Objectives Clinical trials of anti-TNF therapies have shown that concurrent methotrexate (MTX) therapy enhances the efficacy of TNF inhibitors. A scarcity of data exists on the benefits of combination therapy with IFX and MTX vs. leflunomide (LEF) in a real-world setting; therefore the BioTRAC Registry database was used to explore this question.

Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with IFX or golimumab as first biologics or after having been treated with a biologic for <6 months. RA patients treated with IFX who were enrolled between 2002-2014 were included in this analysis. Treatment durability was assessed with the Kaplan Meier (KM) estimator of the survival function and Cox regression.

Results 723 RA patients were included; at baseline 516 (71.4%) were on IFX+MTX, 115 (15.9%) on IFX+LEF, and 92 (12.7%) on IFX+MTX+LEF. The mean (SD) age was 55.5 (13.6) years, 76.2% were female and mean (SD) disease duration was 8.7 (9.2) years. The majority of patients were from Ontario (50.6%), followed by Western Canada (25.8%), and Quebec (20.9%). There were 217 (30.0%) patients who discontinued due to lack/loss of response, disease progression, adverse event (AE) or change in therapy with a KM-based mean (SE) time to discontinuation of 83.9 (3.0) months. Upon adjusting for potential confounders, higher durability was observed for the IFX+MTX group vs. IFX+LEF [hazard ratio -HR- (95% CI): 0.50 (0.25-1.01), P=0.055]. Moreover, factors independently associated with premature treatment termination were earlier enrolment period [HR2006-09 vs. 2002-05 (95% CI): 0.15 (0.02-1.15, P=0.068; HR2010-2014 vs. 2002-05 (95% CI): 0.09 (0.01-0.70), P=0.021], shorter baseline disease duration [HR (95% CI): 0.97 (0.93-1.00), P=0.054], and increased baseline pain levels [HR (95% CI): 1.14 (1.03-1.26), P=0.013]. 2,016 AEs were reported by 343 patients (106.8 events/100 patient-years) and 156 SAEs by 96 patients (8.3 events/100 patient-years). The incidence density ratio (IDR) (95% CI) was higher in the groups IFX+MTX vs. IFX+LEF for both AEs and SAEs with 1.44 (1.25-1.67) and 1.60 (0.94-2.73), respectively, however the latter was not statistically significant. When examining the triple combination therapy (IFX+MTX+LEF), higher durability was observed compared to both IFX+MTX [HR (95% CI): 3.68 (1.14-11.92); P=0.030] and IFX+LEF [HR (95% CI): 6.34 (1.72-23.34); P=0.006].

Conclusions The results of this real-world observational study have shown that combination therapy with IFX+MTX is associated with significantly higher treatment durability compared to IFX+LEF in RA patients with increased risk for AEs but not for SAEs.

Disclosure of Interest R. Faraawi Consultant for: Janssen, Speakers bureau: Janssen, R. Joshi: None declared, W. Bensen Consultant for: Janssen, D. Choquette Consultant for: AbbVie, Amgen, Celgene, BMS Canada, Janssen, Pfizer, W. Olszynski: None declared, R. Arendse Consultant for: Janssen, M. Sheriff: None declared, P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer, Roche, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, E. Rampakakis Employee of: JSS Medical Research, C. Tkaczyk Employee of: Janssen, F. Nantel: None declared