Background/Purpose: Patients (pts) with rheumatoid arthritis (RA) who achieve disease control in response to treatment with a tumor necrosis factor inhibitor (TNFi) may lose that response permanently under continuous treatment (1). We examined whether pts with early RA, in sustained clinical remission (REM) or low disease activity (LDA) lose their state of clinical response during continuous treatment with originator adalimumab (ADA) and/or methotrexate (MTX).

Methods: This post hoc analysis used data from PREMIER, a 2-year trial in early RA pts who were TNFi- and MTX-naïve. Pts received ADA, MTX, or ADA+MTX. Responders were defined as pts who sustained one of the following states at both Weeks (Wk) 20 and 24: 28-joint disease activity state based on C-reactive protein (DAS28-CRP) <2.6 or <3.2 (LDA); simplified disease activity index (SDAI) SDAI ≤3.3 (SDAI REM) or ≤11 (SDAI LDA), clinical disease activity index (CDAI) ≤ 2.8 (CDAI REM) or ≤10 (CDAI LDA) or ACR-EULAR Boolean REM.  A loss of response was defined as loss of DAS28-CRP LDA for all remaining visits (up to Wk 104 or premature discontinuation) starting after Wk 24 (with ≥2 consecutive visits of LDA loss). The percentage of pts who lost DAS28-CRP LDA response in each treatment arm, and mean CDAI values, were calculated at each visit.

Results: Overall, for each response category, few pts permanently lost their DAS28-CRP LDA state after Wk 24 through Wk 104 (Table 1). Pts on ADA+MTX lost DAS28-CRP LDA less often, although the number of pts was small to begin with in some response categories in the monotherapy groups. For pts in DAS28-CRP LDA through Wk 104, the mean CDAI scores (shown at Wks 24, 26 and 104 in Table 1) ranged from 0.8-5, and these pts also remained in CDAI LDA at those time points. Pts in stringent REM (SDAI, CDAI or Boolean) at Wk 20 and 24 had lower mean CDAI scores than pts with DAS28-CRP <2.6 or LDA. Further, they maintained that response and a low CDAI value throughout the subsequent period, while pts with DAS28-CRP<2.6 experienced an increase of DAS28-CRP above that threshold on the group level. The CDAI score of pts who lost their DAS28-CRP LDA state rose at the visit at which the first loss was recorded (Fig 1).

Conclusion: A majority of TNFi- and MTX-naïve pts with early RA in sustained REM or LDA after 20-24 wks of treatment maintained a low disease state through the period assessed. The loss of response was an infrequent phenomenon. References:

1.    Finckh et al, Ann Rheum Dis, 2006;65:646-52