Background In patients (pts) with rheumatoid arthritis (RA), the long-term impact of sustained versus (vs) transient clinical remission (REM) has not been assessed thoroughly, although REM duration has been shown to affect structural outcomes1. The relationship of different definitions of clinical remission (REM) with function and structural integrity has not been assessed.
Objectives To explore the importance of sustained REM or disease control for long-term outcomes, and assess various definitions of REM in adalimumab (ADA) long-term trials.
Methods Data are from 2 trials of ADA in early RA pts; In PREMIER, pts received ADA, methotrexate (MTX) or ADA+MTX for 2 years (yrs), after which they could enter an open label (OL) period for upto 8 yrs2. In OPTIMA, pts received ADA+MTX, or placebo (PBO) +MTX for 26 weeks (wks). Based on whether or not pts achieved DAS28-CRP <3.2 at wks 22 and 26, pts withdrew ADA, continued on PBO+MTX, ADA+MTX or OL ADA+MTX until Wk 783. For this analysis, non-sustained REM/disease control was defined as meeting one of the following at 6 months but not 1 yr: DAS28-CRP <2.6; simplified disease activity index (SDAI) ≤3.3; clinical disease activity index (CDAI) ≤2.8. Sustained REM/disease control was defined as meeting these criteria at both 6 months and 1 yr. The mean change from baseline in health assessment questionnaire- disability index (ΔHAQ-DI), or modified total Sharp score (ΔmTSS), and the number of pts without clinical worsening of HAQ-DI (Δ≤0.22) were assessed over 78 wks for OPTIMA, or 5 yrs for PREMIER. NRI and LOCF were used for binary and continuous variables, respectively.
Results In OPTIMA, by any of the REM criteria, pts in sustained REM had larger mean ΔHAQ-DI over time (Fig 1A) vs pts in non-sustained REM. Pts with non-sustained DAS28-CRP <2.6 vs non-sustained CDAI REM had numerically smaller ΔHAQ-DI up to Wk 52. Over time, more pts in sustained vs non-sustained REM using DAS28-CRP<2.6 (but not CDAI or SDAI criteria) did not have clinical worsening of HAQ-DI, possibly due to more suppression of inflammatory components upon achieving CDAI REM but not DAS28-CRP <2.6 in these early RA pts (Fig 1B). At Wk 78, ΔmTSS at Wk 78 was smaller for pts in sustained vs non-sustained DAS28-CRP <2.6, and similar for sustained and non-sustained CDAI REM (Fig 1C). Somewhat fewer pts at Wk 78 may have contributed to some variability. Trends were similar in PREMIER (not shown).
Conclusions Pts who were in sustained disease control/REM had better clinical, functional and radiographic outcomes over the long- term, vs pts in a more transient state, regardless of the REM criteria used, although for CDAI REM, functional and radiographic outcomes were similar for sustained and non-sustained REM, in line with its higher stringency.
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Acknowledgements AbbVie: study sponsor, contributed to design, data collection, analysis, interpretation; and writing, reviewing, approval of final version. Medical writing: Naina Barretto, of AbbVie.
Disclosure of Interest J. Smolen: None declared, C. Gabay Grant/research support from: AbbVie Inc, Amgen, BMS, MSD, Pfizer, Roche, Celgene, Sanofi, and Regeneron., Consultant for: AbbVie Inc, Amgen, BMS, MSD, Pfizer, Roche, Celgene, Sanofi, and Regeneron., D. Aletaha Grant/research support from: AbbVie Inc., Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche., Consultant for: AbbVie Inc., Pfizer, Grünenthal, Merck, Medac, UCB, Mitsubishi/Tanabe, Janssen, and Roche., P. Emery Grant/research support from: research grants and consulting fees from Pfizer, MSD, AbbVie Inc., Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly., Consultant for: research grants and consulting fees from Pfizer, MSD, AbbVie Inc., Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly., I. Sainsbury Employee of: AbbVie, Y. Zhang Employee of: AbbVie, A. Kavanaugh Grant/research support from: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB., Consultant for: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB.