The ORAL Scan study met all primary endpoints at the 10 mg BID dose, showing statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates at six months; in reducing the progression of structural damage, as measured by change from baseline in modified Total Sharp Score (mTSS) at six months; in improving physical function, as measured by mean change in HAQ DI at three months; and in reaching DAS28-4(ESR) <2.6 at six months.
For the 5 mg BID dose, the study demonstrated statistically significant improvements versus placebo in ACR20 response rates at six months, but the difference from placebo in mTSS did not reach statistical significance at six months. Due to the pre-specified step-down statistical procedure, no further testing was performed on HAQ DI and DAS28-4(ESR) <2.6 for the 5 mg BID dose.
No new safety signals emerged in the ORAL Scan study. The efficacy and safety profile of tofacitinib in this study remains consistent with that seen previously in the clinical program. A full analysis of the ORAL Scan efficacy and safety data will be submitted to a future scientific meeting.
About ORAL Scan
ORAL Scan is an ongoing two-year study that randomized 800 patients with moderate-to-severe active RA who had an inadequate response to MTX to receive tofacitinib 5 or 10 mg BID or placebo added to background MTX. At the three month visit, non-responding placebo-assigned patients were advanced in a blinded fashion to a predetermined treatment of tofacitinib, 5 or 10 mg BID, for the remainder of the study. At the end of six months, all placebo-assigned patients were advanced to their predetermined tofacitinib treatment assignment in a blinded fashion for the remainder of the study. The two year data from this study are expected in 2012.
About Rheumatoid Arthritis
Rheumatoid arthritis is a chronic inflammatory autoimmune disease that typically affects the hands and feet, although any joint lined by a synovial membrane may be affected. RA affects approximately 1.3 million people in the U.S.(1) and one percent of the adult population worldwide.(2)
Tofacitinib is a novel, oral Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for RA. More than 4,000 RA patients have been treated with tofacitinib in clinical trials to date. Unlike current therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, tofacitinib takes a novel approach, targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network.
In addition to ORAL Scan (A3921044), the ORAL Trials clinical program includes the following pivotal Phase 3 studies of tofacitinib in RA:
- ORAL Solo (A3921045): 6-month study in inadequate responders to a disease modifying anti-rheumatic drug (DMARD), traditional or biologic, receiving tofacitinib monotherapy, evaluating signs and symptoms and physical function.
- ORAL Sync (A3921046): 12-month study in inadequate responders to a DMARD (traditional or biologic) receiving tofacitinib and background traditional DMARD(s), evaluating signs and symptoms and physical function.
- ORAL Standard (A3921064): 12-month study in inadequate responders to MTX receiving tofacitinib and background MTX, with active comparator of adalimumab and background MTX, evaluating signs and symptoms and physical function.
- ORAL Step (A3921032): 6-month study in inadequate responders to TNF-inhibiting therapy receiving tofacitinib and background MTX, evaluating signs and symptoms and physical function.
In addition, there is an ongoing Phase 3 study that will not be a part of the initial registration:
- ORAL Start (A3921069): 24-month study in MTX-naïve patients receiving tofacitinib monotherapy or MTX, including a structural endpoint in addition to evaluating signs and symptoms and physical function.
Pfizer is also studying orally administered tofacitinib in psoriasis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and renal transplant, and topical tofacitinib in both psoriasis and dry eye disease.
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1. Arthritis Today. “What is Rheumatoid Arthritis.” Accessed 24 February 2011. Available at: http://www.arthritistoday.org/conditions/rheumatoid-arthritis/all-about-ra/what-is-ra.php.
2. Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res Ther. 2009; 11(Suppl 1): S1.Published online 2009 April 6. doi: 10.1186/ar2662.