Abstract: Upadacitinib (UPA) was shown to be safe and effective through 2 years in patients (pts) with active ankylosing spondylitis (AS) naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) in the pivotal phase 2/3 SELECT-AXIS 1 trial. 1,2 Objectives To assess the efficacy and safety of UPA in pts with active AS with an inadequate response (IR) to bDMARDs. Methods SELECT-AXIS 2 ( NCT04169373 ) was conducted under a master protocol and includes two separate studies (one for AS bDMARD-IR and one for non-radiographic axial spondyloarthritis [nr-axSpA]). The AS bDMARD-IR study is a randomized, double-blind, placebo (PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with AS who met modified New York criteria, had BASDAI and pt’s assessment of total back pain scores ≥4 (numeric rating scale 0–10) at study entry, and had an IR to one or two bDMARDs (TNF inhibitor or IL-17 inhibitor). Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during the 14-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints evaluated at wk 14 were improvements from baseline in disease activity (ASDAS [CRP] , ASDAS ID [ 〈 1.3], ASDAS LDA [ 〈 2.1], BASDAI50, ASAS20, and ASAS PR), pain (total and nocturnal back pain), function (BASFI), objective measure of inflammation (SPARCC MRI score of the spine), spinal mobility (BASMI), enthesitis (MASES), and quality of life (ASQoL and ASAS HI). Non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle intercurrent events and missing data for binary endpoints. Cochran-Mantel-Haenszel (CMH) test and mixed-effect model for repeated measures (MMRM) were used for analyzing binary and continuous endpoints, respectively. Treatment-emergent adverse events (TEAEs) assessed through wk 14 are reported for pts who had ≥1 dose of study drug. Results All 420 randomized pts with active AS received assigned treatment (UPA 15 mg, n=211; PBO, n=209); 409 (97%) received study drug through wk 14. Baseline demographic and disease characteristics were generally similar between treatment groups and reflective of an active AS bDMARD-IR population (74% male; mean age 42.4 years; mean disease duration 7.7 years; 83% HLA-B27 positive; mean BASDAI 6.8). Significantly more pts achieved the primary endpoint of ASAS40 response at wk 14 with UPA vs PBO (45% vs 18%; P 〈 0.0001; Figure 1); UPA showed onset of effect in ASAS40 as early as wk 4 (nominal P ≤0.05). All multiplicity-controlled secondary endpoints met statistical significance for UPA vs PBO at wk 14 across multiple clinical domains of AS ( P 〈 0.0001; Figure 1). The rate of TEAEs was similar between treatment groups through wk 14 (UPA, 41%; PBO, 37%). TEAEs led to discontinuation in 3 (1.4%) pts treated with PBO and none with UPA. Serious infections occurred with UPA (2.4%) but not with PBO and included 4 events of COVID-19 and 1 event of uveitis. Additional events of uveitis were reported in 3 (1.4%) pts treated with PBO. Inflammatory bowel disease (IBD) occurred in 1 (0.5%) pt on UPA and none on PBO. No malignancy, major adverse cardiovascular events, venous thromboembolic events, or death were reported with UPA; 1 event of malignancy was observed with PBO. Conclusion UPA 15 mg QD was significantly more effective than PBO over 14 wks of treatment in pts with active AS and IR to bDMARDs. No new safety risks were identified with UPA compared with its known safety profile. 3,4 These findings are consistent with and complementary to those of SELECT-AXIS 1 (bDMARD-naïve AS population), 1,2 and support the use of UPA in pts with active AS, including those who had a previous IR to bDMARD therapy. References [1]van der Heijde D, et al. Arthritis Rheumatol . 2021;73(suppl 10). [2]van der Heijde D, et al. Lancet . 2019;394(10214):2108–2117. [3]Cohen SB, et al. ARD . 2021;80:304–311. [4]Burmester G, et al. Rheumatol Ther . 2021;1–19. Acknowledgements AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie. Disclosure of Interests Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, and Werfen, Grant/research support from: AbbVie, Novartis, Joachim Sieper Speakers bureau: AbbVie, Janssen, Merck, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck, and Pfizer, Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, GSK, Lilly, Novartis, Pfizer, and UCB, Robert Inman Consultant of: AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and Sandoz, Grant/research support from: AbbVie, Amgen, and Janssen, Hideto Kameda Speakers bureau: AbbVie, Asahi-Kasei, BMS, Chugai, Eisai, Janssen, Lilly, Mitsubishi-Tanabe, Novartis, and Pfizer, Consultant of: AbbVie, Janssen, Lilly, Novartis, Sanofi, and UCB, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Eisai, and Mitsubishi-Tanabe, Xiaofeng Zeng: None declared, Yunxia Sui Shareholder of: May own AbbVie stock or options, Employee of: AbbVie, Xianwei Bu Shareholder of: May own AbbVie stock or options, Employee of: AbbVie, Aileen Pangan Shareholder of: May own AbbVie stock or options, Employee of: AbbVie, Peter Wung Shareholder of: May own AbbVie stock or options, Employee of: AbbVie, In-Ho Song Shareholder of: May own AbbVie stock or options, Employee of: AbbVie

Abstract: Guselkumab (GUS), an interleukin-23 inhibitor, was efficacious in reducing signs and symptoms of active psoriatic arthritis (PsA) in patients (pts) in two phase 3 trials (DISCOVER-1 and DISCOVER-2). Objectives: To evaluate the efficacy of GUS in PsA pts with imaging-confirmed axial involvement consistent with sacroiliitis in DISCOVER-1 & 2. Methods: In DISCOVER-1, 381 pts with active PsA (≥ 3 swollen joints, ≥ 3 tender joints; C-reactive protein ≥ 0.3mg/dL despite standard therapies) and in DISCOVER-2, 739 pts with active PsA (≥ 5 swollen joints, ≥ 5 tender joints, CRP ≥ 0.6mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100mg Q4W, GUS 100mg Q8W (Wk0, Wk4, then Q8W), or PBO. This analysis included pts with sacroiliitis at baseline who had either documented imaging confirmation of sacroiliitis in the past or pelvic X-ray confirmation of sacroiliitis at screening (pooled data from DISCOVER-1 & 2) based on investigators’ judgment of presence/absence of sacroiliitis. Efficacy was assessed by BASDAI score, BASDAI50, modified BASDAI (mBASDAI; excludes Q#3), spinal pain (BASDAI Q#2), ASDAS-CRP score, and ASDAS responses of inactive disease ( 〈 1.3), major improvement (decrease ≥2.0), and clinically important improvement (decrease ≥1.1). Pts with missing data at wk24 were classified as nonresponders. Results: 312 pts presented with axial involvement (PBO, n= 118; GUS q8w, n = 91; GUS q4w, n = 103). The LS mean changes from baseline to wk24 in BASDAI, spinal pain, mBASDAI, and ASDAS-CRP were greater in the two GUS groups vs PBO (Table). Greater proportions of GUS-treated pts achieved BASDAI50 (Table) and ASDAS responses of inactive disease, major improvement, and clinically important improvement (Figure) at wk24 vs PBO. Conclusion: GUS improved axial symptoms over 24 weeks in active PsA patients with imaging-confirmed sacroiliitis. Table. Efficacy of GUS in PsA patients with axial involvement at week 24. a PBO (n=118) GUS 100 mg every 8 weeks (n=91) GUS100 mg every 4 weeks (n=103) LS Mean change in BASDAI -1.35 -2.67* -2.68* LS Mean change in spinal pain b -1.30 -2.73* -2.48* BASDAI50 c , % 21/110 (19.1%) 34/84 (40.5%)** 36/95 (37.9%)** LS Mean change in modified BASDAI d -1.13 -2.16* -2.18* LS Mean change in ASDAS-CRP -0.71 -1.43* -1.46* a Pts with axial involvement consistent with sacroiliitis at baseline and either a history of imaging confirmation or pelvic X-ray at screening (pooled data from DISCOVER-1 & 2) b Question 2 of the BASDAI. c Pts with BASDAI 〉 0 at baseline. d Excludes question 3 of the BASDAI. Unadjusted p-values as noted: *p 〈 0.001, ** p 〈 0.01 Acknowledgments: None Disclosure of Interests: Philip Helliwell: None declared, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, 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, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV

Abstract: Guselkumab (GUS), a selective IL-23p19 inhibitor, showed greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores vs placebo (PBO) at Week (W) 24 in patients (pts) with active PsA and investigator-confirmed sacroiliitis in pooled post hoc analyses of data from phase 3 DISCOVER (D)-1 & 2 trials. Improvements in symptoms of axial involvement were maintained through 1 year. 1 Objectives To assess maintenance of GUS effect on symptoms of axial involvement in biologic-naïve PsA pts with investigator-confirmed sacroiliitis through 2 years of D-2. Methods In D-2, 739 bio-naïve pts with active PsA (≥5 swollen + ≥5 tender joints, CRP ≥0.6 mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100 mg every 4W (Q4W; n=245), GUS 100 mg at W0, W4, then Q8W (n=248), or PBO (n=246) with PBO→GUS 100 mg Q4W at W24. Pts with investigator-identified axial symptoms and sacroiliitis (prior X-ray or MRI, or pelvic X-ray at screening) were evaluated. Efficacy was assessed by changes in BASDAI, modified BASDAI (mBASDAI, excluding Q3 [peripheral joint pain]), and BASDAI Q2 (Spinal Pain) scores, and proportions of pts achieving BASDAI 50, Spinal Pain score ≤2, and AS Disease Activity Score (ASDAS) responses through W100. Through W24, pts who met treatment failure criteria or had missing data were considered nonresponders. After W24, missing data were imputed as nonresponse for binary endpoints or no change from baseline for continuous endpoints (nonresponder imputation [NRI] ). Axial-related outcomes were also summarized by HLA-B27 status (+/-). Results 246 pts had investigator-confirmed sacroiliitis. Baseline characteristics were similar across treatment groups (62% male; mean age 44.4 years; mean BASDAI scores 6.5-6.6). At W24, LS mean/mean changes in BASDAI (-2.4/-2.6) and ASDAS (-1.3/-1.5) scores were greater in GUS- vs PBO-treated pts. Improvements were maintained through W100 in GUS-treated pts: BASDAI, -3.1; Spinal Pain, -3.1; mBASDAI, -3.1; ASDAS, -1.7. Response patterns were similar for BASDAI 50 response rates in GUS-treated pts (W24 38-40%; W100 49-54%). At W24, GUS-treated pts had higher response rates for achievement of ASDAS inactive disease, major improvement, and clinically important improvement vs PBO; response rates (NRI) were maintained, or in some cases further increased, at 2 years. Results were consistent for achievement of ASDAS LDA and Spinal Pain score ≤2 (data not shown). GUS-related improvements in axial symptoms through W100 were generally consistent in HLA-B27+/- pts (data not shown). Conclusion In bio-naïve pts with active PsA and investigator-confirmed sacroiliitis, GUS provided durable improvements in axial symptoms through W100, with substantial proportions of pts achieving and maintaining clinically meaningful improvements. References [1]Mease PJ et al. Lancet Rheumatol 2021;3:e715-723 Table 1. Axial symptom assessments through W100 in PsA pts with investigator-confirmed sacroiliitis in DISCOVER-2 (NRI ) GUS Q4W N=82 GUS Q8W N=68 PBO → GUS Q4W N=96 Change in BASDAI score W24 , LS