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: The monoclonal antibody guselkumab (GUS; anti- IL-23p19-subunit) is approved to treat psoriatic arthritis (PsA). Post hoc analyses of DISCOVER-1 & 2 suggested that GUS may be effective in improving symptoms of axial manifestation of PsA. Objectives: Evaluate the efficacy of GUS across components of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in improving symptoms of axial manifestations of active PsA patients (pts) using data from Phase 3, randomized, placebo (PBO)-controlled studies. Methods: DISCOVER-1 & 2 enrolled pts with active PsA; pts were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W) or at Wk0, 4, and Q8W, or PBO. These post hoc analyses included pts who were identified by the investigator as having axial symptoms and sacroiliitis (prior X-ray or MRI or screening X-ray). BASDAI scores were assessed at Wks 0, 8, 16, 24, and 52. Mean BASDAI component scores through Wk52 are reported by treatment group. Pooled data from the two studies are reported. Mean BASDAI component scores are reported using observed data; total BASDAI scores with missing components were set to missing. The proportion of pts achieving ≥50% improvement in BASDAI (BASDAI 50) was also determined; pts with missing data or who met the treatment failure criteria (discontinued study agent or used prohibited medications) were considered nonresponders at all subsequent timepoints. Results: These analyses included 312 pts from DISCOVER-1 & 2 (103 GUS Q4W, 91 GUS Q8W, 118 PBO); mean total BASDAI scores at Wk0 were 6.4, 6.5, and 6.6, respectively. Demographics and mean baseline BASDAI component scores (ie, fatigue, spinal pain, joint pain, enthesitis, qualitative morning stiffness, and quantitative morning stiffness) were similar across treatment groups (Table 1). In comparison with the total study population, this subgroup of pts had a higher mean C-reactive protein level at baseline and a higher proportion of pts with enthesitis and included a slightly higher proportion of males. Mean scores for all six BASDAI components, including spinal pain, decreased through Wk24 in GUS-treated pts, with separation from PBO observed as early as Wk8; improvements were maintained at Wk52. At Wk24, BASDAI 50 response rates were higher in the Q4W and Q8W groups vs PBO (38% and 40% vs 19%). 1 At WK52, mean BASDAI component scores for PBO pts who crossed over to GUS Q4W at Wk24 were similar to those for pts who were randomized to GUS. 2 A similar trend was observed for BASDAI50 response. Conclusion: Among PsA pts with axial symptoms and sacroiliitis (via investigator-confirmed imaging) in the DISCOVER-1 & 2 trials, GUS treatment resulted in lower mean scores for all six BASDAI components compared with PBO as early as Wk 8 and through Wk24, with mean scores maintained at Wk52. References: [1]Helliwell P, et al. Ann Rheum Dis. 2020; 79; Suppl 1. [2]Mease PJ, et al. Arthritis Rheumatol. 2020; 72 (suppl 10). Table 1. Baseline demographic and disease characteristics for patients who were identified by physicians as having symptoms consistent with spondylitis and had sacroiliitis confirmed via prior radiograph/MRI or screening radiograph GUS Q4W GUS Q8W Placebo Patients, n 103 91 118 Male, n (%) 68 (66) 54 (59) 69 (59) Age, years 44.9 ± 11.8 45.0 ± 10.7 45.3 ± 11.0 BASDAI Patients, n 95 84 110 Score 6.4 ± 1.7 6.5 ± 1.8 6.6 ± 1.5 BASDAI Components Fatigue 6.4 ± 2.0 6.7 ± 1.9 6.5 ± 1.9 Spinal pain 6.6 ± 2.1 6.5 ± 2.3 6.7 ± 2.0 Joint pain 6.3 ± 1.9 6.5 ± 2.2 6.8 ± 1.7 Enthesitis 6.3 ± 2.1 6.4 ± 2.2 6.3 ± 2.2 Qualitative morning stiffness 6.8 ± 2.1 6.7 ± 2.5 7.0 ± 2.0 Quantitative morning stiffness 6.2 ± 2.9 5.7 ± 2.9 6.1 ± 2.8 