POS0653 IMPACT OF UPADACITINIB OR ADALIMUMAB AS INITIAL THERAPY ON THE ACHIEVEMENT OF 48-WEEK TREATMENT GOALS IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE TO METHOTREXATE: POST HOC ANALYSIS OF A PHASE 3 STUDY
Authors: E. Mysler, Y. Tanaka, A. Kavanaugh, D. Aletaha, P. C. Taylor, I. H. Song, T. Shaw, Y. Song, R. Demasi, M. Ali, R. Fleischmann
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the randomized, double-blinded, Phase 3 SELECT-COMPARE study, upadacitinib (UPA) + MTX demonstrated greater clinical and functional responses vs adalimumab (ADA) + MTX in patients (pts) with RA and inadequate response to MTX. 1,2 Pts with insufficient response to initial therapy were switched from UPA to ADA (and vice versa) according to treat-to-target (T2T) principles. Objectives: We analyzed 1-year treatment outcomes in SELECT-COMPARE according to initial randomization group, regardless of whether pts subsequently switched therapy. Methods: Pts initially randomized to UPA 15 mg once daily (QD) or ADA 40 mg every other week (EOW; both + MTX) for up to 48 weeks in SELECT-COMPARE were included in the analysis. As per the protocol-directed rescue strategy, pts experiencing &lt;20% improvement in tender or swollen joint counts at Week 14, 18, or 22, or Clinical Disease Activity Index (CDAI) &gt;10 at Week 26, were switched from UPA to ADA or ADA to UPA in a blinded fashion. Efficacy outcomes included CDAI remission (≤2.8) and low disease activity (LDA; ≤10), DAS of 28 joints using CRP (DAS28[CRP]) &lt;2.6 and ≤3.2, and a composite of “deep response” (CDAI remission, HAQ-Disability Index &lt;0.5, and pain score &lt;20). Data are presented and attributed to initial randomized group (UPA or ADA) regardless of any subsequent switch in therapy. Time-averaged response rates were calculated as area under the curve of response rate standardized by 48 weeks. The proportions of pts who maintained Week 26 responses through 6 months of follow-up are also reported. Results: This analysis included 651 pts initially randomized to UPA (of whom 245 switched to ADA) and 327 pts initially randomized to ADA (of whom 157 switched to UPA). Baseline characteristics including age, sex, and BMI were generally well balanced between randomized groups. At Week 48, similar proportions of pts initially randomized to UPA or ADA therapy achieved CDAI remission/LDA (27.6%/61.9% vs 24.8%/59.0%) and DAS28(CRP) &lt;2.6/≤3.2 (45.0%/60.2% vs 43.7%/59.0%) (Figure 1). However, a small but significantly greater proportion of pts achieved a deep response with initial UPA vs initial ADA therapy (17.8% vs 12.8%; p&lt;0.05). In addition, time-averaged response rates over 48 weeks were higher for initial UPA vs initial ADA therapy across efficacy outcomes. Similar trends were observed for other outcomes. Additionally, similar proportions of pts maintained Week 26 responses with initial UPA vs initial ADA therapy based on CDAI remission/LDA and DAS28(CRP) &lt;2.6/≤3.2 during 6-month follow-up (Table 1). Conclusion: Using a stringent T2T approach to RA management, rates of LDA or remission at 1 year were similar, regardless of whether pts were initially randomized to UPA or ADA. However, initial UPA therapy led to more frequent deep responses and higher time-averaged response rates vs initial ADA therapy. References: [1]Fleischmann R, et al. Arthritis Rheumatol 2019;71:1788–800. [2]Fleischmann R, et al. Ann Rheum Dis 2019;78:1454–62. Table 1. Proportion of patients maintaining Week 26 CDAI and DAS28(CRP) responses during 6-month follow-up by initial therapy with UPA or ADA in SELECT-COMPARE a-c UPA 15 mg QD ADA 40 mg EOW CDAI LDA (≤10) 43.9 36.3 CDAI Remission (≤2.8) 35.0 22.7 DAS28(CRP) ≤3.2 39.1 35.3 DAS28(CRP) &lt;2.6 30.5 30.1 a As observed. b Blinded rescue from UPA to ADA or ADA to UPA was permitted at Week 14, 18, and 22 for patients with &lt;20% improvement in TJC or SJC and at Week 26 for patients with a CDAI &lt;10. Data are presented and attributed to original randomized group (UPA or ADA) regardless of any subsequent switch in therapy. c Maintaining response defined as never losing response at any visit during ~6 months (22–26 weeks) follow up after first achieving response before or at Week 26. ADA, adalimumab; CDAI, Clinical Disease Activity Index; DAS28(CRP), DAS of 28 joints using CRP; EOW, every other week; QD, once daily; SJC, swollen joint count; TJC, tender joint count; UPA, upadacitinib. Acknowledgements: AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing assistance was provided by Frances Smith, PhD, of 2 the Nth, which was funded by AbbVie. Disclosure of Interests: Eduardo Mysler Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and Sandoz., Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and Sandoz., Yoshiya Tanaka Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Eli Lilly, Chugai, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics, Consultant of: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Eli Lilly, Chugai, Daiichi-Sankyo, Eisai, Gilead, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics, Grant/research support from: AbbVie, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Takeda, and UCB., Arthur Kavanaugh Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Pfizer, Roche, and UCB., Grant/research support from: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Janssen, Pfizer, Roche, and UCB., Daniel Aletaha Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB., Grant/research support from: AbbVie, Amgen, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB., Peter C. Taylor Speakers bureau: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Fresenius, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB., Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Fresenius, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB., Grant/research support from: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Fresenius, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB., In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie, Tim Shaw Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie, Employee of: AbbVie, Ryan DeMasi Shareholder of: AbbVie, Employee of: AbbVie, Mira Ali Shareholder of: AbbVie, Employee of: AbbVie, Roy Fleischmann Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Aventis, and UCB., Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Aventis, and UCB.