Using subcutaneous methotrexate to prolong duration of methotrexate therapy in rheumatoid arthritis

Our study aims to determine whether the use of subcutaneous methotrexate (SC MTX) is associated with prolonged MTX use and lower incidence of hepatotoxicity in rheumatoid arthritis (RA) patients on MTX monotherapy and multiple drug therapy.

We conducted a retrospective cohort study using national databases of a large hospital system. Subjects had been diagnosed with RA and treated with MTX between September 30, 1999, and October 1, 2009. Outcomes of interest were the amount of time on MTX monotherapy or multiple disease-modifying anti-rheumatic drug (DMARD) therapy before addition of additional DMARDs or biologic agents, respectively. We conducted Cox regressions and Kaplan-Meier curves for association between SC MTX use and length of time before therapeutic change. We conducted chi-square tests for association between SC MTX use and elevated liver function tests (LFT).

MTX monotherapy: SC MTX was associated with a significantly lower likelihood of therapeutic change (HR 0.64, 95% CI 0.52-0.78). Multiple DMARD therapy: SC MTX was not associated with a lower risk of adding a biologic (HR 1.13, 95% CI 0.97-1.31). Liver enzymes: There was no significant association between use of SC MTX and decreased frequency of abnormal LFTs [p=0.09 for alanine aminotransferase (ALT), p=0.924 for aspartate aminotransferase (AST)].

Use of SC MTX is associated with longer duration of MTX monotherapy before addition of other DMARDs/biologic agents in RA patients. Use of SC MTX is not associated with significantly longer duration of multiple DMARD therapy before addition of biologic agents. Use of oral MTX is not significantly associated with increased frequency of elevated LFTs.