mean (95% CI) -2.5 (-2.9, -2.0) -2.4 (-3.0, -1.8) -1.2 (-1.7, -0.7) Mean (SD) -2.5 (2.0) -2.6 (2.4) -1.4 (2.4) W52 , mean (SD) -2.9 (2.3) -2.7 (2.5) -2.9 (2.6) W100 , mean (SD) -3.0 (2.3) -3.1 (2.6) -3.3 (2.6) Change in mBASDAI (excludes Q3) score W24 , LS mean (95% CI) -2.4 (-2.9, -1.9) -2.4 (-2.9, -1.8) -1.2 (-1.7, -0.7) Mean (SD) -2.5 (2.1) -2.6 (2.5) -1.3 (2.3) W52 , mean (SD) -2.7 (2.6) -2.6 (2.5) -2.9 (2.4) W100 , mean (SD) -3.3 (2.6) -3.1 (2.6) -3.0 (2.4) Change in Spinal Pain (BASDAI Q2) score W24 , LS mean (95% CI) -2.2 (-2.7, -1.7) -2.3 (-2.9, -1.7) -0.9 (-1.5, -0.4) Mean (SD) -2.3 (2.6) -2.5 (2.8) -1.1 (2.5) W52 , mean (SD) -2.6 (2.7) -2.5 (2.7) -2.5 (2.7) W100 , mean (SD) -2.8 (2.7) -3.1 (2.8) -3.0 (2.8) Change in ASDAS score W24 , LS mean (95% CI) -1.3 (-1.6, -1.1) -1.3 (-1.6, -1.1) -0.6 (-0.8, -0.4) Mean (SD) -1.4 (1.0) -1.5 (1.2) -0.7 (1.1) W52 , mean (SD) -1.5 (1.1) -1.5 (1.3) -1.5 (1.3) W100 , mean (SD) -1.6 (1.2) -1.7 (1.2) -1.6 (1.2) Disclosure of Interests Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Philip Helliwell Speakers bureau: AbbVie, Janssen, and Novartis, Consultant of: Eli Lilly, Janssen, and Pfizer, Dafna D Gladman Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Denis Poddubnyy Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, MDS, Novartis, and Pfizer, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, Employee of: Imaging Rheumatology BV, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, and UCB

Abstract: Patients with ankylosing spondylitis (AS) are burdened with decreased work productivity. 1 Ixekizumab (IXE), a high-affinity monoclonal antibody selectively targeting interleukin-17A, has been shown to improve disease signs and symptoms in 2 phase 3 trials assessing patients with active AS. 2, 3 Objectives: This study investigated the effect of IXE treatment for 52 weeks on work productivity and activity impairment as measured by absenteeism, presenteeism, overall work impairment, and activity impairment in patients with active AS. Methods: COAST-V ( NCT02696785 ) and COAST-W ( NCT02696798 ) were phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled (COAST-V active-controlled with adalimumab) trials investigating the efficacy of IXE every 4 weeks (Q4W) and every 2 weeks (Q2W) in 341 patients with active AS naïve to biologic disease-modifying antirheumatic drugs (bDMARDs; COAST-V) and in 316 patients who were inadequate responders or intolerant to 1 or 2 tumor necrosis factor inhibitors (TNFi; COAST-W). Patients receiving PBO were switched to IXE Q4W or Q2W at Week 16; patients receiving adalimumab (ADA) were switched to IXE Q4W or Q2W at Week 20. Data for IXE Q4W and Q2W were combined for PBO/IXE and ADA/IXE groups. Changes from baseline in work productivity were measured for those reporting full- or part-time work at Weeks 16 and 52 with the Work Productivity and Activity Impairment (WPAI) Questionnaire for Spondyloarthritis. Results: Compared to bDMARD-naïve patients (COAST-V), TNFi-experienced patients (COAST-W) were slightly older, had longer disease duration, reported less paid employment, and had greater scores for impaired work productivity, signifying more severe baseline disease. At Week 16, bDMARD-naïve patients treated with IXE Q4W or Q2W had significant improvements in activity impairment compared to placebo (p 〈 0.01); TNFi-experienced patients treated with IXE Q4W or Q2W had significant improvements in presenteeism (p 〈 0.05) and overall work impairment (p 〈 0.05; Figure). TNFi-experienced patients treated with IXE Q2W also had significant improvement in activity impairment at Week 16 (p 〈 0.05; Figure). Improvements were sustained through Week 52 (Figure). Conclusion: Both bDMARD-naïve and TNFi-experienced patients with AS receiving IXE had greater improvements in aspects of work productivity compared to placebo. Improvements were sustained through Week 52. References: [1]Boonen, van der Linden. (2006). J Rheumatol Suppl. 