AB0291 Identification of joint locations that are poor prognostic indicators and require more intensive therapy in an early, rapidly progressing ra cohort: a post hoc agree analysis. (12th June 2018) - Durez, P.
Abstract : Background: Patients (pts) with early RA often present with multiple areas of involvement. Limited data exist to identify which specific joints or joint locations may be indicative of poorer prognosis and require more intensive initial therapy. 1 Objectives: This analysis investigated which joint locations have the poorest prognosis and compared clinical response rates between abatacept (ABA)+MTX and MTX monotherapy by baseline (BL) swollen joint status for specific joint locations. Methods: Data from AGREE (NCT00122382 ), a double-blind Phase III study of ABA+MTX (n=256) vs MTX (n=253) in biologic-naïve pts with early (≤2 years [yrs]) erosive RA, were analysed by BL swollen joint status (present, absent) for 8 different joint locations: hands, wrists, elbows, shoulders, jaw, knees, ankles and feet. Overall characteristics and study results were reported previously. 2 Swelling was evaluated at BL and after 6 months (mths) of treatment. Differences between treatment groups in clinical response endpoints (i.e. DAS28 [CRP]<2.6, SDAI≤3.3, CDAI≤2.8, Boolean and HAQ remission ≤0.5 at 6 mths) and swelling resolution at 6 mths were assessed by BL swollen joint status, for each joint location. Results: In an early RA cohort of pts at risk of active, rapidly progressing disease, the proportions of pts (n=509) with a swollen joint at BL were 99% hand, 92% wrist, 79% ankle, 69% knee, 66% foot, 48% elbow, 34% shoulder and 9% jaw. Pts with a swollen jaw (n=45) had more tender joints (mean [SD] 40.0 [15.1] vs 30.1 [14.1]), more swollen joints (35.9 [13.3] vs 21.1 [9.5]), higher total Sharp score (9.4 [10.1] vs 6.9 [9.1]) and longer disease duration (11.7 [9.2] yrs vs 6.0 [6.9] yrs) than those without jaw swelling (n=464). Higher HAQ-DI was seen in pts with a swollen knee or shoulder (1.8 [0.6] vs 1.5 [0.7] and 1.9 [0.6] vs 1.6 [0.7], respectively). Presence of BL synovitis was not associated with greater BL anti-citrullinated protein antibodies or RF positivity, probably due to the inclusion of mainly seropositive pts. In general, absence of BL swelling was associated with higher clinical response at 6 mths, both for ABA+MTX and MTX. Independent of BL swollen joint status, ABA+MTX had higher clinical response rates (DAS28, SDAI, CDAI, Boolean and HAQ remission) than MTX, except for the non-swollen wrist. Overall mean Boolean remission rates were 13.7% for ABA+MTX vs 5.5% for MTX with difference in proportions (95% CI) of 8.1% (2.6, 13.7) (p=0.003). The largest difference in Boolean remission rate (95% CI) favouring ABA+MTX was 9.6% (4.2, 15.1) (p<0.001) in pts with a swollen wrist at BL (figure 1). Difference in swollen joint resolution between ABA+MTX and MTX was most pronounced for pts with a swollen hand (mean [95% CI]: 42.7% [36.7, 48.8] vs 27.9% [22.4, 33.4], respectively). Conclusions: BL swelling in the shoulder, knee and jaw is associated with a more severe RA profile. Remission rates were higher with ABA+MTX than MTX when BL swelling was present, especially in the wrist. Also, swollen joint resolution was more pronounced with ABA+MTX, especially in the hands. References: [1] Bergstra SA, et al. RMD Open2017;3:e000568. [2] Westhovens R, et al. Ann Rheum Dis2009;68:1870–7. Disclosure of Interest: P. Durez Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Sanofi, S. Robert Employee of: Bristol-Myers Squibb, A. Thiry Employee of: Bristol-Myers Squibb, H. Ahmad Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb