Objective: The objective of this study was to compare the effectiveness of a combination of TNFα inhibitors with either methotrexate (MTX) or leflunomide (LEF) in the treatment of patients with rheumatoid arthritis in a real-world setting.
Methods: Data from 1,769 outpatients enrolled in the German biologics register RABBIT who were treated with one of the TNFα inhibitors adalimumab (ADA), etanercept (ETA), or infliximab (INF) in combination with either MTX (n= 1,375) or LEF (n=394) were included in the analysis. Clinical status including disease activity as well as treatment data were documented by the treating rheumatologist at baseline and at 3, 6, 12, 18, 24, 30, and 36 months of follow-up.
Results: Patients treated with a combination of biologics with LEF had significantly higher baseline disease activity than those treated with MTX. The highest disease activity was found for patients treated with the combination INF/LEF. After 36 months, the discontinuation rates were 46.3%, 51.3% and 61.5% for combinations of ETA, ADA and INF with MTX and 53.4%, 63.1% and 67.1% for combinations with LEF, respectively. EULAR response rates after 24 months ranged from 74% to 81% for combinations with MTX and 72% to 81% for combinations with LEF.
Conclusion: The current clinical practice is to use MTX as a first choice for the combination with TNFα antagonists. However, in a number of patients MTX has to be replaced by another DMARD. Our data support the view that LEF is a useful alternative if MTX is contraindicated.