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POS0939 (2022)
BIMEKIZUMAB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 24-WEEK EFFICACY & SAFETY FROM BE MOBILE 1, A PHASE 3, MULTICENTRE, RANDOMISED, PLACEBO‑CONTROLLED STUDY
A. Deodhar1, D. Van der Heijde2, L. S. Gensler3, H. Xu4, K. Gaffney5, H. Dobashi6, W. P. Maksymowych7, M. Rudwaleit8, M. Magrey9, D. Elewaut10,11, M. Oortgiesen12, C. Fleurinck13, A. Ellis12, T. Vaux14, J. Smith14, X. Baraliakos15
1Oregon Health & Science University, Division of Arthritis & Rheumatic Diseases, Portland, United States of America
2Leiden University Medical Center, Department of Rheumatology, Leiden, Netherlands
3University of California San Francisco, Department of Rheumatology, San Francisco, United States of America
4Shanghai Changzheng Hospital, Affiliated to Second Military Medical University, Department of Rheumatology and Immunology, Shanghai, China
5Norfolk and Norwich University Hospital NHS Trust, Rheumatology Department, Norwich, United Kingdom
6Kagawa University, Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa, Japan
7University of Alberta, Department of Medicine, Alberta, Canada
8University of Bielefeld, Klinikum Bielefeld, Bielefeld, Germany
9Case Western Reserve University, MetroHealth Medical Center, Cleveland, United States of America
10Ghent University Hospital, Department of Rheumatology, Ghent, Belgium
11Ghent University, Center for Inflammation Research, Ghent, Belgium
12UCB Pharma, N/A, Raleigh, United States of America
13UCB Pharma, N/A, Brussels, Belgium
14UCB Pharma, N/A, Slough, United Kingdom
15Ruhr-University Bochum, Rheumazentrum Ruhrgebiet Herne, Bochum, Germany

Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits IL-17F in addition to IL-17A. BKZ has shown rapid and sustained efficacy and was well tolerated up to 156 weeks (wks) in a phase 2b study in patients (pts) with active ankylosing spondylitis. 1,2


Objectives: To assess efficacy and safety of BKZ vs placebo (PBO) in pts with active non-radiographic axial spondyloarthritis (nr-axSpA) up to Wk 24 in the ongoing pivotal phase 3 study, BE MOBILE 1.


Methods: BE MOBILE 1 (NCT03928704) comprises a 16-wk double-blind, PBO-controlled period and 36-wk maintenance period. Pts were aged ≥18 yrs, had BASDAI ≥4 and spinal pain ≥4 at BL, and sacroiliitis on MRI and/or elevated CRP at screening. Pts were randomised 1:1, BKZ 160 mg Q4W:PBO. From Wk 16, all pts received BKZ 160 mg Q4W. Primary and secondary efficacy endpoints were assessed at Wk 16.


Results: Of 254 randomised pts (BKZ: 128; PBO: 126), 244 (96.1%) completed Wk 16, 240 (94.5%) Wk 24. BL characteristics were comparable between groups: mean age 39.4 yrs, symptom duration 9.0 yrs; 54.3% pts male, 77.6% HLA-B27+, 10.6% TNFi-experienced. At Wk 16, the primary (ASAS40: 47.7% BKZ vs 21.4% PBO; p<0.001) and all ranked secondary endpoints were met ( Table 1 ). Responses were rapid with BKZ, including in PBO pts who switched to BKZ at Wk 16, and increased to Wk 24 ( Figure 1 ; Table 1 ). Substantial reductions of hs-CRP by Wk 2 and MRI SIJ inflammation by Wk 16 were achieved with BKZ vs PBO ( Table 1 ). At Wk 24, >50% of pts initially randomised to BKZ had achieved ASDAS <2.1 ( Figure 1 ).

