Methotrexate in sarcoidosis: hematologic and hepatic toxicity encountered in a large cohort over a six year period

BACKGROUND: Methotrexate (MTX) is a second line agent for treatment of sarcoidosis. Its long term safety and efficacy in sarcoidosis remains unclear. METHODS: This was a retrospective review of patients seen at the University of Cincinnati Sarcoidosis Clinic over a six year period. For each visit, complete blood count, liver function testing, and dosing and outcome of MTX was noted. For efficacy, we compared the outcome of therapy of a matching subgroup of patients treated with either MTX or infliximab for one year and results scored as improved, stable, or worse based on response of the target organ. RESULTS: Over six years, 1606 sarcoidosis patients were seen with a total of 13,576 clinical visits. During the study period, 607 patients (38% of total) were receiving MTX and had available blood work. Moderate elevation of alanine aminotransferase (ALT) (>3 times upper limit normal) was seen in nine (1.6%) patients. White blood count of <1500 cells per cu mm was seen in one patient. At six months, over half of the 44 patients initiated on infliximab and with at least six months of follow-up were better, while only 23% of the 44 of a matched subset of MTX treated patients were better (Chi square=10.566, p=0.0143). At the 12 month assessment, the infliximab treated patients were still more likely to be better than those treated with MTX (Chi square=10.033, p=0.0183). Only 23% of those treated with MTX were worse at twelve months. CONCLUSION: In our study, MTX therapy was associated with very few hepatic or hematologic complications. MTX was less likely than infliximab to improve clinical status. However, only 20% were worse after one year of MTX. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (3): e2020001)