SAT0142 Predictors of inadequate response and rapid radiographic progression in patients with early rheumatoid arthritis receiving methotrexate: a post hoc analysis of 2 randomized, controlled trials of adalimumab

Background Methotrexate (MTX) is recommended as first-line therapy in patients (pts) with rheumatoid arthritis (RA). 1 However, information is limited regarding factors that may predict a poor response to MTX. Objectives To identify predictors of MTX insufficient response (IR) and rapid radiographic progression (RRP) among pts with early RA receiving 6 months (mos) of MTX therapy. Methods In OPTIMA, pts with RA 1.5 from baseline (BL) to 6 mos. In pts with available data, backward logistic regression was used to identify potential predictors of MTX-IR and RRP. Candidate predictors included BL demographics, time-averaged disease parameters for 3 time intervals (through 4 wks, 8 wks, and 12 wks of MTX exposure), and BL disease characteristics for the 12-wk interval. Time-averaged variables were calculated as area under the curve standardized for length of time interval. Results This analysis included 525 MTX-IR and 162 MTX responders. Mean disease duration at BL was 6 mo for both groups. The mean Disease Activity Score 28 (C-reactive protein; DAS28[CRP]) was 6.2 vs 5.6, Health Assessment Questionnaire Disability Index (HAQ-DI) was 1.6 vs 1.3, and mTSS was 15.5 vs 12.2 for MTX-IR vs MTX responders, respectively. 171 pts experienced RRP, while 499 pts had no RRP; the mean disease duration at BL was 6 mo for both groups. The mean DAS28(CRP) was 6.4 vs 6.0 and HAQ-DI was 1.6 vs 1.5 for pts experiencing RRP vs pts who did not experience RRP, respectively. Mean mTSS at BL was higher for pts who experienced RRP (20.7) vs those who did not (12.4). Predictors of MTX-IR and RRP at 6 mos are shown in the Figure. Time-averaged HAQ-DI and DAS28(CRP) through 12 wks were the strongest predictors of both MTX-IR and RRP. Additionally, early clinical response (time-averaged DAS28[CRP]) at both 4 and 8 wks was predictive of both MTX-IR and RRP; however, time-averaged HAQ-DI was not predictive until wk 12. Conclusions In the OPTIMA and PREMIER trials, post-BL measures of RA activity appeared to be the strongest predictors of subsequent MTX-IR and of RRP. Pts who are likely to progress on MTX or have RRP may be good candidates for switching to earlier step-up therapy to reduce the likelihood of permanent bone damage. References Singh JA, et al. Arthritis Care Res (Hoboken). 2016;68(1):1–25. Acknowledgements AbbVie: study sponsor, contributed to design, data collection, analysis, interpretation; and (funded) writing, reviewing, approval of final version. Medical writing: Y.E. Yarker, M.J. Theisen, Complete Publication Solutions, LLC. Disclosure of Interest A. Kavanaugh Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Consultant for: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, R. F. van Vollenhoven Grant/research support from: AbbVie, Amgen, BMS, GSK, Pfizer, Roche, and UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Centocor-Janssen, Lilly, Merck, Pfizer, Roche, UCB, and Vertex, B. A. Wolfe Shareholder of: AbbVie, Employee of: AbbVie, S. Florentinus Shareholder of: AbbVie, Employee of: AbbVie, S. Chen Shareholder of: AbbVie, Employee of: AbbVie, J. L. Suboticki Shareholder of: AbbVie, Employee of: AbbVie, J. S. Smolen Grant/research support from: AbbVie, Consultant for: AbbVie, Speakers bureau: AbbVie