In a previous 12-week, ascending-dose, randomized, placebo-controlled Trial 4 (http://ClinicalTrials.gov number, NCT00326339) involving 189 patients who had active RA despite methotrexate therapy, a significant reduction in arthritis activity and in serum levels of interleukin-6 and matrix metalloproteinase 3 were seen in the two groups that received the highest doses of R788 (100 mg twice daily and 150 mg twice daily), as compared with the groups that received placebo or the 50-mg dose of R788 twice daily. Here, IL6 is linked to arthritic joint disease.