Background/Purpose:
Our previous analyses using the national administrative database from Veteran
Health Administration showed that RA patient who were switched from oral to subcutaneous
MTX due to intolerance or lack of response were more likely to stay on
methotrexate monotherapy longer. We seek to determine if RA patients who were
on multiple traditional DMARD stay longer on traditional DMARD when subcutaneous
MTX was used. We also compare the occurrences of liver enzymes abnormalities
between those on subcutaneous MTX with those on oral therapy.

Methods: The
duration of multiple traditional DMARD therapy, defined as the time between
starting the use of a multiple traditional DMARD regimen that includes
methotrexate and the switch to or addition of biologics, is compared between
those on oral methotrexate and those on subcutaneous methotrexate for at least
30 days using a Wilcoxon-Matt-Whitney test. 
Factors that could potentially influence the duration of multiple
traditional DMARD use include: gender, age, race, and maximum MTX dose. These
factors were assessed using a log-rank test and Kaplan-Meier curves; Cox
regression models were run to correct for patient variables. Liver enzyme
abnormalities were compared between patients on subcutaneous and oral MTX who received
MTX monotherapy for >30 days; abnormal alanine aminotransferase (ALT) levels
and aspartate aminotransferase (AST) levels were defined as exceeding twice the
upper limit of normal.

Results: Of the 13,254
patients who were treated with a DMARD for at least 90 days, 6541 were on more
than one DMARD at any point in time, and in 3586, MTX was included in the multiple
DMARD regimens. There were 1837 biologic starts among these 3586 patients (1604
were treated with oral MTX, 197 with subcutaneous MTX). Patient treated with
oral MTX remained on multiple traditional DMARD for a mean (SD) of 683 (650)
days compared with 580 (595) days for patients treated with subcutaneous MTX
(P=0.014). Based on log-rank tests (see figure), the use of subcutaneous MTX was
associated with significantly shorter duration of traditional multiple DMARD
therapy use (P=0.025). After adjustment for patient variables using Cox
regression models, the association of subcutaneous MTX use with the duration on
multiple traditional DMARD therapy was no longer significant (P=0.107). Age and
race remained significantly associated after corrections. Of the patients
treated with MTX who had ALT and/or AST levels assessed, the rates of abnormal
ALT and AST levels were not significantly different between those receiving
oral and subcutaneous MTX (P=0.090 and P=0.924, respectively).

Conclusion: Unlike
the duration of MTX monotherapy, the duration of multiple traditional DMARD use
was not significantly associated with use of subcutaneous MTX. Among those
using MTX for >30 days, there was no
significant differences in liver enzyme abnormalities between patients treated
with subcutaneous MTX and oral MTX.