78:4-11. [2]Van der Heijde, et al. (2018) Lancet . 392(10163):2441-51. [3]Deodhar, et al. (2019) Arthritis Rheumatol. 71(4):599-611. Disclosure of Interests: Helena Marzo-Ortega Grant/research support from: Janssen, Novartis, Consultant of: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB, 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, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, James Cheng-Chung Wei Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB Pharma, 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, Theresa Hunter Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Xiaoqi Li Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Baojin Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB Figure. Changes from baseline in Overall Work Impairment in A) bDMARD-naïve (COAST-V) and B) TNFi-experienced (COAST-W) patients and Activity Impairment in C) bDMARD-naïve and D) TNFi-experienced patients.

Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton associated with pain, stiffness, and disability. 1 Up to 66% of patients (pts) with AS may also have peripheral involvement, including swollen and tender joints (STJs), 2,3 which are associated with worse overall disease activity. 4 A previous analysis showed that secukinumab, a selective inhibitor of interleukin 17A, led to significant improvements in efficacy outcomes vs placebo, regardless of peripheral joint involvement. 3 However, the effect of secukinumab on symptoms of peripheral arthritis in pts with AS was not assessed. Objectives: The objective of this analysis was to assess changes in peripheral symptoms in pts with AS treated with secukinumab vs placebo. Methods: Data from pts with active AS and peripheral symptoms who were enrolled in MEASURE 1 ( NCT01358175 ), 2 ( NCT01649375 ), 3 ( NCT02008916 ), and 4 ( NCT02159053 ) were pooled in this post hoc, hypothesis-generating analysis. No adjustments for multiple comparisons were made. Pts with peripheral symptoms were identified by the presence of STJs, based on 44-joint counts at baseline (BL). Pts received subcutaneous (SC) secukinumab every 4 weeks at doses of 300 mg with an intravenous (IV) loading dose (MEASURE 3 only), 150 mg with an IV or SC loading dose, or placebo. Treatment response through Week 16 was assessed based on the proportions of pts who achieved improvements of 20%, 50%, 70%, or 100% in the number of swollen and number of tender joints and improvements in the BASDAI score for question 3 and Patient Global Assessment (PGA). Changes in the number of swollen and number of tender joints were assessed in pts with swollen or tender joints at BL, respectively. Results: This pooled analysis included 560 pts with AS and STJs at BL (Table). At Week 16, treatment with secukinumab led to significantly greater proportions of pts achieving reductions in the number of swollen (Fig 1A) or tender (Fig 1B) joints compared with placebo; the treatment effect was more pronounced in reduction of swollen joints. Furthermore, a greater proportion of secukinumab-treated pts achieved complete resolution of swollen or tender joints vs placebo (Fig 1). Secukinumab also led to significant improvements in peripheral pain/swelling (Fig 2A) and disease activity (Fig 2B) vs placebo, as assessed using BASDAI question 3 and the PGA, respectively. Table. Patient Characteristics at Baseline Secukinumab Placebo (n = 