A randomized, double-blind, placebo-controlled 12-week trial of infliximab in patients with juvenile-onset spondyloarthritis

Abstract

Objective To assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA). Methods Phase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ). Results We randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p = 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p < 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious. Conclusion Infliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed.

Comparison of biologics and small-molecule drugs in axial spondyloarthritis: a systematic review and network meta-analysis

“…All articles involved biologics, including TNFRFc [10 studies involving etanercept ( Davis et al, 2003 ; Calin et al, 2004 ; van der Heijde et al, 2006a ; Braun et al, 2011 ; Dougados et al, 2011 ; Song et al, 2011 ; Dougados et al, 2014a ; Dougados et al, 2014b ; Damjanov et al, 2016 ; Wei et al, 2018 )], TNFmAb [six studies involving adalimumab ( van der Heijde et al, 2006b ; Haibel et al, 2008 ; Horneff et al, 2012 ; Sieper et al, 2013 ; Huang et al, 2014 ; Landewé et al, 2018 ), three studies involving certolizumab ( Landewé et al, 2014 ; Deodhar et al, 2019a ; Landewé et al, 2020 ), five studies involving golimumab ( Inman et al, 2008 ; Bao et al, 2014 ; Tam et al, 2014 ; Sieper et al, 2015 ; Deodhar et al, 2018 ), and six studies involving infliximab ( Marzo-Ortega et al, 2005 ; van der Heijde et al, 2005 ; Giardina et al, 2010 ; Inman and Maksymowych, 2010 ; Sieper et al, 2014a ; Burgos-Vargas et al, 2022 )], IL17Ai [three studies involving ixekizumab ( van der Heijde et al, 2018b ; Deodhar et al, 2019c ; Deodhar et al, 2020c ), one study involving netakimab ( Erdes et al, 2020 ), and seven studies involving secukinumab ( Baeten et al, 2013 ; Baeten et al, 2015 ; Pavelka et al, 2017 ; Kivitz et al, 2018 ; Huang et al, 2020 ; Deodhar et al, 2021a )], IL17A/Fi [one study involving bimekizumab ( van der Heijde et al, 2020 )], IL17RAi [one study involving brodalumab ( Wei et al, 2021b )], IL6i [one study involving tocilizumab ( Sieper et al, 2014b )], IL12/23i [one study involving risankizumab ( Baeten et al, 2018 ) and three studies involving ustekinumab ( Deodhar et al, 2019b )], and PDE4i [two studies involving apremilast ( Pathan et al, 2013 ; Taylor et al, 2021 ...…”

“…All articles involved biologics, including TNFRFc [10 studies involving etanercept (Davis et al, 2003;Calin et al, 2004;van der Heijde et al, 2006a;Braun et al, 2011;Dougados et al, 2011;Song et al, 2011;Dougados et al, 2014a;Dougados et al, 2014b;Damjanov et al, 2016;Wei et al, 2018)], TNFmAb [six studies involving adalimumab (van der Heijde et al, 2006b;Haibel et al, 2008;Horneff et al, 2012;Sieper et al, 2013;Huang et al, 2014;Landewé et al, 2018), three studies involving certolizumab (Landewé et al, 2014;Deodhar et al, 2019a;Landewé et al, 2020), five studies involving golimumab (Inman et al, 2008;Bao et al, 2014;Tam et al, 2014;Sieper et al, 2015;Deodhar et al, 2018), and six studies involving infliximab (Marzo-Ortega et al, 2005;van der Heijde et al, 2005;Giardina et al, 2010;Inman and Maksymowych, 2010;Sieper et al, 2014a;Burgos-Vargas et al, 2022)], IL17Ai [three studies involving ixekizumab (van der Heijde et al, 2018b;Deodhar et al, 2019c;Deodhar et al, 2020c), one study involving netakimab (Erdes et al, 2020), and seven studies involving secukinumab (Baeten et al, 2013;Baeten et al, 2015;Pavelka et al, 2017;…”

Drug therapy in juvenile spondyloarthritis

“…The study met its primary endpoint with fewer flares in the etanercept group compared with placebo over 48 weeks [9]. A phase III, randomized, double-blinded placebo-control study of the efficacy and safety of infliximab in patients with JSpA less than 18 years of age who had failed NSAIDs and DMARDs met its primary endpoint with patients in the infliximab group showing significant reduction in AJC when compared with placebo [10]. Notably, adalimumab is FDA-approved for JIA in general but not specifically for JSpA whereas infliximab has no FDA indication for JIA and is used off label in clinical practice.…”

Advances in the Diagnosis and Treatment of Enthesitis-Related Arthritis

“…A trial of csDMARDs can be considered for subjects with enthesitis having contraindications to TNFi or concomitant active peripheral polyarthritis [88]. The effectiveness of TNFi in the treatment of ERA has been proven not only by retrospective analysis [55,97] but also by multiple randomized controlled trials [98][99][100][101][102][103]. Among TNFi, Etanercept is the most widely used in daily practice, while adalimumab is preferred in patients with concomitant uveitis.…”