MedicalResearch: What are the main findings of the study?
Dr. Wilkinson: ORAL Start showed that XELJANZ (tofacitinib citrate) 5 and 10 mg twice daily (BID), taken by itself without methotrexate (MX), inhibited the progression of structural damage and reduced the signs and symptoms of rheumatoid arthritis (RA), and was statistically significantly superior to methotrexate on these measures at Month 6 (primary endpoint) and at all measured time points up to 24 months in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate. XELJANZ is not indicated in patients who had not previously received methotrexate.
- Both doses of XELJANZ met the study’s co-primary efficacy endpoints of mean change from baseline in van der Heijde modified Total Sharp Score (mtss) [0.18 and 0.04 (both P<0.001) for tofacitinib 5 and 10 mg BID, respectively, versus 0.84 for MTX], and ACR70 response rates [25.5% and 37.7% for tofacitinib 5 and 10 mg BID (both P<0.001) versus 12.0% for MTX], at Month 6.
- These results were sustained at all measured time points up to 24 months.
MedicalResearch: Were any of the findings unexpected?
Dr. Wilkinson: This was the first time that tofacitinib was compared directly head to head with methotrexate and the results indicated that tofacitinib was superior to methotrexate for the efficacy measures of inhibition of radiographic progression and signs and symptoms for Rheumatoid Arthritis (RA) in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate; while these results were not necessarily unexpected they were important in that they provide confirmation that there is another effective oral therapy for moderate to severe rheumatoid arthritis patients that have had an inadequate response to MTX. There were no unexpected or new safety signals seen in this study.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Wilkinson: This Phase 3 study in patients with moderately to severely active rheumatoid arthritis (RA) who had not previously received methotrexate (MTX) or therapeutic doses of MTX met its primary endpoints. This study showed that XELJANZ taken by itself was statistically significantly superior to MTX in measures of clinical, radiographic and functional efficacy Rheumatoid Arthritis outcomes, and these results were measured at 6 months as the primary endpoint and sustained over two years. This is important since some people don’t adequately respond, eventually stop responding, or have intolerance to MTX.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Wilkinson: Future studies of the comparison on methotrexate in other populations as well as continuing pharmacovigilance will provide additional information on the risk:benefit profile of this therapy.
Eun Bong Lee, M.D., Roy Fleischmann, M.D., Stephen Hall, M.D., Bethanie Wilkinson, Ph.D., John D. Bradley, M.D., David Gruben, Ph.D., Tamas Koncz, M.D., Sriram Krishnaswami, Ph.D., Gene V. Wallenstein, Ph.D., Chuanbo Zang, Ph.D., Samuel H. Zwillich, M.D., and Ronald F. van Vollenhoven, M.D. for the ORAL Start Investigators