Data are mean ± standard deviation unless otherwise noted. BASDAI, Bath ankylosing spondylitis disease activity index Disclosure of Interests: Frank Behrens Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene, Chugai, Janssen, Pfizer, and Roche, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: AbbVie, Janssen, Pfizer, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, Yanli Wang Employee of: IQVIA providing statistical support (funded by Janssen), Xenofon Baraliakos Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Abstract: Ixekizumab (IXE) has demonstrated clinical efficacy in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) together with significant repair of structural lesions in the sacroiliac joint (SIJ) on MRI. There is, however, a paucity of data as to which patients may be most responsive. Objectives We aimed to evaluate whether patients’ gender, HLA-B27 status, and presence of MRI inflammation impacted the effect of treatment with IXE versus placebo (PBO) on MRI structural lesions in the SIJ in patients with nr-axSpA. Methods Patients with active nr-axSpA, biologic-naïve (COAST-X, NCT02757352 ) were randomized 1:1:1 to ixekizumab 80 mg every 4 (Q4W) or 2 weeks (Q2W) or PBO. Structural lesions on SIJ MRI were assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ structural score (SSS). Treatment comparisons used analysis of covariance based on observed cases. SPARCC SSS subgroup analyses were performed according to baseline gender, HLA-B27 status, and SPARCC MRI SIJ bone marrow oedema (BME) 〈 4 and ≥4 subgroups, which reflects a definite MRI for inflammation in the SIJ typical of axSpA. Results Of 303 randomized patients, 266 patients (Q4W: n=85, Q2W: n=91, PBO: n=90) had an MRI scan at baseline and week 16. At baseline, SPARCC scores were consistently higher in males, and mostly higher in HLA-B27 and BME≥4 positive subgroups. Significant differences between patients treated with IXE versus PBO were observed for male patients, HLA-B27 positives, and those with baseline SPARCC BME ≥4. Numerically similar changes were observed in female patients, patients with negative HLA-B27, and patients with SPARCC BME 〈 4, though not statistically significant. Conclusion Effects of IXE on structural repair are most evident in males, HLA-B27 positives, and patients with definite MRI inflammation at baseline. Table 1. MRI SIJ Structural Lesion Outcomes. Lesion Analysis PBO IXE Q4W IXE Q2W Male (n=39) Female (n=51) Male (n=44) Female (n=41) Male (n=43) Female (n=48) Erosion BL mean 5·167 1·980 3·545 2·817 3·523 2·594 LS mean CFB (SE) 0·51 (0·20) -0·11 (0·17) -0·63 (0·18) -0·11 (0·19) -0·51 (0·18) -0·32 (0·17) P value vs PBO NA NA p 〈 0·001 p 〉 0·99 p 〈 0·001 p=0·37 Fat BL mean 2·051 0·912 2·091 1·293 1·465 0·677 LS mean CFB (SE) -0·02 (0·09) -0·03 (0·08) 0·29 (0·08) 0·03 (0·08) 0·21 (0·08) 0·04 (0·08) P value vs PBO NA NA p=0·01 p=0·65 p=0·062 p=0·51 Backfill BL mean 1·154 0·167 0·663 0·415 0·791 0·323 LS mean CFB (SE) -0·20 (0·13) 0·01 (0·11) 0·39 (0·12) 0·01 (0·12) 0·34 (0·12) 0·14 (0·11) P value vs PBO NA NA p 〈 0·001 p 〉 0·99 p=0·002 p=0·38 Lesion Analysis HLA-B27+ HLA-B27 - HLA-B27+ HLA-B27 - HLA-B27+ HLA-B27 - (n=64 ) (n=25 ) (n=61 ) (n=23 ) (n=65 ) (n=26 ) Erosion BL mean 3·820 2·100 3·467 2·543 3·515 1·827 LS mean CFB (SE) 0·27 (0·15) -0·10 (0·24) -0·49 (0·15) -0·01 (0·25) -0·50 (0·15) -0·17 (0·24) P value vs PBO NA NA p 〈 0·001 p=0·79 p 〈 0·001 p=0·84 Fat BL mean 1·578 1·020 1·328 2·783 1·285 0·462 LS mean CFB (SE) -0·06 (0·06) -0·06 (0·10) 0·22 (0·06) 0·01 (0·10) 0·13 (0·06) 0·10 (0·10) P value vs PBO NA NA p=0·002 p=0·65 p=0·027 p=0·25 Backfill BL mean 0·742 0·240 0·542 0·565 0·762 0 LS mean CFB (SE) -0·12 (0·10) 