E089 Effect of secukinumab on radiographic progression and inflammation in sacroiliac joints and spine in patients with non-radiographic axial spondyloarthritis: 2-year imaging outcomes from a Phase III randomised trial
Authors: Marzo-Ortega Helena , Braun Juergen , Blanco Ricardo , Gensler Lianne S , van den Bosch Filip , Hall Stephen , Kameda Hideto , Poddubnyy Denis , van de Sande Marleen G H , van der Heidje Désirée , Zhuang Tingting , Stefanska Anna , Readie Aimee , Richards Hanno , Deodhar Atul 
Published: April 2023

Abstract

Background/Aims
In PREVENT (NCT02696031), secukinumab decreased sacroiliac joints (SIJ) bone marrow oedema (BMO) in patients with non-radiographic axial spondyloarthritis (nr-axSpA) through 52 weeks. We report radiographic progression and inflammation (BMO) assessed by X-ray and magnetic resonance imaging (MRI) of SIJ and spine over 2 years in PREVENT.

Methods
Patients (N = 555) were randomised (1:1:1) to secukinumab 150 mg, with loading dose (LD) or without (NL), or placebo. Switching to open-label secukinumab or standard of care (SoC) was permitted after Week (W) 20. By W52, all patients received open-label secukinumab or SoC. SIJ and spinal radiographs were collected at baseline and W104 and SIJ and spinal MR scans at baseline, W16, W52 and W104. Spinal radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and SIJ radiographs using modified New York criteria (mNYC). SIJ and spinal BMO was assessed using Berlin Active Inflammatory Lesions Scoring and Berlin MRI scoring, respectively. Average scores of two blinded central readers were used. W104 reading data are presented as observed.

Results
Radiographs showed most patients (88% secukinumab, 86% placebo) had no SIJ progression (defined as change ≤ smallest detectable change [SDC, 0.46] in total mNYC score) by W104; no patient had an increase ≥2. At W104, screening radiographs of eligible patients were re-evaluated alongside post-baseline images; ∼25% of screening radiographs (68/277 secukinumab; 34/139 placebo) were re-evaluated as mNYC-positive by &gt; 1 reader. Of these, 11/68 patients in the secukinumab (16.2%) and 5/34 in the placebo (14.7%) groups were evaluated as mNYC-negative at W104. Most patients who were mNYC-negative at screening remained mNYC-negative through W104 (202 secukinumab [96.7%]; 102 placebo [97.1%]). Almost all patients (98%) treated with secukinumab 150 mg (pooled LD and NL) showed no structural progression (change in total mSASSS ≤ SDC, [80% agreement level] of 0.76 over 2 years. At baseline, 62 patients (43 secukinumab, 19 placebo) presented with ≥1 syndesmophyte (≥1 vertebral unit scored by ≥ 1 reader). Of those 16 (9 secukinumab [20.9%]; 7 placebo [36.8%]) developed ≥1 new syndesmophyte by W104. Whilst of 354 patients (237 secukinumab, 117 placebo) without syndesmophytes at baseline, only 8 (4 secukinumab [1.7%]; 4 placebo [3.4%]) developed ≥1 new syndesmophyte by W104. Secukinumab reduced SIJ BMO score at W16 (-1.2) and W52 (-1.5) with sustained reduction through W104 (-1.7) in the overall population; greater reduction was observed in patients with baseline score &gt;2 (W16, -4.0; W52, -4.7; W104, -5.4). Baseline spinal inflammation on MRI was low (mean Berlin score: 0.82, secukinumab; 1.07, placebo) with no meaningful change up to W104 (0.56, secukinumab).

Conclusion
Most patients showed no radiographic progression through 2 years. There was some discrepancy between SIJ eligibility and efficacy reads. Secukinumab reduced SIJ inflammation (BMO) on MRI in patients with active nr-axSpA.
Disclosure
H. Marzo-Ortega: Consultancies; H.M.O. has received consultancy fees from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB. Member of speakers’ bureau; H.M.O. has received speakers bureau fees from AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda and UCB. Grants/research support; H.M.O. has received grant/research support from Janssen, Novartis and UCB. J. Braun: Consultancies; J.B. has received consultancy fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. Member of speakers’ bureau; J.B. has received speakers bureau fees from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. Grants/research support; J.B. has received grant/research support from AbbVie (Abbott), Amgen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Centocor, Chugai, Eli Lilly, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB. R. Blanco: Member of speakers’ bureau; R.B. has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MSD, Pfizer, Roche and UCB. Grants/research support; R.B. has received grant/research support from AbbVie, MSD and Roche. L.S. Gensler: Consultancies; L.S.G. has received consultancy fees from AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer and UCB. Grants/research support; L.S.G. has received grant/research support from Janssen, Novartis and UCB. F. van den Bosch: Consultancies; F.v.d.B. has received consultancy fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. Member of speakers’ bureau; F.v.d.B. has received speakers bureau fees from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. Grants/research support; F.v.d.B. has received grant/research support from AbbVie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer and UCB. S. Hall: Member of speakers’ bureau; S.H. has received speakers bureau fees from Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB; consultancy fees from Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB. Grants/research support; S.H. has received and grant/research support from AbbVie, Janssen, Merck and UCB. H. Kameda: Consultancies; H.K. has received consultancy fees from AbbVie, Eli Lilly, Gilead Sciences, Janssen, Novartis, Pfizer, Sanofi, Taisho and UCB. Member of speakers’ bureau; H.K. has received speakers bureau fees from AbbVie, Asahi-Kasei, AstraZeneca, Boehringer Ingelheim, BMS, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis and Pfizer. Grants/research support; H.K. has received grant/research support from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Eisai, Mitsubishi Tanabe and Taisho. D. Poddubnyy: Consultancies; D.P. has received consultancy fees from AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis and UCB. Member of speakers’ bureau; D.P. has received speakers bureau fees from AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer and UCB. Grants/research support; D.P. has received grant/research support from AbbVie, Eli Lilly, MSD, Novartis and Pfizer. M.G.H. van de Sande: Consultancies; M.G.H.v.d.S. has received consultancy fees from AbbVie, Eli Lilly, Novartis and UCB. Member of speakers’ bureau; M.G.H.v.d.S. has received speakers bureau fees from Novartis and UCB. Grants/research support; M.G.H.v.d.S. has received grant/research support from Eli Lilly, Janssen, Novartis and UCB. D. van der Heidje: Other; D.v.d.H. has worked as a paid instructor for AbbVie, Bayer, BMS, Cyxone, Eisai, Eli Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Novartis, Pfizer and UCB; and as a Director of Imaging Rheumatology at BV. T. Zhuang: Shareholder/stock ownership; T.Z. is a shareholder of Novartis. Other; T.Z. is an employee of Novartis. A. Stefanska: Shareholder/stock ownership; A.S. is a shareholder of Novartis. Other; A.S. is an employee of Novartis. A. Readie: Shareholder/stock ownership; A.R. is a shareholder of Novartis. Other; A.R. is an employee of Novartis. H. Richards: Shareholder/stock ownership; H.R. is a shareholder of Novartis. Other; H.R. is an employee of Novartis. A. Deodhar: Consultancies; A.D. has received consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer and UCB. Member of speakers’ bureau; A. D. has received speakers bureau fees from AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer and UCB. Grants/research support; A.D. has received grant/research support from AbbVie, Eli Lilly, GSK, Novartis, Pfizer and UCB.