Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis.

Abstract

has been associated with an increased risk of MTX pneumonitis in these studies [6–11]. Meta-analytic methods were used to pool the odds ratio for MTX pneumonitis in the presence of pre-existing lung disease. The summarized data from these six studies are in Table 1. Although these studies varied in their design and definition of pre-existing lung disease, all suggested that it predisposed to MTX pneumonitis (pooled odds ratio of 7.5, 95% confidence interval CI 3.6–15.8). Pre-existing lung disease was seen in 48% of 69 patients who developed MTX pneumonitis. By comparison, only 7.4% of 1769 patients without pneumonitis had evidence of prior lung disease. Kremer and Alarcon et al. [9, 14] described the single largest series of MTX pneumonitis (29 cases) in a retrospective case– control study of RA patients. Pre-existing lung disease, old age and previous use of DMARDs were identified as risk factors for pneumonitis after MTX. Ohosone [11] came to a similar conclusion. Age and previous DMARD use have not been identified as a risk in other studies [6–8, 10]. In a multicentre study [10] of 1162 patients with RA treated with MTX in northeast England, 27 probable cases of pneumonitis were identified, of which 10 met the Searles and McKendry criteria [25] for pneumonitis. Pre-existing pulmonary fibrosis was present in five of these 10 cases of pneumonitis. Our experience in a prospective study [6] of 120 patients with RA treated with MTX identified three cases of pneumonitis. Abnormal lung function tests (less than 70% of the value predicted for age and sex) were found to confer added risk of pneumonitis. A low forced expiratory volume in 1 s (FEV1) and vital capacity (VC) carried a relative risk of 3.2 and a low transfer factor for carbon monoxide (TLCO) carried a relative risk of 10, whereas an abnormal CXR carried a relative risk of 3.3. Golden et al. [7] reported a relative risk of 4 for patients with interstitial infiltrates on CXR.