0·01 (0·16) 0·28 (0·10) 0 (0·17) 0·27 (0·10) 0·16 (0·16) P value vs PBO NA NA p=0·005 p=0·96 p=0·005 p=0·52 Lesion Analysis BME ≥4 BME 〈 4 BME ≥4 BME 〈 4 BME ≥4 BME 〈 4 (n=40 ) (n=50 ) (n=27 ) (n=58 ) (n=38 ) (n=53 ) Erosion BL mean 4·863 2·160 5·352 2·190 5·276 1·425 LS mean CFB (SE) 0·42 (0·19) -0·06 (0·17) -0·70 (0·23) -0·23 (0·16) -0·71 (0·20) -0·19 (0·17) P value vs PBO NA NA p 〈 0·001 p=0·47 p 〈 0·001 p=0·57 Fat BL mean 0·775 1·910 1·926 1·603 1·671 0·604 LS mean CFB (SE) -0·02 (0·08) -0·02 (0·07) 0·54 (0·10) -0·01 (0·07) 0·28 (0·08) 0·01 (0·07) P value vs PBO NA NA p 〈 0·001 p=0·90 p=0·013 p=0·74 Backfill BL mean 0·750 0·470 1·019 0·328 0·763 0·387 LS mean CFB (SE) -0·21 (0·12) 0·01 (0·11) 0·41 (0·15) 0·11 (0·10) 0·49 (0·13) 0·05 (0·11) P value vs PBO NA NA p=0·002 p=0·52 p 〈 0·001 p=0·80 CFB=change from BL. BL=baseline, LS=least squares. Acknowledgements Study was sponsored by Eli Lilly and Company Disclosure of Interests Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer, and UCB and is Chief Medical Officer of CARE Arthritis Ltd, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Xenofon Baraliakos Grant/research support from: Abbvie, Amgen, BMS, Chugai, Galapagos, Gilead, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB, Robert G Lambert Consultant of: CARE Arthritis, Image Analysis Group, Parexel, and Pfizer, Robert B.M. Landewé Consultant of: AbbVie, Astra-Zeneca, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Gilead, Galapagos, Glaxo-Smith-Kline, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB; and is director of Imaging Rheumatology BV, which is a registered company under Dutch Law, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Hilde Carlier Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jeffrey Lisse 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, Maja Hojnik Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly and Company, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly and Company, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Grant/research support from: AbbVie, BMS, Merck, Celgene, and Novartis

Abstract: It is important to understand the potential effect long-term therapy with biologics can have on structural changes in the spine among patients with active radiographic axial spondyloarthritis (r-axSpA, ankylosing spondylitis). Objectives: We examined radiographic progression in the spine among patients with active r-axSpA treated with ixekizumab, an IL-17A antagonist, for 2 years, and potential predictors of spinal radiographic progression. Methods: Patients with active r-axSpA, biologic-naive (COAST-V, NCT02696785 ) or with prior experience with a maximum of 2 TNF inhibitors (COAST-W, NCT02696798 ), received 80 mg ixekizumab every 2 or 4 weeks for 2 years (108 weeks, of which 56 weeks were the COAST-Y extension study, NCT03129100 ). Mean change from baseline of modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (average score from 2 selected readers, blinded for time order) for patients treated with ixekizumab for 2 years with data at both baseline and year 2 is presented (N=230; 54% of total randomized patients). Non-progression is presented for all patients and subgroups based on TNFi-experience. Predictors were identified in multivariate logistic regression models with stepwise selection criteria of p-value 〈 0.1. All data are observed. Results: At baseline, patients (N=230) were predominately male (82%) with an average age of 43 years, mean symptom duration of 16 years, 52% were TNFi-experienced, mean (SD) ASDAS score was 4.0 (0.7), most were HLA-B27 positive (87%) and 40% had syndesmophytes (identified by both selected readers at the same location). Baseline