Abstract THU0192 –Table 1.

Conclusion: Among MTX-naïve patients with active RA, treatment withUPA 15 mg or 30 mg daily for 12 weeks resulted in statistically signifi-cant and clinically meaningful improvements in physical function, pain,fatigue, AM stiffness, HRQoL, and work productivity compared with MTX.The NNTs to achieve these improvements were favourable.

REFERENCE:[1] van Vollenhoven R, et al. Arthritis Rheumatol. 2018;70(S9):983, abstract

891.

Acknowledgement: Financial support for the study was provided by AbbVie.AbbVie participated in the interpretation of data, review, and approval of theabstract. All authors contributed to the development of the publication and main-tained control over the final content. Medical writing services were provided byJoann Hettasch of JK Associates Inc., a member of the Fishawack Group of Com-panies, and funded by AbbVie.Disclosure of Interests: Vibeke Strand Consultant for: AbbVie, Amgen,Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Cre-scendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen,Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz,Sanofi, Servier, UCB., Namita Tundia Shareholder of: AbbVie, Employeeof: AbbVie, Sebastiao Radominski Consultant for: Abbvie, Celgene, Gen-entech/Roche, Janssen, Pfizer, UCB, Speakers bureau: Abbvie, Celgene,Genentech/Roche, Janssen, Pfizer, UCB, Alan Friedman Shareholder of:AbbVie, Employee of: AbbVie, Kendall Dunlap Shareholder of: AbbVie,Employee of: AbbVie, Deborah Goldschmidt Employee of: Analysis GroupInc, which received consulting fees from AbbVie for this study., MartinBergman Shareholder of: Johnson and Johnson (parent company of Jans-sen), Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech/Roche,Janssen, Merck, Novartis, Pfizer, and Sanofi/Regeneron, Speakers bureau:AbbVie, Amgen, BMS, Celgene, Genentech/Roche, Janssen, Merck,Novartis, Pfizer, and Sanofi/RegeneronDOI: 10.1136/annrheumdis-2019-eular.978

THU0193 EFFICACY OF TOFACITINIB MONOTHERAPY,TOFACITINIB WITH METHOTREXATE ANDADALIMUMAB WITH METHOTREXATE IN PATIENTSWITH EARLY (£2 YEARS) VS ESTABLISHED (>2 YEARS)RHEUMATOID ARTHRITIS: A POST HOC ANALYSIS OFDATA FROM ORAL STRATEGY

Tsutomu Takeuchi1, Yoshiya Tanaka2, Naonobu Sugiyama3, Noriko Iikuni4,Koshika Soma5, Harry Shi6, Eduardo Mysler7, Robert J Moots8, Josef S. Smolen9,Roy Fleischmann10. 1Keio University School of Medicine, Tokyo, Japan;2University of Occupational and Environmental Health, Kitakyushu, Japan; 3PfizerJapan Inc, Tokyo, Japan; 4Pfizer Inc, New York, NY, United States of America;5Pfizer Inc, Groton, CT, United States of America; 6Pfizer Inc, Collegeville, PA,United States of America; 7Organización Médica de Investigación, Buenos Aires,Argentina; 8Institute of Ageing and Chronic Disease, University of Liverpool,Liverpool, United Kingdom; 9Medical University of Vienna, Vienna, Austria;10Metroplex Clinical Research Center and University of Texas SouthwesternMedical Center, Dallas, TX, United States of America

Background: Tofacitinib is an oral JAK inhibitor for the treatment of RA.Greater improvements in efficacy outcomes have been reported with tofa-citinib 5 mg BID ± csDMARDs in patients (pts) with early vs establishedRA.1,2

