Inhibition of Structural Joint Damage with Upadacitinib as Monotherapy or in Combination with Methotrexate in Patients with Rheumatoid Arthritis

Charles Peterfy¹, Mark Genovese ², In-Ho Song ³, Alan Friedman ⁴, Stephen Hall ⁵, Eduardo Mysler ⁶, Patrick Durez ⁷, Xenofon Baraliakos ⁸, Jose Jeffrey Enejosa ⁹, Tim Shaw ⁴, Yihan Li ⁹, Su Chen ⁴ and Vibeke Strand ¹⁰, ¹Spire Sciences Inc, Boca Raton, ²Stanford University, Stanford, CA, ³AbbVie Inc., North Chicago, IL, USA, North Chicago, IL, ⁴AbbVie Inc., North Chicago, ⁵Monash University and Emeritus Research, Melbourne, Australia, ⁶Organización Medica de Investigación, Buenos Aires, Argentina, Buenos Aires, Argentina, ⁷Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, UCL Saint-Luc, Brussels, Belgium, ⁸Rheumatology Department, Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Bochum, Germany, ⁹AbbVie Inc., North Chicago, IL, ¹⁰Division of Immunology/Rheumatology, Stanford University, Stanford, CA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: rheumatoid arthritis, treatment and Janus kinase (JAK)

Session Information

Date: Sunday, November 10, 2019

Session Title: RA – Treatments Poster I: Novel Treatments

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Long‑term prevention of structural joint damage is a key treatment goal in the management of RA¹. 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)² and in combination with MTX in pts with inadequate response (IR) to MTX³.

We 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.

Methods: Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs), as previously described^2,3. 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^2,3). 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 (∆mTSS ≤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^2,3. 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, Table). 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, Table). 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.

REFERENCES:
1. Smolen JS et al. Ann Rheum Dis 2017;0: 1–18
2. van Vollenhoven R et al. Arthritis Rheumatol. 2018; 70 -suppl 10- [ACR 2018 abstract]
3. Fleischmann R et al. Arthritis Rheumatol. 2018; 70 -suppl 10- [ACR 2018 abstract]

Disclosure: C. Peterfy, AbbVie, 5, Acerta, 5, Amgen, 5, 8, AstraZeneca, 5, Bristol-Myers Squibb, 5, 8, Centrexion, 5, Crescendo Bioscience, 5, Daiichi Sankyo, 5, Daiichi Sankyu, 5, EMD Serono, 5, Five Prime, 5, Five Prime Therapeutics, 5, Flexion Therapeutics, 5, Genentech, 5, Genescence, 5, Gilead, 5, GlaxoSmithKline, 5, Hoffmann-La Roche, 5, Janssen, 5, Lilly, 5, MedImmune, 5, Merck, 5, Modern Bioscience, 5, Novartis, 5, Pfizer, 5, Plexikkon, 5, Plexxikon, 5, Regeneron, 5, Roche, Salix-Santarus, 5, Samsung, 5, Sanofi, 5, SetPoint, 5, Sorrento, 5, Spire Sciences, Inc., 1, 3, 4; M. Genovese, AbbVie, 2, 5, Abbvie, 2, 5, AbbVie, Inc., 9, Astellas, 2, 5, Eli Lilly, 2, 5, Eli Lilly and Company, 2, 5, EMD Merck Serono, 2, 5, Galapagos, 2, 5, Galapagos NV, 2, 5, 9, Genentech/Roche, 2, 5, Gilead, 2, 5, Gilead Science, 9, Gilead Sciences, Inc., 2, 5, 9, GSK, 5, Lilly, 2, 5, 9, Novartis, 2, 5, Pfizer, 2, 5, 9, Pfizer Inc, 2, 5, Pfizer, Inc., 9, Pzier, 9, RPharm, 5, Sanofi Genzyme, 2, 5, Vertex, 2, 5; I. Song, AbbVie, 3, 4; A. Friedman, AbbVie, 1, 3, Abbvie, 1, 4; S. Hall, AbbVie, 2, 5, BMS, 2, 5, Eli Lilly, 2, 5, Janssen, 2, 5, Lilly, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, UCB, 2, 5, UCB Pharma, 2, 5; E. Mysler, AbbVie, 2, 5, 8, BMS, 2, 5, Bristol-Myers Squibb, 2, 8, Eli Lilly, 2, 8, Janssen, 2, 8, Lilly, 2, 5, Novartis, 2, 8, Pfizer, 2, 5, 8, Roche, 2, 5, 8, Sandoz, 2, 5; P. Durez, BMS, 8, Bristol-Myers Squibb, 8, Celltrion, 8, Eli Lilly, 8, Hospira, 8, Mundipharma, 8, Pfizer, 8, Samsung, 8, Sanofi, 8, UCB, 8; X. Baraliakos, AbbVie, 2, 4, 5, 8, Biocad, 2, 5, Bristol-Myers Squibb, 2, 4, 5, 8, Celgene, 2, 5, 8, Chugai, 2, 5, Eli Lilly, 2, 5, Galapagos, 2, 5, 8, Janssen, 2, 5, 8, Lilly, 2, 5, 8, MSD, 2, 5, Novartis, 2, 5, 8, Pfizer, 2, 5, 8, Roche, 2, 5, UCB, 2, 5, 8; J. Enejosa, AbbVie, 3, 4; T. Shaw, Abbvie, 1, 4, AbbVie, 3, 4; Y. Li, AbbVie, 3, 4; S. Chen, AbbVie, 3, 4; V. Strand, Abbvie, 5, AbbVie, 5, Amgen, 5, Amgen, Abbvie, Bayer, BMS, Boehringer Ingelheim, Celltrion, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, UCB, 5, AstraZeneca, 5, AURA, 8, Bayer, 5, BMS, 5, Boehringer Ingelheim, 5, Celgene, 5, Celltrion, 5, Cleveland Clinic, 8, CORRONA, 5, Crescendo, 5, Crescendo Bioscience, 5, Eli Lilly, 5, EMD Serono, 5, Genentech, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 5, Inmedix, 5, Janssen, 5, Kezar, 5, Lilly, 5, Merck, 5, NACCME, 8, Novartis, 5, Pfizer, 5, Purdue, 8, RA Forum, 8, RAN, 8, Regeneron, 5, Roche, 5, Samsung, 5, Sandoz, 5, Sanofi, 5, Servier, 5, Setpoint, 5, SLRA, 8, UCB, 5, Up to Date, 7, Washington University, 8, WIR, 8, WRA, 8.

To cite this abstract in AMA style:

Peterfy C, Genovese M, Song I, Friedman A, Hall S, Mysler E, Durez P, Baraliakos X, Enejosa J, Shaw T, Li Y, Chen S, Strand V. Inhibition of Structural Joint Damage with Upadacitinib as Monotherapy or in Combination with Methotrexate in Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/inhibition-of-structural-joint-damage-with-upadacitinib-as-monotherapy-or-in-combination-with-methotrexate-in-patients-with-rheumatoid-arthritis/. Accessed November 13, 2019.

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