252 ) 300 mg (n = 52 ) 150 mg (n = 256 ) Age, mean, y 43.6 43.7 44.9 Time since diagnosis, mean, y 5.6 7.2 7.3 Male, % 63.5 62.1 57.5 PGA of Disease Activity, mean, mm 73.4 71.7 70.1 BASDAI question 3, mean 6.3 6.6 6.4 Swollen 44-joint count, mean 1.9 2.6 2.5 Tender 44-joint count, mean 7.1 7.8 7.9 Conclusion: In parallel with its previously reported efficacy in axial symptoms, 3 secukinumab led to significant improvements in symptoms of peripheral arthritis in pts with AS. Significant improvements were seen in both tender and swollen joints. References: [1]Braun J, Sieper J. Lancet . 2007;369:1379-1390. [2]de Winter JJ, et al. Arthritis Res Ther . 2016;18:196. [3]Mease P, et al. Arthritis Rheumatol . 2019;71(suppl 10):1553. [4]de Winter JJ, et al. RMD Open . 2019;5:e000802. Acknowledgments: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ. The authors thank Amos Race, PhD, of ArticulateScience LLC, Hamilton, NJ, USA, for providing medical writing/editorial support, which was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, in accordance with Good Publication Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ). Disclosure of Interests: Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Renato Calheiros Shareholder of: Novartis, Employee of: Novartis, Xiangyi Meng Shareholder of: Novartis, Employee of: Novartis, Todd Fox Shareholder of: Novartis, Employee of: Novartis, 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

Abstract: Bimekizumab (BKZ), a monoclonal antibody that selectively inhibits interleukin (IL)-17A and IL-17F, has demonstrated clinical efficacy and safety in patients with ankylosing spondylitis (AS) treated over a period up to 96 weeks. 1,2 Objectives: To report 3-year interim safety and efficacy of BKZ in patients with active AS from a phase 2b dose-ranging study (BE AGILE; NCT02963506 ) and its ongoing open-label extension (OLE; NCT03355573 ). Methods: BE AGILE study design has been described previously. 1 Patients treated with BKZ 160 mg or 320 mg every 4 weeks (Q4W) at Week 48 in BE AGILE were eligible for OLE entry. All OLE patients received BKZ 160 mg Q4W. Treatment-emergent adverse events (TEAEs) are reported for the BE AGILE safety set (patients who received ≥1 dose of BKZ on study entry) for total exposure to BKZ across BE AGILE and the OLE. Efficacy outcomes are reported for the OLE full analysis set (patients who entered the OLE and had ≥1 dose of BKZ and ≥1 valid efficacy variable measurement in the OLE), and include: ASAS40, ASAS20, ASAS PR, ASDAS, ASDAS-CII, ASDAS-MI, ASDAS-ID ( 〈 1.3) and ASDAS 〈 2.1. Data are reported as imputed (multiple imputation [MI] based on the missing at random assumption, or non-responder imputation [NRI] ) and as observed case (OC). Results: 262/303 (86%) patients randomised at BE AGILE study baseline completed Week 48 on BKZ 160 mg or 320 mg. At Week 48, 255/262 (97%) patients entered the OLE (full analysis set: 254); 219 patients had an efficacy assessment at Week 156. Over the 156 weeks, the exposure-adjusted incidence rate (EAIR) per 100 patient-years (PY) of TEAEs was 143.5, with an EAIR of 5.8 for serious TEAEs, 1.3 for serious infections, and 3.8 for Candida infections (Table 1). All Candida infections were mild or moderate; none were systemic or led to study discontinuation. Over 156 weeks, the EAIR of inflammatory bowel disease (1.2), anterior uveitis (0.8), and injection site reactions (0.5) remained low. Efficacy demonstrated at Week 48 in BE AGILE was maintained or improved up to Week 156 (Figure 1). Mean ASDAS improved from 3.9 at BE AGILE baseline to 2.0 and 1.8 at Weeks 48 and 156 respectively (by MI). At Week 156 in the NRI