Background/Purpose: Certolizumab pegol (CZP), an Fc-free, PEGylated tumor necrosis factor (TNF) inhibitor, has previously demonstrated efficacy and safety in patients with radiographic (r) and non-radiographic (nr) axial spondyloarthritis (axSpA).^1,2 In nr-axSpA patients, CZP has demonstrated efficacy across all C‑reactive protein (CRP) subgroups, including patients with normal baseline CRP levels.³ However, the association between CZP efficacy and baseline CRP levels has not been investigated in the subset of nr-axSpA patients with positive magnetic resonance imaging (MRI+; defined as the presence of active sacroiliitis on MRI based on the Assessment of SpondyloArthritis international Society [ASAS] criteria).⁴ This post-hoc analysis explores the association between baseline CRP levels and CZP efficacy in MRI+ nr-axSpA patients from the C‑OPTIMISE trial.

Methods: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with r-axSpA or nr-axSpA.^1,2 In the open-label run-in period (0–48 weeks), patients received CZP 400 mg at Weeks 0, 2, and 4, then CZP 200 mg every 2 weeks thereafter. This analysis included the subset of MRI+ nr‑axSpA patients in the C‑OPTIMISE cohort who received ≥1 dose of study medication in the open-label period. Efficacy outcomes were evaluated and stratified by baseline CRP levels ( <5 mg/L, ≥5– < 10 mg/L and ≥10 mg/L). The upper limit of normal of the CRP assay was defined as 9.99 mg/L by the central laboratory. The lower limit of quantification (LLoQ) was 4 mg/L; where CRP levels < LLoQ, a CRP value of 2 mg/L was used to calculate Ankylosing Spondylitis Disease Activity Score (ASDAS).⁵ Outcomes included ASAS ≥40% improvement (ASAS40), ASDAS – major improvement (ASDAS-MI), ASAS partial remission (ASAS PR), ASDAS, BASDAI, and BASFI.

Results: In total, 275 MRI+ nr-axSpA patients were included in this analysis (CRP <5 mg/L: n=156; CRP ≥5– <10 mg/L: n=38; CRP ≥10 mg/L: n=81). Response rates for ASAS40 increased over the treatment period and were comparable across CRP subgroups (Figure 1A). Response rates for ASDAS-MI were higher in the CRP ≥10 mg/L and CRP ≥5– <10 mg/L subgroups than the CRP <5 mg/L subgroup (Figure 1B). Across other efficacy measures, improvements were observed at Week 48 compared with baseline in all CZP-treated CRP subgroups (Table 1).

Conclusion: Clinically relevant responses were observed in MRI+ nr-axSpA patients treated with CZP, across CRP subgroups and measured outcomes. The responses in each subgroup were consistent with those previously reported in total nr-axSpA patient group.¹ ASDAS-MI response rates were lower in the CRP <5 mg/L subgroup, however, CRP is a key factor in ASDAS derivation. It is unlikely that ASDAS-MI could be achieved in patients in the CRP <5 mg/L subgroup since most of them had CRP levels < LLoQ.

References: 1. Landewé R et al. Rheumatol Ther 2020;7:581–99. 2. Landewé R et al. Ann Rheum Dis 2020;79:920–28. 3. Robinson P et al. Int J Rheum Dis 2020;23:67–8. 4. Rudwaleit M et al. Ann Rheum Dis 2009;68:1520–7. 5. Machado P et al. Arthritis Rheumatol 2015;67:408–13.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/response-to-certolizumab-pegol-in-patients-with-non-radiographic-axial-spondyloarthritis-by-baseline-c-reactive-protein-cut-offs-post-hoc-analysis-from-a-phase-3-multicenter-study/