Title: Physician and patient characteristics associated with the decision to treat rheumatoid arthritis patients with biologic monotherapy in usual care settings

Authors: Mariely Nieves-Plaza1, Heather Eng2, Ilinca Metes3, Ashwini Shewede4, Stephen R. Wisniewski2, Ani John4 and Marc C. Levesque3

Affiliations: University of Pittsburgh Clinical and Translational Science Institute1, School of Public Health2 and School of Medicine3, Pittsburgh, PA, USA and Genentech Inc., South San Francisco, CA4

Background/Purpose: Approximately 30% of rheumatoid arthritis (RA) patients treated with a biologic, receive the biologic as monotherapy i.e. without concomitant oral disease modifying anti-rheumatic drugs (DMARDs). The purpose of this study was to compare the characteristics of RA subjects treated with biologic monotherapy versus RA subjects treated with biologic therapy combined with oral DMARDs (combo therapy).

Methods: We used data from a longitudinal registry (Rheumatoid Arthritis Comparative Effectiveness Research (RACER)) based at the University of Pittsburgh that includes 1,029 RA subjects with 5,886 usual care clinic visits. We compared the demographic, disease activity, physician and prior treatment characteristics of RA subjects who initiated a biologic therapy since RACER’s inception (n = 473 subjects with 602 biologic initiations). Using variables with p < 0.05 in bivariate analyses, we developed a multivariable random-intercept logistic regression model that accounted for between subject correlations.

Results: Among 602 biologic initiations from Feb 2010 to May 2013, 31.2% of biologic therapy was monotherapy. Individual physicians (n = 19) varied widely with a range of prescribed monotherapy from 10% to 55%. In bivariate analyses, monotherapy compared to combo therapy was associated with longer disease duration (16.4 vs. 13.3 years, p=0.04), higher alanine aminotransferase (ALT) (29.4 vs. 25.5 U/L, p = 0.02), aspartate aminotransferase (AST) (27.1 vs. 22.7 U/L, p = 0.02) and alkaline phosphatase (ALP) (85.8 vs. 79.0 U/L, p < 0.01), and lower physician visual analogue scale (VAS) scores of global health (2.9 vs. 3.5, p = 0.02). As expected, no immediate prior therapy (p = 0.003) and previous use of monotherapy (p = 0.001) were associated with monotherapy use, whereas previous use of combo therapy was associated with lower use of monotherapy (p = 0.05). In multivariable analyses, after adjustment for AST and ALT levels and disease duration, the odds of monotherapy treatment increased 6% per unit increase in ALP level (OR [95% CI]; 1.06 [1.01, 1.11]) and decreased 40% per unit increase in physician VAS (0.60 [0.40, 0.89]).

Conclusions: Liver enzyme elevations and the physician’s global health VAS were the strongest predictors of monotherapy use. The presence of liver disease is typically a contraindication to the use of methotrexate and leflunomide and this likely explains the liver enzyme association. Although liver enzyme elevations were associated with use of biologic monotherapy, other comorbidities, as measured by Charlson scores, were not associated with biologic monotherapy use. Surprisingly, our analysis did not find associations of biologic monotherapy use with composite disease activity measures (DAS28, CDAI and RAPID3) or their individual components, except for the physician’s global health VAS; worse physician global health assessments were associated with more use of combo therapy. Coupled with the wide variation in physician monotherapy prescribing habits, this suggests that besides liver enzyme elevations, physician characteristics may strongly influence use of biologic monotherapy and will be the focus of future analyses.