Two-year imaging outcomes from a phase 3 randomized trial of secukinumab in patients with non-radiographic axial spondyloarthritis

(2023) 25:80 Braun et al. Arthritis Research & Therapy https://doi.org/10.1186/s13075-023-03051-5 Arthritis Research & Therapy Open Access RESEARCH Two‑year imaging outcomes from a phase 3 randomized trial of secukinumab in patients with non‑radiographic axial spondyloarthritis Juergen Braun1,2*, Ricardo Blanco3, Helena Marzo‑Ortega4, Lianne S. Gensler5, Filip Van den Bosch6,7, Stephen Hall8, Hideto Kameda9, Denis Poddubnyy10, Marleen van de Sande11, Désirée van der Heijde12, Tingting Zhuang13, Anna Stefanska14, Aimee Readie13, Hanno B. Richards15 and Atul Deodhar16 Abstract Background Radiographic progression and course of inflammation over 2 years in patients with non-radiographic axial spondyloarthritis (nr-axSpA) from the phase 3, randomized, PREVENT study are reported here. Methods In the PREVENT study, adult patients fulfilling the Assessment of SpondyloArthritis International Society classification criteria for nr-axSpA with elevated CRP and/or MRI inflammation received secukinumab 150 mg or pla‑ cebo. All patients received open-label secukinumab from week 52 onward. Sacroiliac (SI) joint and spinal radiographs were scored using the modified New York (mNY) grading (total sacroiliitis score; range, 0–8) and modified Stoke Anky‑ losing Spondylitis Spine Score (mSASSS; range, 0–72), respectively. SI joint bone marrow edema (BME) was assessed using the Berlin Active Inflammatory Lesions Scoring (0–24) and spinal MRI using the Berlin modification of the AS spine MRI (ASspiMRI) scoring (0–69). Results Overall, 78.9% (438/555) of patients completed week 104 of the study. Over 2 years, minimal changes were observed in total radiographic SI joint scores (mean [SD] change, − 0.04 [0.49] and 0.04 [0.36]) and mSASSS scores (0.04 [0.47] and 0.07 [0.36]) in the secukinumab and placebo-secukinumab groups. Most of the patients showed no structural progression (increase ≤ smallest detectable change) in SI joint score (87.7% and 85.6%) and mSASSS score (97.5% and 97.1%) in the secukinumab and placebo-secukinumab groups. Only 3.3% (n = 7) and 2.9% (n = 3) of patients in the secukinumab and placebo-secukinumab groups, respectively, who were mNYnegative at baseline were scored as mNY-positive at week 104. Overall, 1.7% and 3.4% of patients with no syn‑ desmophytes at baseline in the secukinumab and placebo-secukinumab group, respectively, developed ≥ 1 new syndesmophyte over 2 years. Reduction in SI joint BME observed at week 16 with secukinumab (mean [SD], − 1.23 [2.81] vs − 0.37 [1.90] with placebo) was sustained through week 104 (− 1.73 [3.49]). Spinal inflammation on MRI was low at baseline (mean score, 0.82 and 1.07 in the secukinumab and placebo groups, respectively) and remained low (mean score, 0.56 at week 104). Conclusion Structural damage was low at baseline and most patients showed no radiographic progression in SI joints and spine over 2 years in the secukinumab and placebo-secukinumab groups. Secukinumab reduced SI joint inflammation, which was sustained over 2 years. *Correspondence: Juergen Braun Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Braun et al. Arthritis Research & Therapy (2023) 25:80 Page 2 of 12 Trial registration ClinicalTrials.gov, NCT02696031. Keywords Axial spondyloarthritis, Non-radiographic axial spondyloarthritis, Nr-axSpA, Secukinumab, X-ray, Radiograph, Imaging Background Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the axial skeleton predominantly affecting the spine and sacroiliac (SI) joints [1]. Based on the presence or absence of definite structural changes in the SI joints on conventional radiographs, patients with axSpA are classified into 2 subtypes [2]. Patients with radiographic evidence of sacroiliitis fulfilling the modified New York (mNY) criteria are classified as having radiographic axSpA (r-axSpA, also known as ankylosing spondylitis [AS]) whereas patients who do not meet the mNY criteria but may show evidence of sacroiliitis on magnetic resonance imaging (MRI) are classified as having nonradiographic axSpA (nr-axSpA) [2–5]. Patients with nraxSpA have largely similar levels of disease activity, pain, and health-related quality of life impairment as patients with r-axSpA [6, 7]. It has been reported that about 10 to 40% of patients with nr-axSpA progress to r-axSpA over a period of 2 to 10 years [8]. The key goals of the treatment of axSpA include improving symptoms, decreasing inflammation, improving function and quality of life, and preventing irreversible skeletal damage, e.g., new bone formation in the spine [9]. Secukinumab, a human monoclonal immunoglobulin (IgG1) antibody that selectively neutralizes human interleukin (IL)-17A, demonstrated rapid and sustained improvement in the signs and symptoms of AS in longterm treatment (up to 5 years) in the phase 3 MEASURE studies [10–13]. PREVENT was the first randomized placebo-controlled phase 3 study to evaluate the efficacy and safety of secukinumab in patients with nr-axSpA with objective signs of inflammation [14]. Secukinumab improved signs and symptoms throughout the study period. The primary endpoint of 40% improvement in the Assessment of SpondyloArthritis International Society (ASAS40) criteria was met [14]. Radiographic progression and the course of inflammation as assessed by conventional radiographs and magnetic resonance imaging (MRI) of SI joint and spine, over 2 years from the PREVENT study, are reported here. Methods Study design and patients Study design and eligibility criteria have been reported previously in detail [14]. Briefly, PREVENT (NCT02696031) was a randomized, double-blind, placebo-controlled, phase 3 study in patients with nr-axSpA (Additional file 1: Fig. S1). Adult patients (aged ≥ 18) with a clinical diagnosis of nr-axSpA who met the ASAS classification criteria for axSpA and had objective signs of inflammation (MRI with (...truncated)