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  1. Mark C. Genovese1,
  2. Roy Fleischmann2,
  3. Ricardo Blanco3,
  4. Stephen Hall4,
  5. Glen Thomson5,
  6. Filip van den Bosch6,
  7. Cristiano Zerbini7,
  8. Jose Jeffrey Enejosa8,
  9. LI Yihan8,
  10. Ryan Demasi8,
  11. In-Ho Song8
  1. 1Stanford University, Palo Alto, United States of America
  2. 2Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, United States of America
  3. 3Hospital Universitario Marqués de Valdecilla, Santander, Spain
  4. 4Monash University, Cabrini Health and Emeritus Research, Malvern, Australia
  5. 5CIADS Research, Winnipeg, Canada
  6. 6Ghent University Hospital, Ghent, Belgium
  7. 7Paulista Center for Clinical Research, São Paulo, Brazil
  8. 8AbbVie, Inc., North Chicago, United States of America


Background Initiating advanced therapy for rheumatoid arthritis (RA) patients (pts) with a bDMARD or a Janus kinase (JAK) inhibitor is recommended if remission or low disease activity (LDA) is not achieved with csDMARDs.1,2 While data show that pts are switched alternately between bDMARD and JAK treatments, there is lack of evidence for pts with inadequate response (IR) to a JAK inhibitor switching to a bDMARD. Recently, the JAK1-selective inhibitor-upadacitinib (UPA) demonstrated superior clinical and functional outcomes through 26 wks to the standard of care-adalimumab (ADA) with continued background methotrexate (MTX).3

Objectives To describe outcomes associated with treatment switch from UPA to ADA and vice-versa among RA pts who do not achieve initial response.

Methods This phase 3, double-blind, placebo (PBO)-controlled, head-to-head study of UPA 15 mg q.d. vs PBO or ADA 40 mg injection every other wk included MTX-IR patients; all pts continued stable background MTX through 26 wks. Pts without ≥20% improvements from bl in tender (68) and swollen (66) joint counts by wks 14, 18, or 22 were considered non-responders (NR) and switched without washout to either ADA (UPA group) or UPA (ADA group) in a bl fashion. Post-hoc analysis assessed clinical outcomes - DAS28 (CRP), CDAI, SDAI, and ACR responses (from baseline), and HAQ-DI at 3 and 6 mos (±2 wks) post-switch. Adverse events (infections) were summarized as n% (95% CI) through 6 mos post-switch (ps). Data were as observed.

Results Of the 651 and 327 pts randomized to receive UPA and ADA, 126 (19%) and 77 (24%), were considered NR and switched to ADA and UPA respectively. NR demographics were consistent with the overall randomized population. Of the switched pts, ∼90% remained in the study through 6 mo ps. Patients switched to ADA (UPA-NR) achieved 59%/26%/12% improvements in ACR20/50/70 responses, and 35% achieved DAS28(CRP) ≤3.2 at 6 mos ps (Table). Patients switched to UPA (ADA-NR) achieved 75%/49%/24% improvements in ACR20/50/70, and 54% achieved DAS28(CRP) ≤3.2 at 6 mo- consistent with data observed in a phase 3 study of UPA in bDMARD-IR RA pts.4 The proportion (95% CI) of pts with infection and serious infection through 6 mos ps appeared consistent with those observed for ADA and UPA during comparable periods (ADA, switched from UPA: infection: 34.1 [26.43, 42.77], serious infection: 1.6 [0.44, 5.60]; UPA, switched from ADA: infection: 40.3 [30.02, 51.42], serious infection: 3.9 [1.33, 10.84]

Conclusion Data from this blinded, controlled study indicate that pts with initial non-response to either UPA or ADA can benefit from switching to the other therapy. No additional safety concerns were observed. These are the first data to demonstrate effectiveness of a TNF inhibitor following failure of a JAK inhibitor.

References [1] Smolen, et al. Ann Rheum Dis, 2017;76:1113-36.

[2] Singh, et al. Arthritis Rheumatol, 2016;68:1-26.

[3] Fleischmann, et al. Arthritis Rheumatol, 2018;70(Suppl 10).

[4] Genovese, et al. Lancet, 2018;391:2513-24.

Acknowledgement AbbVie funded the study, contributed to its design, data collection, analysis, interpretation, writing, reviewing, and approval of the final version of this abstract. Medical writing support: Dalia Majumdar, PhD, and Benjamin Wolfe, PhD, of Abbvie.

Disclosure of Interests Mark C. Genovese Grant/research support from: Sanofi/Genzyme, Genentech/Roche, RPharm, Consultant for: Sanofi/Genzyme, Genentech/Roche, RPharm, Roy Fleischmann Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Consultant for: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celtrion, Genentech, GSK, Janssen, Lilly, Novartis, Pfizer Inc, Sanofi-Aventis, UCB, Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, 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, Glen Thomson Grant/research support from: AbbVie, Consultant for: Amgen, Filip van den Bosch Consultant for: AbbVie, BMS, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer and UCB, Speakers bureau: AbbVie, BMS, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Cristiano Zerbini Grant/research support from: Amgen, Celltrion, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer Inc., and Sanofi, Consultant for: Eli Lilly, Pfizer Inc., and Sanofi., Jose Jeffrey Enejosa Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Yihan Li Shareholder of: AbbVie, Employee of: AbbVie, Ryan DeMasi Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, In-Ho Song Shareholder of: AbbVie Inc, Employee of: AbbVie Inc

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