BIOLOGIC FREE DISEASE CONTROL (BFDC) IN EARLY RA: PREDICTORS OF SUCCESSFUL WITHDRAWAL OF ADALIMUMAB (ADA) AFTER ACHIEVING STABLE LOW DISEASE ACTIVITY WITH ADA PLUS METHOTREXATE (MTX) – DATA FROM THE OPTIMA STUDY

Background: It is unknown which pts may be able to achieve BFDC after initially responding to combination therapy with ADA plus MTX. Objectives: To identify variables predictive of 1) stable DAS28(CRP)<3.2 (low disease activity, LDA) following 26 wks of treatment with either MTX monotherapy or ADA+MTX, and 2) BFDC following ADA withdrawal. Methods: MTX-naïve pts ≥18 yrs with RA <1 yr, active disease [DAS28>3.2, and ESR≥28 mm/hr or CRP≥1.5 mg/dL], and either >1 erosion, RF+, or anti-CCP+ were randomized to ADA+MTX or placebo (PBO)+MTX for 26 wks. Pts who achieved stable DAS28<3.2 at wks 22 & 26 with ADA+MTX were re-randomized to blindly withdraw or continue ADA for an additional 52 wks. This post hoc analysis examined variables associated with DAS28<3.2 at wks 22 & 26 and with BFDC (DAS28<3.2 at wks 52, 66, & 78). Continuous variables included CRP, SJC66, and Pt and MD global assessments (GA) of disease activity at baseline (BL) and wks 12 or 26. Categorical variables included sex, smoker, BL concomitant steroid use, joint erosions, MTP erosions, HLA-DRB1 shared epitope, IL4R, and FcγRIIb, and wk 12 or 26 clinical responders. Step-wise multivariate selection was done on variables with P<.10 in univariate analysis. Results: At wks 22 & 26, 44% (207/466) ADA+MTX and 24% (112/460) MTX pts achieved stable DAS28<3.2 (P<.001). Lower disease activity levels at wk 12 were modestly associated with reaching the stable LDA target (table). Significantly more pts who achieved this target and continued ADA+MTX maintained stable DAS28<3.2 from wk 52-78 (71/82, 87%) compared with pts who withdrew ADA (49/75, 65%; P=.002). Significant predictors of successful BFDC in pts who withdrew ADA included MD GA at BL and CRP levels at wk 26 (table). Table 1. Odds ratios (95% Confidence Intervals) and P values for Predicting Stable DAS28<3.2 Target and Long-term BFDC by Multivariate Logistic Regression Explanatory VariableStable Target at Wk 22 & 26Stable Target at Wk 52, 66, & 78 PBO+MTXADA+MTXADA+MTX[R]→PBO+MTX BL MDGA0.99 (0.97, 1.00)n.i.0.92 (0.87, 0.97) P=0.04P=0.002 Joint erosions at BL (no vs. yes)n.i.n.i.0.19 (0.03, 1.20) P=0.08 Wk 12 SJC660.84 (0.79, 0.90)0.88 (0.84, 0.93)0.81 (0.65, 1.01) P<0.001P<0.001P=0.06 Wk 12 PtGA0.97 (0.95, 0.98)0.95 (0.94, 0.96)n.i. P<0.001P<0.001n.i. Wk 12 CRPn.i.0.97 (0.94, 1.00)n.i. P=0.03 Wk 26 CRP (Tertiles: 1 [0-2 mg/L] vs 3 [>4 mg/L])n.i.n.i.45.1 (6.19, 328.5) P=0.007 [R], responder for DAS28 <3.2 at wks 22 & 26; n.i., not included in model. Conclusions: Lower disease activity levels early during treatment were predictive of achieving an initial stable DAS28<3.2 target. Significantly more pts who continued ADA+MTX maintained this target compared with pts who had ADA withdrawn. The physician's assessment of disease activity may identify pts as candidates for BFDC, and low CRP levels after achieving the initial target are indicative of increased likelihood of success upon ADA withdrawal. Disclosure of Interest: J. Smolen Grant/Research support from: Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, BMS, Celgene Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz, UCB, P. Emery Consultant for: Pfizer Inc, Merck, Abbott, Roche, BMS, UCB, R. Fleischmann Consultant for: Abbott, R. van Vollenhoven Grant/Research support from: Abbott, Glaxo Smithkline, Merck, Pfizer, Roche, UCB Pharma, Consultant for: Abbott, Glaxo Smithkline, Merck, Pfizer, Roche, UCB Pharma, S. Florentinus Shareholder of: Abbott, Employee of: Abbott, S. Santra Shareholder of: Abbott, Employee of: Abbott, H. Kupper Shareholder of: Abbott, Employee of: Abbott, A. Kavanaugh Grant/Research support from: Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Consultant for: Abbott, Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCBCitation: Annals of the Rheumatic Diseases, volume 71, supplement 3, year 2012, page 516Session: Rheumatoid arthritis – anti-TNF therapy (Poster Presentations )