Background: Sarilumab is a human interleukin (IL)-6 receptor inhibitor approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). The relationship between disease activity (DA), sarilumab treatment, and improvements in patient-reported outcomes (PROs) has not been well-studied. Objectives: Assess the association between DA and PROs in three sarilumab Phase 3 trials. Methods: This post hoc analysis included patients from three trials: two placebo-controlled trials (MOBILITY; NCT01061736 and TARGET; NCT01709578) with sarilumab dose groups 150 mg and 200 mg q2w that were combined for this analysis; and MONARCH (NCT02332590) with sarilumab 200 mg versus adalimumab 40 mg q2w. Associations between PROs and DA were tested at Week 24. All statistics are descriptive. Results: Sarilumab was generally associated with larger PRO improvement than placebo both in patients who did and patients who did not achieve DA thresholds (Table). Improvement was less pronounced in patients who did not achieve DA thresholds. In the active-comparator trial, PROs improved in both treatment groups, across all DA levels. There was no clear difference between sarilumab and adalimumab in PRO response. There was a consistent trend of positive but reduced PRO responses with increased DA level using multiple cut-points (data not shown). Conclusion: Achieving lower DA was associated with increased PRO improvements. In patients who did not achieve DA thresholds, the improvements were more favorable with sarilumab than placebo. This may support the emerging concept that mechanisms other than inflammation may contribute to improvements in PROs, potentially mediated via IL-6 signaling. Acknowledgments: Study funding and medical writing support (Matt Lewis, Adelphi Communications Ltd) were provided by Sanofi and Regeneron Pharmaceuticals, Inc. Disclosure of Interests: Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Gerd Rudiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Hubert van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, Amy Praestgaard Employee of: Sanofi Genzyme, Gregory St John Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB