OP0029 SWITCHING BETWEEN THE JAK1-SELECTIVE INHIBITOR-UPADACITINIB AND ADALIMUMAB FOLLOWING INITIAL NON-RESPONSE: CLINICAL AND FUNCTIONAL OUTCOMES AMONG RHEUMATOID ARTHRITIS PATIENTS
Authors: Mark C. Genovese, Roy Fleischmann, Ricardo Blanco, Stephen Hall, Glen Thomson, Filip van den Bosch, Cristiano Zerbini, Jose Jeffrey Enejosa, LI Yihan, Ryan Demasi, In-Ho Song
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> 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.<sup>1,2</sup> 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).<sup>3</sup> <h3>Objectives</h3> To describe outcomes associated with treatment switch from UPA to ADA and vice-versa among RA pts who do not achieve initial response. <h3>Methods</h3> 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. <h3>Results</h3> 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 (<b>Table</b>). 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.<sup>4</sup> 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] <h3>Conclusion</h3> 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. <h3>References</h3> [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. <h3>Acknowledgement</h3> 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. <h3>Disclosure of Interests</h3> 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