P225 Inhibition of structural joint damage with upadacitinib as monotherapy or in combination with MTX in patrients with RA: one-year outcomes from the select Phase 3 programme
Authors: Peterfy Charles , Genovese Mark C , Song In-Ho , Friedman Alan , Hall Stephen , Mysler Eduardo , Durez Patrick , Baraliakos Xenofon , Enejosa Jose Jeffrey , Shaw Tim , Li Yihan , Chen Su , Strand Vibeke 
Published: April 2020

Abstract

Background
Long-term prevention of structural joint damage is a key treatment goal in the management of RA. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)-naïve RA patients and in combination with MTX in patients with inadequate response (IR) to MTX. Objectives: To evaluate the progression of structural joint damage (radiographic) through Week 48 in patients with moderately to severely active RA treated with UPA monotherapy or in combination with MTX.

Methods
Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs). MTX-naïve patients were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT-EARLY, N = 945], while MTX-IR patients 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 patients at high risk for progression of joint damage (high disease activity including elevated hsCRP, presence of baseline erosions and ACPA and/or RF positivity). The mean changes (D) from baseline (BL) in modified Total Sharp Score (mTSS), joint space narrowing (JSN), and erosion scores (ES) as well as the proportion of patients 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).

Results
BL demographics have been reported previously. At Weeks 24/26, UPA as monotherapy and in combination with background MTX significantly inhibited radiographic progression measured by mean DmTSS and the proportion of patients with no radiographic progression vs MTX and PBO, respectively. 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 patients to UPA in COMPARE by Week 26, no further change in mean mTSS was observed through Week 48. 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).

Conclusion
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.

Disclosures
C. Peterfy: Consultancies; 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. M.C. Genovese: Consultancies; Consultant for and has received grants from AbbVie Inc, Lilly, Pfizer, Galapagos, and Gilead. I. Song: Corporate appointments; Employee of AbbVie. A. Friedman: Corporate appointments; Employee of AbbVie. S. Hall: Consultancies; Received research grants and consultancy fees from AbbVie Inc, BMS, Lilly, Janssen, Pfizer, UCB, and Novartis. E. Mysler: Grants/research support; Received research grants and speaker’s bureau fees from Bristol-Myers Squibb, Roche, Eli Lilly, AbbVie, Novartis, Janssen, and Pfizer. P. Durez: Member of speakers’ bureau; Bristol-Myers Squibb, Samsung, Pfizer, UCB, Mundipharma, Hospira, and Eli Lilly. X. Baraliakos: Grants/research support; AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Chugai, Janssen, MSD, Novartis, Pfizer Inc, Roche and UCB. J. Enejosa: Corporate appointments; Employee of AbbVie. T. Shaw: Corporate appointments; Employee of AbbVie. Y. Li: Corporate appointments; Employee of AbbVie. S. Chen: Corporate appointments; Employee of AbbVie. V. Strand: Consultancies; Consultant for AbbVie, Amgen, AstraZeneca, BMS, Celltrion, Celgene, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB.