Dr. Fleischmann has received consulting fees from Pfizer and Abbott (less than $10,000 each) and has received study grants from Pfizer and Abbott.
Version of Record online: 28 FEB 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 3, pages 617–629, March 2012
How to Cite
Fleischmann, R., Cutolo, M., Genovese, M. C., Lee, E. B., Kanik, K. S., Sadis, S., Connell, C. A., Gruben, D., Krishnaswami, S., Wallenstein, G., Wilkinson, B. E. and Zwillich, S. H. (2012), Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis & Rheumatism, 64: 617–629. doi: 10.1002/art.33383
Presented in part at the Annual European Congress of Rheumatology of the European League Against Rheumatism, Copenhagen, Denmark, June 2009 and at the 73rd Annual Scientific Meeting of the American College of Rheumatology, Philadelphia, PA, October 2009. Previously published in abstract form: Kanik K, Fleischmann R, Cutolo M, Genovese M, Lee EB, Sadis S, et al. Phase 2b dose ranging monotherapy study of the oral JAK inhibitor CPP-690,550 and adalimumab vs placebo in patients with active rheumatoid arthritis with an inadequate response to DMARDs [abstract]. Ann Rheum Dis 2009;68 Suppl 3:123; and Fleischmann R, Genovese MC, Gruben D, Kanik KS, Wallenstein GV, Wilkinson B, et al. Safety and efficacy after 24 week dosing of the oral JAK inhibitor CP-690,550 as monotherapy in patients with active rheumatoid arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10:1924.
ClinicalTrials.gov identifier: NCT00550446.
- Issue online: 28 FEB 2012
- Version of Record online: 28 FEB 2012
- Accepted manuscript online: 27 SEP 2011 10:18AM EST
- Manuscript Accepted: 22 SEP 2011
- Manuscript Received: 12 JUL 2010
To compare the efficacy, safety, and tolerability of 5 doses of oral tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response to disease-modifying antirheumatic drugs.
In this 24-week, double-blind, phase IIb study, patients with RA (n = 384) were randomized to receive placebo, tofacitinib at 1, 3, 5, 10, or 15 mg administered orally twice a day, or adalimumab at 40 mg injected subcutaneously every 2 weeks (total of 6 injections) followed by oral tofacitinib at 5 mg twice a day for 12 weeks. The primary end point was the responder rate according to the American College of Rheumatology 20% improvement criteria (ACR20) at week 12.
Treatment with tofacitinib at a dose of ≥3 mg twice a day resulted in a rapid response with significant efficacy when compared to placebo, as indicated by the primary end point (ACR20 response at week 12), achieved in 39.2% (3 mg; P ≤ 0.05), 59.2% (5 mg; P < 0.0001), 70.5% (10 mg; P < 0.0001), and 71.9% (15 mg; P < 0.0001) in the tofacitinib group and 35.9% of patients in the adalimumab group (P = 0.105), compared with 22.0% of patients receiving placebo. Improvements were sustained at week 24, according to the ACR20, ACR50, and ACR70 response rates as well as classifications of remission according to the 3-variable Disease Activity Score in 28 joints (DAS28) using C-reactive protein and the 4-variable DAS28 using the erythrocyte sedimentation rate. The most common treatment-emergent adverse events (AEs) in patients across all tofacitinib treatment arms (n = 272) were urinary tract infection (7.7%), diarrhea (4.8%), headache (4.8%), and bronchitis (4.8%).
Tofacitinib monotherapy at ≥3 mg twice a day was efficacious in the treatment of patients with active RA over 24 weeks and demonstrated a manageable safety profile.