A 2-Year Phase 3 Study Of CP-690,550 In Patients With Active Rheumatoid Arthritis On Background Methotrexate

• Drug: CP-690,550
  
  Oral tablets administered at 5 mg BID daily for 6 months (nonresponders advance to second intervention at 3 months) during the double-blind, placebo-controlled period.
  Other Name: Double-blind, placebo-controlled period
• Drug: CP-690,550
  
  Oral tablets administered at 5 mg BID daily through the end of the study during the double-blind, active-extension period.
  Other Name: Double-blind, Active Extension Period
• Drug: CP-690,550
  
  Oral tablets administered at 10 mg BID daily for 6 months (nonresponders advance to second intervention at 3 months) during the double-blind, placebo-controlled period.
  Other Name: Double-blind, placebo-controlled period
• Drug: CP-690,550
  
  Oral tablets administered at 10 mg BID daily through the end of the study during the double-blind, active-extension period.
  Other Name: Double-blind, Active Extension Period
• Drug: Placebo
  
  Oral placebo tablets administered BID daily for 6 months (nonresponders advance to second intervention at 3 months) during the double-blind, placebo-controlled period.
  Other Name: Double-blind, placebo-controlled period
• Drug: Placebo
  
  Oral placebo tablets administered BID daily for 6 months (nonresponders advance to second intervention at 3 months) during the double-blind, placebo-controlled period.
  Other Name: Double-blind, Active Extension Period
• Drug: CP-690,550
  
  Oral tablets administered at 10 mg BID daily through the end of the study during the double-blind, active-extension period.
  Other Name: Double-blind, placebo-controlled period

• Experimental: Sequence 1
  
  Interventions:
  

  • Drug: CP-690,550
  • Drug: CP-690,550
• Experimental: Sequence 2
  
  Interventions:
  

  • Drug: CP-690,550
  • Drug: CP-690,550
• Placebo Comparator: Sequence 3
  
  Interventions:
  

  • Drug: Placebo
  • Drug: CP-690,550
• Placebo Comparator: Sequence 4
  
  Interventions:
  

  • Drug: Placebo
  • Drug: CP-690,550

• van der Heijde D, Strand V, Tanaka Y, Keystone E, Kremer J, Zerbini CAF, Cardiel MH, Cohen S, Nash P, Song YW, Tegzová D, Gruben D, Wallenstein G, Connell CA, Fleischmann R; ORAL Scan Investigators. Tofacitinib in Combination With Methotrexate in Patients With Rheumatoid Arthritis: Clinical Efficacy, Radiographic, and Safety Outcomes From a Twenty-Four-Month, Phase III Study. Arthritis Rheumatol. 2019 Jun;71(6):878-891. doi: 10.1002/art.40803. Epub 2019 Apr 24.
• Kivitz AJ, Cohen S, Keystone E, van Vollenhoven RF, Haraoui B, Kaine J, Fan H, Connell CA, Bananis E, Takiya L, Fleischmann R. A pooled analysis of the safety of tofacitinib as monotherapy or in combination with background conventional synthetic disease-modifying antirheumatic drugs in a Phase 3 rheumatoid arthritis population. Semin Arthritis Rheum. 2018 Dec;48(3):406-415. doi: 10.1016/j.semarthrit.2018.07.006. Epub 2018 Jul 19.
• Hall S, Nash P, Rischmueller M, Bossingham D, Bird P, Cook N, Witcombe D, Soma K, Kwok K, Thirunavukkarasu K. Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Australian Rheumatoid Arthritis Population. Rheumatol Ther. 2018 Dec;5(2):383-401. doi: 10.1007/s40744-018-0118-2. Epub 2018 Jun 11.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
• Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14. Erratum in: Ann Rheum Dis. 2017 Mar;76(3):611.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.
• van der Heijde D, Tanaka Y, Fleischmann R, Keystone E, Kremer J, Zerbini C, Cardiel MH, Cohen S, Nash P, Song YW, Tegzová D, Wyman BT, Gruben D, Benda B, Wallenstein G, Krishnaswami S, Zwillich SH, Bradley JD, Connell CA; ORAL Scan Investigators. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: twelve-month data from a twenty-four-month phase III randomized radiographic study. Arthritis Rheum. 2013 Mar;65(3):559-70. doi: 10.1002/art.37816.

Inclusion Criteria:

• Adults with moderate to severe rheumatoid arthritis on a stable dose of methotrexate

Exclusion Criteria:

• Pregnancy, severe acute or chronic medical conditions, including serious infections or clinically significant laboratory abnormalities.