Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT

Jürgen Braun,Sibylle Haemmerle,Marleen Van De Sande,Hideto Kameda,Helena Marzo-Ortega,Hanno B Richards,Anna S Wiksten,Lianne S Gensler,Ricardo Blanco,Brian O Porter,Abhijit Shete,Filip Van Den Bosch,Denis Poddubnyy,Stephen Hall,Atul Deodhar

doi:10.1186/s13075-021-02613-9

Abstract

BackgroundTo investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex.MethodsThe phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex.ResultsEfficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P < 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively.ConclusionsSecukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients.Trial registrationClinicalTrials.gov, NCT02696031. Registered on 02 March 2016

Highlights

To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex
This report of efficacy outcomes from a subgroup analysis of the PREVENT study assessed the efficacy of secukinumab in patients with nr-Axial spondyloarthritis (axSpA) across important subgroups of CRP, MRI, and HLA-B27 status and in male and female patients
A similar trend was observed in the CRP subgroups for the treatment differences between secukinumab and placebo in ASAS40 responses, with higher response rates noted for the CRP+ (> 5 mg/L) subgroup compared with those for the CRP− (≤5 mg/L) subgroup

Summary

Introduction

To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. Axial spondyloarthritis (axSpA) is a chronic inflammatory disease, with an estimated prevalence of no less than 0.5% in the global population [1]. Nr-axSpA may progress to r-axSpA or AS over the course of the disease. Spinal inflammation can be visualized using magnetic resonance imaging (MRI) and new bone formation using conventional radiography [2,3,4,5,6,7,8]. Patients with nr-axSpA can show a comparable disease activity and burden as patients with r-axSpA or AS. The rate of progression from nr-axSpA to AS varies over the years, with a lifetime risk of progression of approximately 50% [8,9,10,11,12,13]

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