mSASSS (SD) was 11.0 (16.3) and change from baseline at year 2 of treatment was 0.3 (1.8) (Table 1). The proportion of non-progressors (mSASSS change from baseline 〈 2) over 2 years was 89.6% (total IXE [all patients]), 90.9% (biologic-naive) and 88.3% (TNFi-experienced), and, if defined as mSASSS change from baseline ≤0, 75.7% (total IXE [all patients] ), 78.2% (biologic-naive) and 73.3% (TNFi-experienced) (Table 1). Predictors of structural progression at year 2 (mSASSS change 〉 0) were age, baseline syndesmophytes, HLA-B27 status and gender (Table 1). Week 52 inflammation in MRI SPARCC spine was also identified as a predictor for structural progression at year 2 in a separate model for patients from COAST-V where MRI measures were available at baseline and Week 52 (N=109). Conclusion: The majority of patients treated with ixekizumab for 2 years did not show radiographic progression, and the overall mean progression was low. Similar levels of non-progression were observed in biologic-naive patients and patients previously exposed to TNFis. Predictors were generally consistent with previous studies. Table 1. Spinal radiographic changes for patients with active r-axSpA treated with ixekizumab for 2 years Change in mSASSS at year 2 All patients a N=230 Biologic-naive N=110 TNFi-experienced N=120 Baseline mSASSS, mean (SD) 11.0 (16.3) 10.1 (15.5) 11.7 (17.0) Change at year 2, mean (SD) 0.3 (1.8) 0.3 (2.0) 0.4 (1.6) Change in total mSASSS 〈 2, n (%) 206 (89.6) 100 (90.9) 106 (88.3) Change in total mSASSS ≤0, n (%) 174 (75.7) 86 (78.2) 88 (73.3) Multivariable logistic regression model Prediction for change in total mSASSS 〉 0, OR (95% CI), p-value All patients a,b N=228 Age (≥40 years vs. 〈 40 years) 2.97 (1.41, 6.28) p=0.004 c Baseline syndesmophytes b (yes vs. no) 2.31 (1.18, 4.54) p=0.015 c Baseline HLA-B27 (positive vs. negative) 3.78 (1.04, 13.75) p=0.044 c Gender (male vs. female) 3.16 (1.01, 9.86) p=0.047 c Baseline ASDAS state ( 〉 3.5 vs. [2.1, 3.5]) 2.26 (0.96, 5.34) p=0.063 a Combined ixekizumab group of Q2W and Q4W patients with baseline and year-2 mSASSS data b Identified by both selected readers at the same location (2 patients were not evaluable by both readers) c p 〈 0.05 Abbreviations: ASDAS=Assessment of Disease Activity, CI=confidence interval, IXE=ixekizumab, mSASSS=modified Stoke Ankylosing Spondylitis Spinal Score, OR=odds ratio, Q2W=every 2 weeks, Q4W=every 4 weeks, SD=standard deviation, TNFi=tumor necrosis factor inhibitor 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, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Director of Imaging Rheumatology bv., Mikkel Østergaard Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Eli Lilly and Company, Janssen, Merck, Pfizer, Roche, UCB, Celgene, Sanofi, Regeneron, Novartis, Grant/research support from: AbbVie, BMS, Merck, UCB, Celgene, Novartis, John D Reveille Paid instructor for: UCB, Eli Lilly and Company, Consultant of: UCB, Eli Lilly and Company, Pfizer, Novartis, Grant/research support from: Janssen, Eli Lilly and Company, Xenofon Baraliakos Speakers bureau: Abbvie, BMS, Lilly, Janssen, Novartis, MSD, Pfizer, Galapagos, Gilead, UCB, Paid instructor for: Abbvie, BMS, Lilly, Janssen, Novartis, MSD, Pfizer, Galapagos, Gilead, UCB, Consultant of: Abbvie, BMS, Lilly, Janssen, Novartis, MSD, Pfizer, Galapagos, Gilead, UCB, Andris Kronbergs 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, Hilde Carlier Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Adams Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Boehringer, BMS, Eli Lilly and Company, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer

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.