THU0188 INHIBITION OF STRUCTURAL JOINT DAMAGE WITH UPADACITINIB AS MONOTHERAPY OR IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: 1 YEAR OUTCOMES FROM THE SELECT PHASE 3 PROGRAM
Authors: Charles Peterfy, Mark C. Genovese, In-Ho Song, Alan Friedman, Stephen Hall, Eduardo Mysler, Patrick Durez, Xenofon Baraliakos, Jose Jeffrey Enejosa, Tim Shaw, LI Yihan, Su Chen, Vibeke Strand
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Long–term prevention of structural joint damage is a key treatment goal in the management of RA<sup>1</sup>. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)–naïve RA patients (pts)<sup>2</sup> and in combination with MTX in pts with inadequate response (IR) to MTX<sup>3</sup>. <h3>Objectives</h3> To evaluate the progression of structural joint damage (radiographic) through Week 48 in pts with moderately to severely active RA treated with UPA monotherapy or in combination with MTX. <h3>Methods</h3> Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs), as previously described<sup>2,3</sup>. MTX–naïve pts were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT–EARLY, N=945], while MTX-IR pts were randomized to UPA 15mg QD or adalimumab (ADA) 40 mg eow or placebo (PBO), with continuous background MTX [SELECT–COMPARE, N=1629]. Both RCTs specifically enrolled pts at high risk for progression of joint damage (high disease activity including elevated hsCRP, presence of baseline erosions and ACPA and/or RF positivity<sup>2,3</sup>). The mean changes (Δ) from baseline (BL) in modified Total Sharp Score (mTSS), joint space narrowing (JSN), and erosion scores (ES) as well as the proportion of pts with no radiographic progression (ΔmTSS ≤0) at Weeks 24/26 and 48 were determined in both RCTs. Data were analyzed by linear extrapolation (LE) for missing data imputation and treatment switching, and as observed (AO). <h3>Results</h3> BL demographics have been reported previously<sup>2,3</sup>. At Weeks 24/26, UPA as monotherapy and in combination with background MTX significantly inhibited radiographic progression measured by mean ΔmTSS and the proportion of pts with no radiographic progression vs MTX and PBO, respectively (LE and AO, <b>Table</b>). The significant inhibition of radiographic progression with UPA was maintained through Week 48 vs MTX (LE and AO) in EARLY and vs PBO (LE) in COMPARE. Following the switch of all PBO pts to UPA in COMPARE by Week 26, no further change in mean mTSS was observed through Week 48 (AO,<b> Table</b>). The inhibition of radiographic progression vs comparators was not only observed for the overall mTSS scores but also its components – the JSN and ES in both RCTs (LE and AO). <h3>Conclusion</h3> UPA both as monotherapy, and in combination with background MTX, was effective in inhibiting the progression of structural joint damage through Week 48 in MTX-naïve, and MTX-IR patients, respectively. <h3>References</h3> [1] Smolen JS et al. Ann Rheum Dis 2017;0: 1–18.&#xD; [2] van Vollenhoven R, et al. Arthritis Rheumatol. 2018; 70(suppl 10) [ACR 2018abstract]. [3] Fleischmann R, et al. Arthritis Rheumatol. 2018; 70 (suppl 10) [ACR2018abstract]. <h3>Acknowledgement</h3> AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis, interpretation, writing, reviewing, and approval of the final version of the abstract. Medical writing support: Siddharth Mukherjee, PhD, from Abbvie, Inc. <h3>Disclosure of Interests</h3> Charles Peterfy Shareholder of: Spire Sciences, Inc, Consultant for: AbbVie, Acerta, Amgen, AstraZeneca, Bristol-Myers Squibb, Centrexion, Daiichi Sankyu, Five Prime Therapeutics, Genentech, Hoffmann-La Roche, Janssen, Lilly USA, MedImmune, Merck, Novartis, Plexxikon, Pfizer, Sanofi, Salix-Santarus, Samsung, Employee of: Spire Sciences, Inc, Speakers bureau: Amgen, Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, In-Ho Song Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie, Stephen Hall Grant/research support from: AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis, Consultant for: AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis , Eduardo Mysler Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Janssen, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lily, Janssen, Medimmune, Pfizer Inc, and Roche, Patrick Durez Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Sanofi, Celltrion, Xenofon Baraliakos Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Pfizer, Merck Sharp &amp; Dohme, UCB Pharma, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Janssen Biologics, Novartis, Pfizer, UCB Pharma, Galapagos, Speakers bureau: AbbVie, Chugai, Janssen, Novartis, Pfizer, UCB Pharma, Jose Jeffrey Enejosa Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Tim Shaw Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, Su Chen Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Vibeke Strand Consultant for: AbbVie, Amgen, Bayer, BMS, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, Genentech/Roche, GSK, Horizon, Inmedix, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Servier, UCB.