SAT0047 Predicting maintenance of response based on disease characteristics and early clinical response in rheumatoid arthritis patients upon withdrawal of adalimumab
Authors: JS Smolen, P Emery, H Zhang, X Wang, J Suboticki, I Sainsbury, A Kavanaugh
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Some patients (pts) with rheumatoid arthritis (RA) achieve low disease activity (LDA) after treatment with adalimumab (ADA) plus methotrexate (MTX) and can maintain LDA after ADA withdrawal<sup>1</sup>. However, others experience a flare in disease activity. The factors associated with loss or maintenance of response are not understood. <h3>Objectives</h3> To identify pt disease characteristics and early clinical responses, which predict maintenance of LDA upon ADA withdrawal in individual RA pts. <h3>Methods</h3> Data from the OPTIMA trial were used in this <i>post hoc</i> analysis. In period 1 (P1), pts were treated for 26 weeks (wks) with ADA+MTX or placebo (PBO) +MTX. Pts on ADA+MTX who achieved DAS28-CRP &lt;3.2 at wks 22 and 26 (responders) were randomized to ADA withdrawal, or ADA+MTX continuation up to Wk 78. Responders to PBO+MTX in P1 continued on PBO+MTX up to Wk 78 (PBO continuation). Data from the ADA withdrawal arm were used to predict LDA at Wk 78 by DAS28-CRP (≤3.2) or SDAI (≤11). Potential factors including baseline (BL) disease characteristics and Wk 26 responses, including DAS28-CRP, SDAI, ACR score components, modified total sharp score (mTSS) and joint space narrowing score (JSN), were screened by the LASSO method<sup>2</sup>, which performs variable selection by penalizing unduly complicated models, with/without incorporating the speed of DAS28-CRP or SDAI response as an individual predictor. Logistic regression on the LASSO-selected factors yielded coefficients used to derive individual scoring equations and prediction scores for Wk 78 outcomes (fig footnote). Prediction score cutoffs were established by the regression tree method<sup>3</sup>. The results were validated in data from the PBO continuation arm. <h3>Results</h3> For the prediction of DAS28-CRP LDA at Wk 78, BL physician global assessment (PhGA) and health-assessment questionnaire-disability index (HAQ-DI), and Wk 26 DAS28-CRP, HAQ-DI, JSN and CRP were selected by LASSO, and used to calculate the prediction score. Including speed of response did not affect the predictors chosen. Out of 9 pts predicted not to have DAS28-CRP LDA at Wk 78, 0 had LDA (NPV=100%) (fig 1). Out of 66 pts predicted to have DAS28-CRP LDA at Wk 78, 63 predictions were correct (PPV=96.5%). Results were comparable for most cutoff categories in the validation arm (PPV=82%); however, no pts were predicted to have a non-response at Wk 78. For the prediction of SDAI LDA at Wk 78, the NPV was 86% (1/7 predictions incorrect); PPV was 95% (39/41 predictions correct); in the validation arm, the PPV was 82%. <h3>Conclusions</h3> DAS28-CRP LDA at 78 wks could be individually predicted for up to 63% pts in OPTIMA who withdrew ADA/continued PBO+MTX with 96.5% accuracy, based on demographics and clinical outcomes at 6 months. This instrument could help identify pts who may be able to maintain LDA upon ADA withdrawal. <h3>References</h3> Smolen et al, 2013. Lancet;383. Tibshirani, R, 1996. J Royal and Stat Society; 58. Breiman L., et al, 1984. Classification and Regression Trees. Wadsworth. <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 Grant/research support from: AbbVie, Consultant for: AbbVie, P. Emery Grant/research support from: from Pfizer, MSD, AbbVie Inc., BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly., Consultant for: from Pfizer, MSD, AbbVie Inc., BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly., H. Zhang Employee of: AbbVie, X. Wang Employee of: AbbVie, J. Suboticki Employee of: AbbVie, I. Sainsbury 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.