2627 - Tofacitinib (CP-690,550) in Combination with Traditional Disease-Modifying Anti-Rheumatic Drugs: Phase 3 Study Patient-Reported Outcomes in Patients with Active Rheumatoid Arthritis and An Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs

Wednesday, November 9, 2011: 11:00 AM
W196b (McCormick Place West)
V. Strand1, J. M. Kremer2, Z. G. Li3, S. Hall4, Roy M. Fleischmann5, M. C. Genovese6, E. Martin-Mola7, J. Isaacs8, D. Gruben9, G. Wallenstein9, S. Krishnaswami9, S. H. Zwillich9, T. Koncz10, R. Riese9, J. D. Bradley9 and the ORAL Sync investigators11, 1Stanford University, Palo Alto, CA, 2Albany Medical College and The Center for Rheumatology, Albany, NY, 3Peking University People's Hospital, Peking, China, 4Melbourne Rheumatology, Melbourne, Australia, 5MCRC, University of Texas, Dallas, TX, 6Stanford University Medical Center, Palo Alto, CA, 7Hospital Universitario La Paz, Madrid, Spain, 8University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom, 9Pfizer Inc., Groton, CT, 10Pfizer Inc., New York, NY, 11Groton
Presentation Number: 2627

Background/Purpose: Tofacitinib (CP-690,550) is a novel, oral Janus kinase (JAK) inhibitor investigated as a targeted immunomodulator for treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib vs placebo (PBO) were evaluated in pts with active RA with an inadequate response to ≥1 DMARD (traditional or biologic). Primary efficacy analyses have previously been reported. Here we report patient‑reported outcomes (PRO).

Methods: In this 12-month (Mo) study (NCT00856544), pts receiving traditional background DMARDs were randomized (4:4:1:1) to: tofacitinib 5 mg twice daily (BID); 10 mg BID; PBO advanced to 5 mg BID; and PBO advanced to 10 mg BID. At Mo 3 all ‘non-responder' PBO pts (<20% reduction from baseline in swollen/tender joint counts) were advanced to tofacitinib 5 or 10 mg BID. At Mo 6 all remaining PBO pts were advanced to tofacitinib. Most PROs were secondary endpoints and included: patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI); health-related quality of life (Medical Outcomes Survey [MOS] Short Form 36 [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and sleep (MOS Sleep Scale).

Results: 792 pts were treated; mean disease duration 8.1 - 10.2 years (y); mean age 50.8 - 53.3 y. At Mo 3 improvements from baseline in all PROs were statistically significantly greater in tofacitinib 5 and 10 mg BID groups than PBO (Table). Based on pts reporting improvements ≥ minimally clinically important differences [MCID], numbers needed to treat (NNTs) at Mo 3 for tofacitinib 5 and 10 mg BID, respectively, ranged from 4.6 - 6.0 and 3.7 - 8.3, respectively (full analysis set [FAS], no imputation).

Conclusions: In this Phase 3 study of tofacitinib in combination with traditional DMARDs, treatment with 5 and 10 mg BID resulted in consistent statistically significant and clinically meaningful improvements in multiple PROs vs PBO at Mo 3.



Keywords: DMARDs, Janus kinase (JAK), clinical trials, rheumatoid arthritis (RA) and rheumatoid arthritis, treatment

Disclosure: V. Strand, Amgen, AstraZeneca, BMS, Genentech, GlaxoSmithKline, Human Genome Sciences, Idera, Lilly, MedImmune, Merck Serono, NovoNordisk, Ono, Pfizer, Rigel, Roche, Sanofi-Aventis, Schering Plough, UCB, 5 ; J. M. Kremer, Pfizer Inc, 2, Pfizer Inc, 5 ; Z. G. Li, Pfizer Inc, 5 ; S. Hall, Pfizer Inc, 5 ; R. M. Fleischmann, Pfizer Inc, 2, Pfizer Inc, 5 ; M. C. Genovese, Pfizer Inc., 2, Pfizer Inc., 5 ; E. Martin-Mola, Pfizer Inc, 9 ; J. Isaacs, Pfizer Inc., 5 ; D. Gruben, Pfizer Inc, 3 ; G. Wallenstein, Pfizer Inc, 3, Pfizer Inc, 1 ; S. Krishnaswami, Pfizer Inc, 3 ; S. H. Zwillich, Pfizer Inc, 3, Pfizer Inc, 1 ; T. Koncz, Pfizer Inc, 3 ; R. Riese, Pfizer Inc, 3 ; J. D. Bradley, Pfizer Inc, 3 .