analyses, ASAS40 and ASAS PR were achieved by 62.6% (OC: 72.6%) and 32.7% (OC: 37.9%) patients respectively. ASDAS-ID and ASDAS 〈 2.1 responder rates (NRI) were maintained or continued to increase from Week 48, and by Week 156, responses were achieved by 28.0% (OC: 33.0%) and 57.1% (OC: 67.4%) patients respectively. ASDAS-MI responder rates (NRI) continued to increase from 44.9% at Week 48 to 46.5% at Week 156 (OC: 52.9%). Table 1. Safety for total exposure to BKZ across BE AGILE and the OLE BE AGILE Weeks 0–48 BE AGILE + OLE Weeks 0–156 n (%) [EAIR/100 PY] BKZ 160 mg (n=149; 114.2 PY ) BKZ 320 mg (n=150; 119.6 PY ) All BKZ (N=303; 261.3 PY ) All BKZ (N=303; 781.0 PY ) Any TEAE 103 (69.1) [168.7] 122 (81.3) [221.1] 235 (77.6) [186.2] 280 (92.4) [143.5] Serious TEAEs 5 (3.4) [4.4] 6 (4.0) [5.1] 13 (4.3) [5.1] 43 (14.2) [5.8] Key TEAEs of special monitoring Serious infections 3 (2.0) [2.7] 1 (0.7) [0.8] 4 (1.3) [1.5] 10 (3.3) [1.3] Candida infections 10 (6.7) [9.1] 9 (6.0) [7.9] 19 (6.3) [7.5] 28 (9.2) [3.8] Inflammatory bowel disease 1 (0.7) [0.9] 2 (1.3) [1.7] 4 (1.3) [1.5] 9 (3.0) [1.2] Anterior uveitis 1 (0.7) [0.9] 1 (0.7) [0.8] 2 (0.7) [0.8] 6 (2.0) [0.8] Study discontinuations due to TEAEs 7 (4.7) 10 (6.7) 20 (6.6) 38 (12.5) Drug-related TEAEs 48 (32.2) 54 (36.0) 110 (36.3) 149 (49.2) Deaths 1 (0.7) 0 1 (0.3) 2 (0.7) TEAEs are reported for the BE AGILE safety set for total exposure to BKZ across BE AGILE and the OLE. There was one death in BE AGILE (cardiac arrest) and one in the OLE (road traffic accident); neither was considered treatment-related. Conclusion: The safety profile of BKZ in patients with AS was in line with previous observations. 1.2 Patients treated with BKZ demonstrated sustained and consistent efficacy over 156 weeks. References: [1]van der Heijde D. Ann Rheum Dis 2020;79:595–604; 2. Baraliakos X. Arthritis Rheumatol 2020;72 (suppl 10). Acknowledgements: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical. Disclosure of Interests: Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Director of Imaging Rheumatology, Atul Deodhar Speakers bureau: Janssen, Novartis, Pfizer, Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB Pharma, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, UCB Pharma, Grant/research support from: Pfizer, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Novartis, Pfizer, Samsung Bioepis, UCB Pharma, Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Alan Kivitz Shareholder of: Pfizer, Novartis, Speakers bureau: Amgen, Eli Lilly, Pfizer, Novartis, Consultant of: Novartis, UCB Pharma, Maxime Dougados Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Marga Oortgiesen Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma

Abstract: Pain is a debilitating symptom of ankylosing spondylitis (AS) and negatively impacts patient (pt) lives. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, and tyrosine kinase 2, 1 showed significant efficacy vs placebo (PBO) in the randomized phase 2/3 SELECT-AXIS 1 study in active AS. 2 Objectives: To evaluate the efficacy of UPA on multiple pain assessments through 64 weeks (wks). Methods: SELECT-AXIS 1 ( NCT03178487 ) enrolled adults with active AS, who had an inadequate response, intolerance or contraindications to ≥2 NSAIDs, were biologic DMARD naive and met the modified New-York Criteria. Pts were randomized 1:1 to UPA 15 mg once daily (QD, n=93) or PBO (n=94) for 14 wks (Period 1), followed by open-label UPA 15 mg QD during 90-wk extension (Period 2); reported here are data through wk 64. Pain endpoints included the proportion of pts achieving ≥30%/≥50%/≥70% reduction in Pt’s Global Assessment (PGA) of pain on a 0–10 numeric rating