Guidelines
support the use of combination conventional synthetic Disease-Modifying Antirheumatic
Drugs (csDMARDs), switching csDMARDs and/or use of
biologic DMARDs (bDMARDs) treatment in active rheumatoid arthritis (RA) after
use of methotrexate (MTX).

The purpose of
this study was to determine treatment practices after use of MTX in patients
with RA who were on either monotherapy or combination csDMARDs in a large
observational cohort (OBRI) in order to determine contemporary practice where
use of bDMARDs from government coverage is restricted to active RA (+RF and/or
+ACPA) or erosions, SJC≥5 with MTX failure, combination failure
(triple csDMARDs:  MTX + hydroxychloroquine + sulfasalazine) or use of
leflunomide. Methods: Patients enrolled
in the Ontario Best Practices Research Initiative (OBRI) with documented MTX failure defined as discontinuation due to
side effect, primary / secondary failure, or patient / physician decision were included. Demographics and disease
parameters at MTX failure were compared between monotherapy failures, double
therapy (Rx) failures, and triple Rx failures.   Results:   A
total of 313 patients with MTX failure were included with a mean (SD) age of 58.8
(13.2) years and disease duration of 6.7 (8.2) years. Of these, 102 (32.6%)
were on MTX monotherapy, 156 (49.8%) were on double (MTX +1 csDMARD) Rx, and 55
(17.6%) were on triple or more (MTX + multiple csDMARDs) Rx, respectively, at
the time of MTX failure. At the time of MTX failure disease duration was
significantly higher in patients failing monotherapy and double Rx as compared
to triple Rx (7.5 vs. 6.8 vs. 4.5 years, respectively; P=0.003). Figure 1 shows
the disposition of patients who transitioned to csDMARD monotherapy, csDMARD
combination Rx or bDMARDs treatment. Patients receiving monotherapy were more
apt to have switches to other monotherapy whereas those on combination Rx 
received more combination csDMARDs and bDMARDs combination Rx.   Conclusion:   There
are inherent differences in the selection of subsequent treatment regimen
between patients failing MTX monotherapy vs. MTX combination therapy. Overall,
the results of the current analysis suggest the use of a sequential treatment intensification
strategy in routine clinical practice in Ontario.   Figure 1:  Treatment
Profile after MTX Failure by Type of MTX Failure