THU0110 The importance of sustained remission for longterm outcomes in patients with rheumatoid arthritis
Authors: J Smolen, C Gabay, D Aletaha, P Emery, I Sainsbury, Y Zhang, A Kavanaugh
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> 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 outcomes<sup>1</sup>. The relationship of different definitions of clinical remission (REM) with function and structural integrity has not been assessed. <h3>Objectives</h3> 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. <h3>Methods</h3> 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 yrs<sup>2</sup>. In OPTIMA, pts received ADA+MTX, or placebo (PBO) +MTX for 26 weeks (wks). Based on whether or not pts achieved DAS28-CRP &lt;3.2 at wks 22 and 26, pts withdrew ADA, continued on PBO+MTX, ADA+MTX or OL ADA+MTX until Wk 78<sup>3</sup>. 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 &lt;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. <h3>Results</h3> 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 &lt;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&lt;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 &lt;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 &lt;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). <h3>Conclusions</h3> 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. <h3>References</h3> Aletaha et al, Arthritis &amp; Rheum. 2009;5:1242. Breedveld et al. 2006. Arthritis &amp; Rheum;54:26. Smolen et al. 2014. Lancet;383:321. <h3>Acknowledgements</h3> AbbVie: study sponsor, contributed to design, data collection, analysis, interpretation; and writing, reviewing, approval of final version. Medical writing: Naina Barretto, of AbbVie. <h3>Disclosure of Interest</h3> 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.