Background Methotrexate use is known to be associated with acute pneumonitis, an acute hypersensitivity reaction, with a prevalence currently ranging from 0.5%–1%. Some clinicians also have concerns that methotrexate use can also cause direct lung toxicity leading to pulmonary fibrosis. We wanted to study the 10 year effect of methotrexate use on the incidence of pulmonary fibrosis.

Method All patients commenced on methotrexate in our unit between 2004–2007 were evaluated retrospectively from our NHS trust database. Data was collected from electronic case notes and care stream radiological images.

Incidence of pulmonary fibrosis was based on clinical presentation with symptoms of dyspnoea and confirmation by means of chest x-ray, and detection of pulmonary fibrosis on chest high resolution CT scanning.

Results Data for 129 patients was analysed. 63/129 (49%) patients completed 10 years of Methotrexate treatment at follow up. Methotrexate was used for various indications; RA (106), inflammatory arthritis(IA) (7), psoriatic arthritis (6) and others (10). 60/106 (57%) patients with RA were started on methotrexate within 1 year of diagnosis and 46/106 (44%), this was delayed by 1 year or more.

4/129 (3.1%) patients developed pulmonary fibrosis. All cases of pulmonary fibrosis were in RA patients and the incidence in RA sub group was 4/106 (3.8%), all were male and 75% were seropositive for rheumatoid factor. Mean duration of RA at the time of onset of pulmonary fibrosis (PF) was 7.8 years (2 – 15).

Interestingly 3 of 4 patients with PF had commenced MTX over 1 year from diagnosis. Due to the small number of cases this does not reach statistical significance (p=0.2).

Conclusions This is the first 10 year follow up study assessing the incidence of pulmonary fibrosis in patients commenced on methotrexate. Sixty three patients have had 10 or more years of MTX therapy. All cases of pulmonary fibrosis were in patients with RA and the incidence rate at 4% are comparable to previous studies on RA associated PF (4%–7%). No association was found to exposure to MTX. This confirms the previous shorter term studies that there is no evidence that methotrexate causes chronic pulmonary fibrosis.