SAT0122 Efficacy of addition, or continuation, of adalimumab in patients who did not achieve stable low disease activity with methotrexate or adalimumab plus methotrexate in the optima study:
Authors: A. Kavanaugh, R. Fleischmann, P. Emery, R. van Vollenhoven, S. Florentinus, J.W. Shaw, S. Santra, H. Kupper, L. Redden, J. Smolen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Guidelines for rheumatoid arthritis (RA) recommend adjusting treatment every 3-6 months to the desired state of disease activity. Patients (pts) treated with adalimumab (ADA) plus methotrexate (MTX) may have delayed responses without major radiographic consequences<sup>1</sup>. <h3>Objectives</h3> To determine outcomes after introduction of ADA in pts who did not achieve a stable low disease activity (LDA) target with MTX alone compared with pts continuing ADA+MTX who did not achieve the target. <h3>Methods</h3> MTX-naïve pts ≥18 yrs with RA &lt;1 yr, active disease [DAS28(CRP)&gt;3.2, ESR≥28 mm/hr or CRP≥1.5 mg/dL], and &gt;1 erosion, RF+, or anti-CCP+ were randomized to ADA+MTX or placebo (PBO)+MTX for 26 wks. Pts who did not achieve a stable LDA target (DAS28&lt;3.2 at wks 22 &amp; 26) were offered open-label ADA+MTX for 52 wks. Categorical responses were analyzed using non-responder imputation and radiographic outcomes by multiple imputation. Predictors of rapid radiographic progression (RRP, ΔmTSS&gt;1.5 in 26 wks) were assessed. <h3>Results</h3> Among pts who completed 26 wks, 76% (348/460) PBO+MTX and 56% (259/466) ADA+MTX did not achieve the stable LDA target (inadequate response [IR]). Introduction of ADA enhanced responses among PBO+MTX[IR] pts. Improvements were also observed among ADA+MTX[IR] pts who continued ADA+MTX despite no adjustment of concomitant medications (Table). Significantly more damage occurred in PBO+MTX[IR] pts: mean ΔmTSS from wk 0-26 was 1.2 compared with 0.3 for ADA+MTX[IR] (<i>P</i>&lt;.001). RRP occurred in 18% PBO+MTX[IR] pts, compared with 5% ADA+MTX[IR] pts. Baseline erosions were a strong predictor of RRP. Addition of ADA halted radiographic progression in PBO+MTX[IR] pts: mean ΔmTSS from wk 0-78 was 1.3; radiographic inhibition was sustained in ADA+MTX[IR] pts: mean ΔmTSS from wk 0-78 was 0.4. <h3>Conclusions</h3> Introduction of ADA to pts who failed to achieve a stable LDA target with MTX alone decreased disease activity and halted radiographic progression; however, pts with baseline erosions may be candidates for earlier treatment intensification. Continued ADA+MTX treatment yielded ongoing improvements with little radiographic progression, demonstrating the disconnect between control of disease activity and inhibition of damage with ADA. <h3>References</h3> Keystone et al. ACR 2011 P1102 <h3>Disclosure of Interest</h3> 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 UCB, R. Fleischmann Consultant for: Abbott, P. Emery Consultant for: Pfizer Inc, Merck, Abbott, Roche, BMS, UCB, 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, J. Shaw Shareholder of: Abbott, Employee of: Abbott, S. Santra Shareholder of: Abbott, Employee of: Abbott, H. Kupper Shareholder of: Abbott, Employee of: Abbott, L. Redden Shareholder of: Abbott, Employee of: Abbott, 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