 mm apart and 1 mm in width. According to the study design, the patients were followed over 18 months from the time of the initial assessment. Clinically, the patients were assessed regularly at time intervals of 3 months particularly for development of any chest illness together with the patient compliance of drug therapy and its effect on disease. Follow up chest radiographs and HRCT were performed at the end point. The age of the patients and disease duration in the MTX group were 52.1+ 2.9 years and 8.9 +/- .2 years respectively while in the other group they were 50.8 +/- 2.1 years and 9.2 +/- 5.1 years respectively. Pulmonary function results at baseline assessment expressed no significant differences between the two groups with p value > 0.05. On initial HRCT chest scanning, 3 patients were found to have PF interstitial lung disease pattern, two of them were being treated with MTX. There was no significant difference in the dose and duration of MTX treatment between the two RA patients treated with MTX and has PF on initial evaluation and those who were being treated with the drug and had no evidence of PF on HRCT on chest scanning at the initial evaluation. Change in pulmonary function tests from the time of initial assessment to the end of the study was not clinically or statistically significant in both groups [p value > 0.05]. Furthermore, there was no clinical or pulmonary function evidence that MTX had any deteriorating effect on PF detected in two patients on initial assessment even when compared with the patients who were not being treated with it. This study showed no clinical, physiological or radiological evidence that low dose MTX treatment used successfully in treatment of RA is associated with chronic fibrotic lung disease