scale (NRS), minimal clinically important difference (MCID, defined as ≥1 point reduction or ≥15% reduction from baseline [BL]) in PGA of pain, and much better improvement (MBI, defined as ≥2 point reduction and ≥33% reduction from BL) in PGA of pain. In addition, mean change from baseline in PGA of pain, BASDAI questions 2 (neck/back/hip pain) and 3 (peripheral pain/swelling), and pt’s assessment of back pain and nocturnal back pain NRS scores (NRS 0–10) were assessed. Non-responder imputation (binary endpoints) and mixed-effects model for repeated measurements (continuous endpoints) were used for missing data/dropouts in Period 1; as-observed analysis was used for Period 2. Results: A significantly higher proportion of pts receiving UPA vs PBO achieved reductions in all PGA of pain assessments as early as wk 2 that was sustained at all time points in Period 1; the only exception was ≥70% reduction in PGA of pain that was significant at wk 4 and sustained thereafter (Figure 1). For ≥30%/≥50%/≥70% reduction and MBI, the response rate increased over time with UPA; the difference for UPA vs PBO also continued to increase over time for ≥50% and ≥70% reduction endpoints. For MCID, an increase from BL to wk 2 was observed and plateaued thereafter. The mean change from BL in PGA of pain, BASDAI Q2, back pain, and nocturnal back pain NRS scores were significantly greater for UPA vs PBO at all time points in Period 1; BASDAI Q3 was significant at wk 8 and 14 (Figure 1). The effect of UPA on pain reduction was sustained through wk 64. PBO pts who switched to open-label UPA at wk 14 generally reached the same level of pain reduction as those initially randomized to UPA (Figure 1). Conclusion: In pts with active AS and an inadequate response/contraindication to NSAIDs, a greater proportion of patients treated with UPA achieved rapid, significant, and clinically meaningful reductions in pain vs PBO through 14 wks across multiple pain assessments. The reductions in pain were sustained over time, and pts who switched from PBO to UPA reached the same level of improvement as the continuous UPA group. References: [1]Parmentier JM, et al. BMC Rheumatology . 2018;2(23). [2]van der Heijde D, et al. Lancet . 2019;394(10214):2108-2117. 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 support was provided by M Hovenden and J Matsuura of ICON plc and was funded by AbbVie. Disclosure of Interests: Atul Deodhar Speakers bureau: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Consultant of: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Grant/research support from: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Xenofon Baraliakos Consultant of: Novartis, Pfizer AbbVie, Eli Lilly, UCB Pharma, Galapagos Janssen, Celgene and Amgen, Grant/research support from: Novartis, Pfizer AbbVie, Eli Lilly, UCB Pharma, Galapagos Janssen, Celgene and Amgen, Iain McInnes Consultant of: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB, Kurt de Vlam Speakers bureau: Celgene Eli Lilly, Galapagos, Novartis, and UCB, Consultant of: Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Grant/research support from: Celgene and Galapagos, Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, and Sanofi, Consultant of: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, Gilead, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, and Gilead, anna maniccia Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Christopher Saffore Shareholder of: AbbVie, Employee of: AbbVie, Tianming Gao Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie, Andrew Ostor Consultant of: AbbVie, BMS, Roche, Janssen, Lilly, Novartis, Pfizer, UCB, Gilead, and Paradigm