Relationship between different clinical measurements and patient-reported outcomes: Results from a phase 3 study of tofacitinib or methotrexate in methotrexate-naïve patients with rheumatoid arthritis

Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives: Here we compare the relationship between clinical measures and patient-reported outcomes (PROs) in patients (pts) with RA treated with tofacitinib or methotrexate (MTX). Methods: MTX-naïve pts with RA from a double-blind, parallel group, Phase 3 trial (ORAL Start; NCT01039688) were randomised (2:2:1) and treated with tofacitinib 5 mg twice daily (BID) monotherapy (N=373), tofacitinib 10 mg BID monotherapy (N=397) or MTX titrated from 10 to 20 mg/week (N=186). Clinical measures included: the proportion of pts achieving ACR50 and ACR70 responses, the proportion achieving low disease activity (LDA) measured by Clinical Disease Activity Index (CDAI LDA, CDAI≤10) and Simplified Disease Activity Index (SDAI LDA, SDAI≤11), and the proportion achieving remission (REM) measured by CDAI REM (CDAI≤2.8) and SDAI REM (SDAI≤3.3). PROs included: proportion of pts achieving improvements in physical function measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI, to normative values <0.5). Results: At Month 6, a greater proportion of pts achieved ACR responses, LDA and REM with tofacitinib 5 mg or 10 mg BID than with MTX (Table 1). Most pts who achieved LDA and REM by one measure also achieved LDA and REM by other measures (Table 1); however, discordance was observed between different measures of LDA and REM, and appeared greater with MTX vs either tofacitinib dose (Table 1). As expected there was a high degree of concordance between Overall, pts achieving LDA or ACR50 showed less improvement from baseline in patient-reported pain, and patient global assessment of disease compared with tender joints, swollen joints, physician global assessment of disease and

HAQ-DI:

pts receiving MTX showed an overall lower improvement in these PROs compared with tofacitinib 5 mg or 10 mg BID. In general, better improvements and consistency in PROs were observed in ACR50 responders compared with measures of LDA. Pts achieving ACR70, CDAI REM and SDAI REM showed similar improvements across PROs and similarly between MTX and tofacitinib. Conclusions: A higher proportion of MTX-naïve pts receiving tofacitinib 5 or 10 mg BID achieved a clinical response compared with pts receiving MTX. While most pts achieve similar responses across different clinical measures, many may achieve a response in one measure but not the other. Variability of responses with clinical measures should be considered when setting treat-to-target goals in pts with RA.