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

Abstract

Objective: Our study aims to determine whether the use of subcutaneous methotrexate (SC MTX) isassociated with prolonged MTX use and lower incidence of hepatotoxicity in rheumatoid arthritis(RA) patients on MTX monotherapy and multiple drug therapy.Methods: We conducted a retrospective cohort study using national databases of a large hospital sys-tem. Subjects had been diagnosed with RA and treated with MTX between September 30, 1999, andOctober 1, 2009. Outcomes of interest were the amount of time on MTX monotherapy or multipledisease-modifying anti-rheumatic drug (DMARD) therapy before addition of additional DMARDs orbiologic agents, respectively. We conducted Cox regressions and Kaplan-Meier curves for associationbetween SC MTX use and length of time before therapeutic change. We conducted chi-square testsfor association between SC MTX use and elevated liver function tests (LFT).Results: MTX monotherapy: SC MTX was associated with a significantly lower likelihood of therapeu-tic change (HR 0.64, 95% CI 0.52-0.78). Multiple DMARD therapy: SC MTX was not associated with alower risk of adding a biologic (HR 1.13, 95% CI 0.97-1.31). Liver enzymes: There was no significantassociation between use of SC MTX and decreased frequency of abnormal LFTs [p=0.09 for alanineaminotransferase (ALT), p=0.924 for aspartate aminotransferase (AST)].Conclusion: Use of SC MTX is associated with longer duration of MTX monotherapy before additionof other DMARDs/biologic agents in RA patients. Use of SC MTX is not associated with significantlylonger duration of multiple DMARD therapy before addition of biologic agents. Use of oral MTX is notsignificantly associated with increased frequency of elevated LFTs.