Methotrexate (MTX), sulfasalazine (SSZ) and leflunomide (LEF) are recommended treatments for PsA patients with active peripheral arthritis. In the publication of a recent negative placebo-controlled randomised trial of MTX in PsA, it was suggested that the sequencing of conventional DMARDs before biologics should be re-evaluated¹. Our objective was to assess the pattern of conventional DMARD use, and to compare the effectiveness of MTX, SSZ and LEF in a longitudinal observational study (LOS) of patients with PsA.

Methods:

Data were extracted from NOR-DMARD, a LOS of arthritis patients starting a new DMARD treatment, with follow-up at 3, 6, 12 months and then yearly. Patients diagnosed with PsA and starting treatment with MTX, SSZ or LEF were identified. We studied baseline characteristics and 3- and 6-month treatment responses overall, and performed statistical comparisons between treatments. For the statistical comparisons we selected the first inclusion of those patients included sequentially with several DMARDs so that only individual patients were included. Unadjusted comparisons were done by ANOVA, Kruskall-Wallis or Chi² test, as appropriate, and analyses with adjustment for important baseline differences were performed by ANCOVA and logistic regression analysis. Swollen and tender joint counts included the standard 28 joints for RA and ankles and forefeet bilaterally (32-SJC and 32-TJC, respectively).

Results:

 A total of 1351 prescriptions of MTX (n=1000), SSZ (n=212) and LEF (n=139) in 1212 individual patients were identified – 128 patients were registered with >=2 of the drugs and 11 patients with all 3 drugs. Among MTX/SSZ/LEF patients 71% vs. 61% vs. 6.5% were DMARD na•ve, respectively, and 47% of patients on LEF had failed both MTX and SSZ. Patients treated with LEF also had longer disease duration. Mean baseline DAS28 for MTX/SSZ/LEF was 4.2/4.0/4.3, respectively. The baseline characteristics across groups for the first inclusion per patient (MTX n=949, SSZ n=177, LEF n=86) were very similar (baseline DAS28 4.2/3.9/4.3 for MTX/SSZ/LEF, respectively). Selected 3- and 6-month outcomes are shown in the Table. Responses were numerically similar for the overall group of patients (n=1351). Two-year drug survival was superior for MTX (0.71) vs. SSZ (0.40; HR 1.96; p<0.001) and LEF (0.29; HR 2.47, p<0.001), with no significant difference between SSZ and LEF. Reasons for discontinuation were inefficacy and intolerance in roughly the same frequency (40-50%) for both SSZ and LEF. Mean dose of MTX was 15.1 mg at 6 months; for SSZ 88% used >=2000 mg daily and for LEF 86% used 20 mg daily at 6 months.

Table. 3- and 6-month responses (individual patients)

Conclusion:

MTX was the most commonly used first-line DMARD while LEF was rarely used as a first-line DMARD. Effectiveness was modest and generally similar, but MTX performed better for some measures, including drug survival.

1.      Kingsley G et al, Rheumatology 2012;51:1368-77.