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 Randomized Trial

BackgroundAxial spondyloarthritis (axSpA) is characterised by inflammation of the sacroiliac joints (SIJ) and the spine. Secukinumab (SEC) treatment was clinically efficacious and reduced SIJ bone marrow oedema as detected by magnetic resonance imaging (MRI) in patients (pts) with non-radiographic (nr)-axSpA through 52 weeks in the PREVENT (NCT02696031) study.1ObjectivesTo report radiographic progression and the course of inflammation as assessed by X-ray and MRI of SIJ and spine over 2 years in the PREVENT study.MethodsStudy design and key endpoints have been reported earlier.1 In total, 555 pts were randomised (1:1:1) to receive SEC 150 mg, with (LD) or without loading (NL) doses, or placebo (PBO). Switch to open-label (OL) SEC or standard of care (SoC) was permitted after Week (Wk) 20. All pts (except those who switched to SoC) received OL SEC from Wk 52. Radiographs of the spine and SIJ were collected at baseline (BL) and Wk 104; MR images of the spine and SIJ were collected at BL, Wk 16, 52, and 104. Spinal radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and SIJ radiographs according to modified New York criteria (mNYC). Pts whose screening SI joint radiographs fulfilled mNY criteria during the eligibility reading session were excluded from the study. Spinal MR images were assessed for signs of inflammation with the Berlin score. SIJ bone marrow oedema was assessed according to the Berlin Active Inflammatory Lesions Scoring. All images were evaluated in blinded fashion independently by 2 central readers. All data are reported from the Wk 104 reading session and are presented as observed.ResultsThe vast majority (98%) of pts treated with SEC 150 mg (pooled LD and NL) showed no structural progression, defined as change in total mSASSS score ≤ smallest detectable change (SDC) of 0.76 (80% agreement level) over 2 years. At BL, 62 pts (43 in SEC, 19 in PBO) presented with ≥1 syndesmophyte (≥1 vertebral unit scored by ≥1 reader). Among these pts, 9 in SEC (20.9%) and 7 in PBO (36.8%) groups had developed ≥1 new syndesmophyte by Wk 104. Among 237 SEC and 117 PBO pts without syndesmophytes at BL, only 4 pts on SEC (1.7%) and 4 pts on PBO (3.4%) developed ≥1 new syndesmophyte by Wk 104. SIJ radiographs showed that 88% of pts on SEC and 86% on PBO had no progression in SIJ (defined as change ≤ SDC (0.46) in total mNYC score) by Wk 104. No patient had an increase in total mNYC score of 2 or more. When screening radiographs of eligible pts were scored alongside post-BL images in the final reading campaign, approximately 25% of pts (68/277 and 34/139 pts in the SEC and PBO groups, respectively) were evaluated as mNY-positive at screening (pts were considered mNY-positive if ≥1 reader evaluated them as mNY-positive). Of these, 11/68 pts in the SEC (16.2%) and 5/34 in the PBO (14.7%) groups were evaluated as mNY-negative at Wk 104. In the SEC and PBO groups, 202 (96.7%) and 102 (97.1%) pts who were mNY-negative at screening stayed negative through Wk 104, respectively. Only 7 pts in the SEC (3.3%) and 3 in the PBO (2.9%) groups who were mNY-negative at BL were scored as mNY-positive at Wk 104. In both groups, fewer pts progressed from mNY-negative to mNY-positive than had a change in the opposite direction (from positive to negative), resulting in an overall negative net progression. Spinal inflammation on MRI (Berlin score) was low at BL with a mean of 0.82 in SEC and 1.07 in PBO groups with no meaningful change up to Wk 104 (mean of 0.56, SEC). SEC reduced SIJ bone marrow oedema score versus PBO at Wk 16 and Wk 52 with sustained reduction through Wk 104 in the overall patient population, with greater reduction in pts with BL score >2 (Figure 1).ConclusionMost pts initially randomised to SEC or PBO showed no radiographic progression through 2 years. There was some discrepancy between SIJ eligibility and efficacy reads. SEC reduced SIJ inflammation (bone marrow oedema) on MRI in pts with active nr-axSpA.References[1]Deodhar A, et al. Arthritis Rheumatol. 2021;73:110–20.Disclosure of InterestsJuergen Braun Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB pharma, Eli Lilly, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Eli Lilly, Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Eli Lilly, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD, Eli Lilly, Consultant of: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD, Grant/research support from: AbbVie, MSD, Roche, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Takeda, UCB, Consultant of: AbbVie, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Takeda, UCB, Grant/research support from: Janssen, Novartis, UCB, Lianne S. Gensler Consultant of: Gilead, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Grant/research support from: UCB, Pfizer, Filip van den Bosch Speakers bureau: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Stephen Hall Speakers bureau: Novartis, Merck, Janssen, Pfizer, Eli Lilly, UCB, Consultant of: Novartis, Merck, Janssen, Pfizer, Eli Lilly, UCB, Grant/research support from: AbbVie, UCB, Janssen, Merck, Hideto Kameda Speakers bureau: Abbvie, Asahi-Kasei, Astellas, BMS, Chugai, Eisai, Eli Lilly, Gilead Sciences, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Consultant of: Abbvie, Astellas, Boehringer, Eli Lilly, Gilead Sciences, Janssen, Novartis, Sanofi, UCB, Grant/research support from: Abbvie, Asahi-Kasei, Boehringer, Chugai, Eisai, Mitsubishi-Tanabe, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis, UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, Marleen G.H. van de Sande Speakers bureau: Novartis, MSD, Consultant of: Abbvie, Novartis, Eli Lily, Grant/research support from: Novartis, Eli Lilly, Janssen, UCB, Désirée van der Heijde Paid instructor for: Novartis, AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Pfizer, UCB Pharma, and Director of Imaging Rheumatology BV, Tingting Zhuang Shareholder of: Novartis, Employee of: Novartis, Anna Stefanska Shareholder of: Novartis, Employee of: Novartis, Aimee Readie Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis, Employee of: Novartis, Atul Deodhar Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB