Certolizumab Pegol Efficacy in Patients With Non-Radiographic Axial Spondyloarthritis Stratified by Baseline MRI and C-Reactive Protein Status: An Analysis From the C-axSpAnd Study

Abstract

Objective: Tumor necrosis factor inhibitors (TNFi) are an effective treatment for non-radiographic axial spondyloarthritis (nr-axSpA). To be eligible, however, many authorities require patients with nr-axSpA to show active sacroiliitis on magnetic resonance imaging (MRI) and/or an elevated C-reactive protein (CRP) level, possibly resulting in a perception that patients with nr-axSpA without both factors have only low responses to TNFi treatment. We evaluated clinical responses to certolizumab pegol (CZP) in patients with nr-axSpA stratified by baseline MRI/CRP status.

Methods: C-axSpAnd was a phase 3, multicenter study on CZP in adult patients with active nr-axSpA and objective signs of inflammation. This analysis assessed efficacy of CZP over the 52-week randomized, double-blind, placebo-controlled period in patients stratified into subgroups based on the presence of active sacroiliitis on MRI and CRP level at baseline.

Results: CZP-treated patients across all MRI/CRP subgroups achieved clinical responses greater than placebo. Across outcome measures, CZP-treated MRI+/CRP+ patients demonstrated the greatest clinical responses, but substantial improvements were also observed in CZP-treated MRI+/CRP- and MRI-/CRP+ patients. Ankylosing Spondylitis Disease Activity Score Major Improvement response rates at week 52 among CZP-treated patients (75.6% MRI+/CRP+; 47.5% MRI-/CRP+; and 29.7% MRI+/CRP-) were higher than rates in placebo groups (range: 3.9%-12.5%). Assessment of SpondyloArthritis international Society 40% response, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondyloarthritis Functional Index had similar response patterns, although differences between the CZP-treated MRI/CRP subgroups were smaller. Clinical responses among CZP-treated patients were also observed in additional subgroups, including those with low Spondyloarthritis Research Consortium of Canada MRI sacroiliac joint inflammation scores and those with normal baseline CRP levels.

Conclusion: Our findings indicate that CZP treatment benefits patients with nr-axSpA across MRI+/CRP+, MRI-/CRP+, and MRI+/CRP- subgroups.

© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Figures

Figure 1

Clinical efficacy outcomes in patients stratified by baseline MRI/CRP status. Randomized set (N = 317). Missing values, or values collected after switching to open‐label CZP, were imputed using NRI for dichotomous variables and LOCF for continuous variables: at week 52, data were available for 121/159 patients randomized to CZP and 51/158 patients randomized to PBO. ASDAS‐MI, Ankylosing Spondylitis Disease Activity Score; CfB, change from baseline; CRP, C‐reactive protein; CZP, certolizumab pegol; LOCF, last observation carried forward; MRI, magnetic resonance imaging; NRI, non‐responser imputation; PBO, placebo.

Figure 2

ASDAS states in patients stratified by baseline MRI/CRP status. Randomized set (N = 317); LOCF. ASDAS‐HD: ASDAS ≥2.1 and ≤3.5; ASDAS‐ID: ASDAS 3.5. ASDAS, Ankylosing Spondylitis Disease Activity Score; ASDAS‐HD, Ankylosing Spondylitis Disease Activity Score high disease activity; ASDAS‐ID, ASDAS‐inactive disease; ASDAS‐LDA, ASDAS‐low disease activity; ASDAS‐vHD, Ankylosing Spondylitis Disease Activity Score very high disease; CRP, C‐reactive protein; CZP, certolizumab pegol; LOCF, last observation carried forward; MRI, magnetic resonance imaging; PBO, placebo.

Figure 3

Clinical efficacy outcomes in patients stratified by baseline SPARCC MRI SI Joint Inflammation score. Analysis set comprised 310 patients from the randomized patient population who had SPARCC SI joint scores recorded from MRI scans at screening. Missing values, or values collected after switching to open‐label CZP, were imputed using NRI for dichotomous variables and LOCF for continuous variables: at week 52, data from this analysis set were available for 110/156 patients randomized to CZP and 46/154 patients randomized to PBO. ASAS40, Assessment of SpondyloArthritis international Society 40% response; ASDAS‐MI, Ankylosing Spondylitis Disease Activity Score‐Major Improvement; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CfB, change from baseline; CZP, certolizumab pegol; LOCF, last observation carried forward; NRI, non‐responser imputation; PBO, placebo; SPARCC, Spondyloarthritis Research Consortium of Canada.

Figure 4

Clinical efficacy outcomes in patients stratified by baseline CRP. Randomized set (N = 317). Missing values, or values collected after switching to open‐label CZP, were imputed using NRI for dichotomous variables and LOCF for continuous variables: at week 52, data were available for 121/159 patients randomized to CZP and 51/158 patients randomized to PBO. ASAS40, Assessment of SpondyloArthritis international Society 40% response; ASDAS‐MI, Ankylosing Spondylitis Disease Activity Score‐Major Improvement; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; CfB, change from baseline; CRP, C‐reactive protein; CZP, certolizumab pegol; LOCF, last observation carried forward; NRI, non‐responser imputation; PBO, placebo.