Objectives: This post hoc analysis of ORAL Strategy data evaluated theefficacy and safety of tofacitinib monotherapy, tofacitinib + methotrexate(MTX) and adalimumab (ADA) + MTX, stratified by baseline (BL) RAduration.Methods: ORAL Strategy (NCT02187055) was a P3b/4, 1-yr, double–blind,triple-dummy, active comparator-controlled study. MTX inadequate-res-ponder pts were randomised 1:1:1 to receive tofacitinib 5 mg BID (tofamono), tofacitinib 5 mg BID + MTX (tofa+MTX), or ADA SC 40 mg Q2W+ MTX (ADA+MTX); MTX was dosed at 15–25 mg/wk except in casesof intolerance/toxicity. In this analysis, pts were stratified by BL RA dura-tion as having early (£2 yrs) or established (>2 yrs) RA. Efficacy out-comes (Months [M]3, 6 and 12): ACR20/50/70; change from BL (Δ) inDAS28–4(ESR), SDAI and CDAI; and rates of DAS28-4(ESR)-, SDAI-and CDAI–defined LDA (£3.2, £11 and £10, respectively) and remission(<2.6, £3.3 and £2.8, respectively). Nominal p values for treatment com-parisons were calculated without multiplicity adjustment; p<0.05 was con-sidered significant. Treatment-emergent AEs and serious AEs (SAEs)were assessed throughout the study.

Abstract THU0193 – Figure 1

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Results: 241 pts had early RA (tofa mono: N=80; tofa+MTX: N=83; ADA+MTX: N=78; mean RA duration: 1.0–1.1 yrs); 905 pts had establishedRA (tofa mono: N=304; tofa+MTX: N=293; ADA+MTX: N=308; mean RAduration: 9.4–10.4 yrs). BL demographics and disease characteristics weregenerally comparable for early vs established RA pts, with someexpected differences (the latter were slightly older, and a greater propor-tion had received prior bDMARDs); RF+ and anti-CCP+ rates were higherfor established RA pts (Table). ACR50 and ΔDAS28-4(ESR) were gener-ally similar for tofa mono and tofa+MTX up to M12 in early RA but sig-nificantly greater with tofa+MTX in established RA (p<0.05); ADA+MTXwas not statistically different vs tofa+MTX in early RA (Figure). Trendswere similar for all outcomes. AE rates were generally similar in early vsestablished RA. Trends for SAEs were less clear; rates were lowest fortofa+MTX in early RA and slightly higher for both tofacitinib arms vsADA+MTX in established RA (Table).Conclusion: Efficacy was similar for tofa mono and tofa+MTX in earlyRA, and significantly higher with tofa+MTX in established RA. ADA+MTXwas numerically but not always significantly more effective than tofacitinibin early RA. AE rates were generally similar regardless of BL RA dura-tion. These findings, especially in established RA, are consistent with theconclusion of the primary analysis.3 Limitations to this post hoc analysisinclude low numbers of early RA pts.

REFERENCES:[1] Hall S, et al. Arthritis Rheum 2016; 68(S10): 1999-2001.[2] Fleischmann RM, et al. RMD Open 2016; 2: e000262.[3] Fleischmann RM, et al. Lancet 2017; 390: 457-468.

Acknowledgement: Study sponsored by Pfizer Inc. Medical writing support wasprovided by Christina Viegelmann of CMCConnect and funded by Pfizer Inc.Disclosure of Interests: Tsutomu Takeuchi Grant/research support from:Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi SankyoCo., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, AsahikaseiPharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., EisaiCo., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd.,Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei,Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi San-kyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku,Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, ChugaiPharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer JapanInc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.,Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., TaishoToyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., JanssenPharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCBJapan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., NovartisPharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, NipponkayakuCo.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Phar-maceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho ToyamaPharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd.,Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bris-tol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen,Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho,Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., EliLilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co.,Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., BristolMyers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: AstellasPharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mit-subishi Tanabe Pharma Co., Pfizer Japan Inc., Santen PharmaceuticalCo., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVieGK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd.,SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc.,Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, AsahiKasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daii-chi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, NipponKayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin,Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai PharmaceuticalCo. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., AstellasPharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., TeijinPharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K.,Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD,Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei,Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai,Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc,Sanofi, Takeda, UCB, YL Biologics, Naonobu Sugiyama Shareholder of:Pfizer Inc, Employee of: Pfizer Inc, Noriko Iikuni Shareholder of: PfizerInc, Employee of: Pfizer Inc, Koshika Soma Shareholder of: Pfizer Inc,

Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employeeof: Pfizer Inc, Eduardo Mysler Grant/research support from: AbbVie, Bris-tol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Grant/research sup-port from: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune,Pfizer Inc, and Roche, Consultant for: AbbVie, Bristol-Myers Squibb, EliLily, Janssen, Medimmune, Pfizer Inc, and Roche, Speakers bureau: Abb-Vie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Speakersbureau: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune,Pfizer Inc, and Roche, Robert J Moots Grant/research support from: Bio-gen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz,and UCB, Consultant for: Biogen, Bristol-Myers Squibb, Chugai, Novartis,Pfizer Inc, Roche, Sandoz, and UCB, Speakers bureau: Biogen, Bristol-Myers Squibb, Chugai, Novartis, Pfizer Inc, Roche, Sandoz, and UCB,Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen,MSD, Pfizer Inc, Roche, Consultant for: AbbVie, Amgen, AstraZeneca,Astro, Celgene, Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medi-mmune, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi,UCB, Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Celgene,Celtrion, Eli Lilly, GlaxoSmithKline, ILTOO, Janssen, Medimmune, MSD,Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB, Roy Fleisch-mann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, PfizerInc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca,Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis,Pfizer Inc, Sanofi-Aventis, UCBDOI: 10.1136/annrheumdis-2019-eular.587

THU0194 SELECTIVE INHIBITION OF JANUS KINASE 1 (JAK1) BYFILGOTINIB MODULATES THE DISEASE-ASSOCIATEDWHOLE BLOOD TRANSCRIPTIONAL PROFILE OFPATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

Peter C. Taylor1, Bryan Downie2, Luting Zhuo2, Rachael E. Hawtin2, Jinfeng Liu2,Amer M. Mirza2. 1Botnar Research Centre, University of Oxford, Oxford, UnitedKingdom; 2Gilead Sciences, Inc., Foster City, United States of America

Background: Filgotinib (FIL), an oral selective JAK1 inhibitor, was safeand efficacious in FINCH2, a randomized, double-blind, placebo-controlled,phase 3 study in patients with active rheumatoid arthritis (RA) who hadan inadequate response to biologic disease-modifying anti-rheumatic drugs(bDMARDs).1 The whole blood transcriptional profile of patients wasevaluated.Objectives: Identify RA-associated gene transcripts and biological path-ways that are altered in response to FIL treatment and interrogate FIL-modulated biomarkers correlated with disease activity.Methods: RA patients enrolled in FINCH2 (n=449) were randomized 1:1:1and received FIL (100 mg, 200 mg) or placebo (PBO) once daily plus astable background dose of methotrexate. Whole blood samples fromenrolled patients were collected at baseline (BL) and weeks 4 and 12 forRNA sequencing. Spearman’s rank correlation of BL disease activity(DAS28[CRP]) was calculated to define disease-associated genes (DAGs)and pathways (DAPs). Differential expression of 5155 genes and FIL-spe-cific changes were determined after subtracting gene expression changesin the PBO group. Biological pathways (910 total) were analyzed byGene Set Enrichment Analysis (GSEA) or single-sample GSEA. A false-discovery rate of 5% was applied for all analyses.Results: At weeks 4 and 12, more genes were significantly differentiallyexpressed in the FIL 200 mg arm vs the 100 mg arm; and, consistentwith increased clinical efficacy, the average magnitude of change in geneexpression was larger. No single gene reached a threshold of signifi-cance for differential expression in PBO-treated patients. FIL treatmentinduced a stronger reversal of DAG expression (rho range: –0.35 to –0.59) compared to PBO (rho ∼ –0.3) at weeks 4 and 12. DAGs mostprominently reversed by FIL included FAM20A and METTL7B. Top-rankedpathways associated positively with disease activity at BL included inflam-matory response, complement activity, and cell cycle. Hallmark pathwaysmost significantly reduced following FIL treatment included IL-6/JAK/STAT,inflammatory, and interferon response, consistent with observed effects ofFIL in preclinical models and phase 2 DARWIN studies. In contrast, IL-6/JAK/STAT signaling increased at weeks 4 and 12 with PBO. DAPsshowed a similar reversal of gene expression (rho range: –0.43 to –0.58)with FIL at weeks 4 and 12 compared to PBO (rho range: –0.007 to –0.024) suggesting that FIL treatment may attenuate RA-mediated IL-6/JAK/STAT signaling, inflammation, and other RA-associated pathways cor-related with clinical outcome measures.Conclusion: The whole blood transcriptional profile of patients followingFIL treatment showed a dose-dependent reduction in the expression of

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