L15: Effect of Secukinumab versus Adalimumab Biosimilar on Radiographic Progression in Patients with Radiographic Axial Spondyloarthritis: A Randomized Phase IIIb Study
Xenofon Baraliakos1, Mikkel Østergaard2, Denis Poddubnyy3, Désirée van der Heijde4, Atul Deodhar5, Pedro M. Machado6, Victoria Navarro-Compán7, Kay Geert Hermann8, Mitsumasa Kishimoto9, Eun Young Lee10, Lianne S Gensler11, Uta Kiltz1, Marco Eigenmann12, Patricia Pertel13, Aimee Readie14, Hanno B. Richards12, Brian Porter15 and Juergen Braun1, 1Rheumazentrum Ruhrgebiet, Herne, Ruhr-Universität Bochum, Bochum, Nordrhein-Westfalen, Germany, 2Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, 3Charité - Universitätsmedizin Berlin and German Rheumatism Research Centre, Berlin, Germany, 4Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 5Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, 6Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, United Kingdom, 7Department of Rheumatology, University Hospital La Paz, IdiPaz, Madrid, Spain, 8Department of Radiology, University Hospital Charité - Campus Mitte, Charitéplatz, Berlin, Germany, 9Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan, 10Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea, 11Department of Medicine, Division of Rheumatology, University of California San Francisco, San Francisco, CA, 12Novartis Pharma AG, Basel, Switzerland, 13Novartis Pharma AG, Reinach, Switzerland, 14Novartis Pharmaceuticals Corporation, East Hanover, NJ, 15Novartis Pharmaceuticals Corporation, Far Hills, NJ
Background/Purpose: Biologics are clinically efficacious in patients (pts) with axial spondyloarthritis (axSpA) including radiographic axSpA (r-axSpA). Limited data exist on the effect of biologics in slowing radiographic progression in pts with r-axSpA. Two-year data from MEASURE 1 showed low radiographic progression with secukinumab (SEC).1 We report data from SURPASS,2 the first head-to-head study in r-axSpA, that compared the effect of SEC vs adalimumab biosimilar (SDZ-ADL) on spinal radiographic progression.
Methods: In this phase IIIb study, bio-naïve pts with active r-axSpA with a Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) ≥4, spinal pain score ≥4 (range 0–10), total back pain score ≥40 mm (range 0–100 mm), and with high-sensitivity C-reactive protein (hs-CRP) ≥5 mg/L or ≥1 syndesmophyte(s) on spinal radiograph were randomized (1:1:1) to SEC (150/300 mg; dose-blinded) or SDZ-ADL (40 mg; open label). Radiographs and MRIs were reviewed by 3 independent central readers blinded to treatment arm and chronology of images. Primary endpoint was the proportion of pts with no radiographic progression (change from baseline [CFB] in modified Stoke AS Spinal Score [mSASSS] ≤0.5; mean score of readers) on SEC vs SDZ-ADL at week (wk) 104 (superiority testing). Secondary endpoints included CFB-mSASSS by wk 104, proportion of pts with ≥1 syndesmophyte(s) at baseline (BSL) with no new syndesmophytes(s) at wk 104, CFB-MRI Berlin sacroiliac joint (SIJ) inflammation score, CFB-AS spine MRI-activity (ASspiMRI-a) Berlin modification score, and safety.
Results: Overall, 859 pts received SEC 150 mg (n=287), 300 mg (n=286), or SDZ-ADL (n=286). Pt demographics and BSL disease characteristics were balanced. With 78.5% male, mean age 42.1 years, mSASSS 16.6, BASDAI 7.1, hsCRP 20.4 mg/L, and 73% with ≥1 syndesmophyte(s), this population had a high risk of radiographic progression. Mean BSL MRI edema scores were 1.6 to 2.5 for SIJ and 2.6 to 3.4 for spine. At wk 104, the proportion of pts with no radiographic progression (CFB-mSASSS ≤0.5) was 66.1%, 66.9%, and 65.6% in SEC 150 mg, 300 mg, and SDZ-ADL arms, respectively (Table 1; P=ns, both SEC doses). Mean CFB-mSASSS was 0.54, 0.55, and 0.72 in SEC 150 mg, 300 mg, and SDZ-ADL arms, respectively (Table 1). Similar rates of CFB-mSASSS were observed across arms (Figure 1). Overall, 56.9%, 53.8%, and 53.3% of pts in SEC 150 mg, 300 mg, and SDZ-ADL arms, respectively, with a BSL ≥1 syndesmophyte(s) did not develop new syndesmophyte(s) by wk 104 (Table 2). At wk 16, mean (SE) CFB-MRI SIJ scores were −1.22 (0.14), −1.10 (0.14), and −1.51 (0.14), and mean CFB-MRI spine scores were −1.43 (0.14), −1.59 (0.15), −2.31 (0.15) in SEC 150 mg, 300 mg, and SDZ-ADL arms, respectively. Overall, 79.7%, 81.8%, and 84.2% pts had ≥1 adverse event (AE), and 14.0%, 10.2%, and 11.2% pts had serious AEs in SEC 150 mg, 300 mg, and SDZ-ADL arms, respectively.
Conclusion: Spinal radiographic progression over 2 years was low with no significant difference between SEC and SDZ-ADL arms. Safety was consistent with the well-established safety profiles of SEC and SDZ-ADL.
References
Braun J et al. Ann Rheum Dis. 2017;76(6):1070-77
Baraliakos X et al. Clin Drug Investig. 2020;40(3):269-78
Disclosures: X. Baraliakos, Novartis, Bristol Myers Squibb, Chugai, MSD, Pfizer, UCB Pharma, AbbVie, Eli Lilly, Galapagos, Gilead, Celgene; M. Østergaard, AbbVie, Amgen Inc., Bristol-Myers Squibb(BMS), Merck/MSD, Celgene, Novartis, Boehringer-Ingelheim, Eli-Lilly, Galapagos, Gilead, Hospira, Janssen, MEDAC, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB; D. Poddubnyy, AbbVie, Biocad, Bristol Myers Squibb, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, UCB; D. van der Heijde, AbbVie, Bayer, Bristol Myers Squibb, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer, UCB Pharma, Imaging Rheumatology BV; A. Deodhar, AbbVie, Bristol Myers Squibb, Celgene, GSK, Eli Lilly, Novartis, Pfizer, UCB Pharma, Amgen, Aurinia, Janssen, MoonLake; P. Machado, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Eli Lilly, Celgene, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche, UCB; V. Navarro-Compán, AbbVie, Bristol-Myers Squibb(BMS), Eli Lilly, Galapagos, Janssen, MoonLake, MSD, Novartis, Pfizer, Roche, UCB; K. Hermann, AbbVie, Novartis, MSD, Pfizer, BerlinFlame GmbH; M. Kishimoto, AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, UCB, Celgene, Kyowa Kirin; E. Lee, Immunoforge, IMbiologics; L. Gensler, AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer, UCB Pharma; U. Kiltz, AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Grünenthal, GlaxoSmithKlein(GSK), Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB; M. Eigenmann, Novartis; P. Pertel, Novartis; A. Readie, Novartis; H. Richards, Novartis; B. Porter, Novartis; J. Braun, AbbVie/Abbott, Amgen, Bristol-Myers Squibb(BMS), Boehringer, Celgene, Novartis, Pfizer, Roche, UCB, Eli Lilly, Chugai, Celltrion, Medac, Sanofi.
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