Background: For patients with rheumatoid arthritis (RA), long-term prevention of structural joint damage is a key treatment goal.1 In the SELECT-EARLY and SELECT-COMPARE trials, upadacitinib (UPA), an oral JAK inhibitor, inhibited the progression of structural joint damage at 6 months and 1 year when used either as monotherapy or in combination with methotrexate (MTX) in patients (pts) with active RA.2
Objectives: To describe the radiographic progression up to 2 years (96 wks) among pts with RA receiving UPA either as monotherapy or in combination with MTX.
Methods: Both the SELECT-EARLY and SELECT-COMPARE phase 3, randomized controlled trials enrolled pts at high risk for progressive structural damage with baseline (BL) erosive joint damage and/or seropositivity.3,4 In SELECT-EARLY, MTX-naïve pts (N=945) were randomized to UPA 15 mg or 30 mg once daily (QD) or MTX monotherapy. In SELECT-COMPARE, pts with an inadequate response to MTX (N=1629) were randomized to UPA 15 mg, placebo (PBO), or adalimumab (ADA) 40 mg every other wk, with all pts continuing background MTX; at wk 26, all pts receiving PBO were switched to UPA 15 mg, regardless of response. In both trials, mean changes from BL in modified Total Sharp Score (mTSS), joint space narrowing, and joint erosion as well as the proportion of pts with no radiographic progression (change in mTSS ≤0) were evaluated based on X-rays taken at wks 24/26, 48, and 96 for those patients in whom wk 96 X-rays were available. Data are reported as observed (AO).
Results: BL demographics have been reported previously.3,4 In the SELECT-EARLY study, at wk 96 UPA monotherapy (15 mg and 30 mg doses) significantly inhibited radiographic progression compared with MTX as measured by mean change in mTSS and by the proportion of patients with no radiographic progression (Figures 1 and 2). When patients who were rescued (MTX added to UPA or UPA added to MTX) were removed from the analysis, changes in mTSS from baseline remained similar. By the same measures, in SELECT-COMPARE, the degree of inhibition of structural progression observed was comparable between UPA and ADA. Following the switch of all PBO patients to UPA, the rate of progression slowed and was comparable to that observed in pts receiving UPA from BL. Among pts from both studies that had no radiographic progression at wk 24/26, >90% remained without radiographic progression at wk 48 and 96.
Conclusion: UPA was effective in inhibiting the progression of structural joint damage through 2 years both in MTX-naïve patients receiving UPA monotherapy and MTX-inadequate responder patients receiving UPA in combination with MTX.
References: Smolen, et al. Ann Rheum Dis 2017;76(6):960-77.
Peterfy, et al. Ann Rheum Dis 2019;78(suppl 2):369-370.
Fleischmann, et al. Arthritis Rheumatol 2019;71(11):1788-1800.
Van Vollenhoven, et al. Arthritis Rheumatol 2018;70(suppl 10).
Disclosure of Interests: : Charles Peterfy Consultant of: AbbVie, Acerta, Amgen, AstraZeneca, Bristol Myers Squibb, Centrexion, Daiichi Sankyo, Five Prime Therapeutics, Genentech, Gilead, Hoffman-La Roche, Janssen, Lilly USA, MedImmune, Merck, Myriad, Novartis, Plexxikon, Pfizer, Sanofi, Salix Santarus, Samsung, Samumed, Setpoint, Sorrento, UCB, Vorso, Employee of: founder and CEO of Spire Sciences, which provides imaging services to multiple pharmaceutical companies, Speakers bureau: Amgen, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, 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, Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Jose Jeffrey Enejosa Shareholder of: AbbVie, Employee of: AbbVie, Stephen Hall Grant/research support from: Abbvie, UCB, Janssen, Merck, Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Tim Shaw Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.
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