Efficacy at Wks 16 and 24

BL Wk 16 Wk 24
PBO N=126 BKZ 160 mg Q4W N=128 PBO N=126 BKZ 160 mg Q4W N=128 p value PBO→BKZ 160 mg Q4W N=126 BKZ 160 mg Q4W N=128
Ranked endpoints in hierarchical order ASAS40 * [NRI] n (%) - - 27 (21.4) 61 (47.7) <0.001 59 (46.8) 67 (52.3)
BASDAI CfB † [MI] mean (SE) 6.7 (0.1) 6.9 (0.1) –1.5 (0.2) –3.1 (0.2) <0.001 –3.2 (0.2) –3.4 (0.2)
ASAS20 † [NRI] n (%) - - 48 (38.1) 88 (68.8) <0.001 87 (69.0) 96 (75.0)
ASAS PR † [NRI] n (%) - - 9 (7.1) 33 (25.8) <0.001 35 (27.8) 37 (28.9)
ASDAS-MI † [NRI] n (%) - - 9 (7.1) 35 (27.3) <0.001 37 (29.4) 41 (32.0)
ASAS 5/6 † [NRI] n (%) - - 21 (16.7) 49 (38.3) <0.001 51 (40.5) 57 (44.5)
BASFI CfB † [MI] mean (SE) 5.3 (0.2) 5.5 (0.2) –1.0 (0.2) –2.5 (0.2) <0.001 –2.3 (0.2) –2.8 (0.2)
Nocturnal spinal pain CfB † [MI] mean (SE) 6.7 (0.2) 6.9 (0.2) –1.7 (0.2) –3.6 (0.3) <0.001 –3.5 (0.2) –4.0 (0.3)
ASQoL CfB † [MI] mean (SE) 9.4 (0.4) 9.5 (0.4) –2.5 (0.4) –5.2 (0.4) <0.001 –4.8 (0.4) –5.7 (0.4)
SF-36 PCS CfB † [MI] mean (SE) 33.6 (0.8) 33.3 (0.7) 5.5 (0.7) 9.5 (0.7) <0.001 10.1 (0.8) 10.6 (0.8)
Other endpoints d Enthesitis-free state †a [NRI] n (%) - - 22 (23.9) b 48 (51.1) c - 40 (43.5) b 45 (47.9) c
ASAS40 in TNFi-experienced [NRI] n (%) - - 2 (11.8) e 6 (60.0) f - - -
ASDAS-CRP CfB [MI] mean (SE) 3.7 (0.1) 3.8 (0.1) –0.6 (0.1) –1.5 (0.1) - –1.5 (0.1) –1.6 (0.1)
hs-CRP, mg/L [MI] geometric mean (median) 5.0 (6.5) 4.6 (6.1) 3.8 (4.1) 2.0 (1.8) - 2.3 (2.6) 1.9 (1.8)
MRI spine Berlin CfB g [OC] mean (SD) 1.9 (3.2) h 1.6 (2.9) i –0.1 (1.7) j –0.7 (2.2) k - - -
SPARCC MRI SIJ score CfB g [OC] mean (SD) 10.5 (13.8) l 8.5 (10.3) m –1.5 (9.2) n –6.3 (10.0) o - - -

Randomised set. *Primary endpoint; † Secondary endpoint; a MASES=0 in pts with BL MASES >0; b n=92; c n=94; d Nominal p values not shown; e n=17; f n=10; g In pts in MRI sub-study; h n=65; i n=75; j n=58; k n=73; l n=68; m n=79; n n=60; o n=77.

Over 16 wks, 80/128 (62.5%) pts had ≥1 TEAE on BKZ vs 71/126 (56.3%) on PBO; most frequent were nasopharyngitis (BKZ: 9.4%; PBO: 4.8%), upper respiratory tract infection (BKZ: 7.0%; PBO: 7.1%) and oral candidiasis (BKZ: 3.1%; PBO: 0%). No systemic candidiasis was observed. Up to 16 wks, incidence of SAEs was low (BKZ: 0.0%; PBO: 0.8%); no MACE or deaths were reported; 0 IBD cases occurred in pts on BKZ vs 1 (0.8%) in a pt on PBO.


Conclusion: Dual inhibition of IL-17A and IL-17F with BKZ in pts with active nr-axSpA resulted in rapid, clinically relevant improvements in efficacy outcomes vs PBO. No new safety signals were observed. 1,2


REFERENCES:

[ 1]van der Heijde D. Ann Rheum Dis 2020;79:595–604;

[2]Gensler L. Arthritis Rheumatol 2021;73(suppl 10):0491.


Acknowledgements: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.


Disclosure of Interests: Atul Deodhar Speakers bureau: Janssen, Novartis, and Pfizer, Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Employee of: Imaging Rheumatology BV (Director), Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Novartis, Pfizer and UCB Pharma, Huji Xu: None declared, Karl Gaffney Speakers bureau: AbbVie, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Eli Lilly, Novartis, and UCB Pharma, Grant/research support from: AbbVie, Gilead, Eli Lilly, Novartis, and UCB Pharma, Hiroaki Dobashi Speakers bureau: BMS, Chugai, Eli Lilly, GSK, MSD, Novartis, Pfizer, UCB Pharma, Walter P Maksymowych Consultant of: AbbVie, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, Janssen, Novartis and Pfizer, Employee of: Chief Medical Officer for CARE Arthritis, Martin Rudwaleit Speakers bureau: AbbVie, BMS, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Paid instructor for: Janssen, Novartis, and UCB Pharma, Consultant of: AbbVie, Novartis, and UCB Pharma, Marina Magrey Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and UCB Pharma, Dirk Elewaut Speakers bureau: AbbVie, Eli Lilly, Galapagos, Novartis and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Galapagos, Novartis and UCB Pharma, Marga Oortgiesen Employee of: Employee of UCB Pharma, Carmen Fleurinck Employee of: Employee of UCB Pharma, Alicia Ellis Employee of: Employee of UCB Pharma, Thomas Vaux Employee of: Employee of UCB Pharma, julie smith Employee of: Employee of UCB Pharma, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB Pharma

Citation: , volume 81, supplement 1, year 2022, page 772
Session: Spondyloarthritis - treatment (POSTERS only)