A study of the combination of Etanercept and Anakinra in patients treated unsuccessfully with Mtx showed no added benefit but an increase in serious infection (0% in Etanercept and 3.7-7.4% for combination therapy), injection site reaction, and neutropenia.[18] In comparison with the TNF inhibitors, IL-1 inhibitors have had a smaller impact on rheumatic disease. The gene discussed is TNF; the disease is infection.