[THU0151] EFFECTS OF TOFACITINIB (CP-690,550), AN ORAL JANUS KINASE INHIBITOR, OR ADALIMUMAB ON PATIENT REPORTED OUTCOMES IN A PHASE 3 STUDY OF ACTIVE RHEUMATOID ARTHRITIS
R.F. van Vollenhoven1, G. Wallenstein2, E.B. Lee3, R. Fleischmann4, S.H. Zwillich2, D. Gruben2, T. Koncz5, J. Bradley2, B. Wilkinson2, V. Strand6. 1Karolinska Institute, Stockholm, Sweden; 2Pfizer Inc, Connecticut, United States; 3Seoul National University, Seoul, Republic of Korea; 4Metroplex Clinical Research Center, Dallas, Texas; 5Pfizer Inc, New York; 6Stanford University, Palo Alto, California, United States
Background: Tofacitinib (CP-690,550) is a novel, oral Janus kinase (JAK) inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis (RA).
Objectives: To compare the effects of tofacitinib 5 and 10 mg twice daily (BID), and active control adalimumab, with placebo (PBO) on patient reported outcomes (PROs) in patients (pts) with active RA and an inadequate response to methotrexate (MTX).
Methods: Pts in this 12-month (Mo), phase 3, randomised control trial (RCT) with RA (≥6 TJC/SJC; ESR >28 mm/h or CRP >7 mg/L) and prior MTX failure were randomised (4:4:4:1:1) to 5 treatment sequences: tofacitinib 5 mg or 10 mg BID; adalimumab 40 mg subcutaneous (SC) injections once every two weeks (Q2W); PBO advanced to tofacitinib 5 mg BID; and PBO advanced to tofacitinib 10 mg BID, all with MTX. Pts on PBO with <20% improvement in TJC and SJC after 3 months were blindly advanced to tofacitinib 5 or 10 mg BID at that time, and all other PBO pts after 6 months. We analysed changes from Baseline to Mo 6 based on the Full Analysis Set (all pts who received ≥1 dose of study drug) using a mixed-effect longitudinal model for the following PROs (secondary endpoints): PtGA [VAS]; pain (VAS); physical function (HAQ-DI); HR-QoL (SF-36); fatigue (FACIT-F), and sleep (MOS Sleep Scale).
Results: At Mo 6, treatment with tofacitinib 5 and 10 mg BID, and adalimumab 40 mg Q2W, resulted in statistically significant improvements from baseline vs placebo in all PROs (see Table):
|% of pts reporting improvements ≥MCIDb||n=46||5 mg BID||10 mg BID||40 mg Q2W|
|% pts reporting ≥MCID [-10]||62.37||70.11||72.38||70.56|
|% pts reporting ≥MCID [-10]||64.52||72.41||74.59||69.27|
|Physical function (HAQ-DI)||-0.33||-0.66***||-0.68***||-0.57**|
|% pts reporting ≥MCID [-22]||56.99||71.84*||77.35**||74.44*|
|left" colspan="5"]HR-QoL (SF-36)|
|Physical Component Score||4.72||8.52**||8.81***||7.25*|
|% pts reporting ≥MCID [2.5]||72.04||68.21||70.00||71.51|
|Mental Component Score||0.89||5.51**||6.00***||3.93*|
|% pts reporting ≥MCID [2.5]||30.11||58.38***||59.44***||51.96**|
|% pts reporting ≥MCID ||45.65||57.23||67.40**||55.56|
|Sleep (MOS Sleep Scale; overall sleep)||-4.14||-12.47**||-12.13**||-10.26*|