A single determination of C-reactive protein does not suffice to declare a patient with a diagnosis of axial spondyloarthritis \u2018CRP-negative\u2019

Robert Landewé,Owen Davies,Tommi Nurminen,Dominique Baeten

doi:10.1186/s13075-018-1707-8

Abstract

BackgroundTo be eligible to receive treatment with an anti-tumour necrosis factor (TNF), non-radiographic axial spondyloarthritis (nr-axSpA) patients require either elevated levels of C-reactive protein (CRP) (CRP > upper limit of normal (ULN)) or magnetic resonance imaging assessment showing inflammation of the sacroiliac joints, in addition to meeting criteria for high disease activity. Many axSpA patients are classified as ‘CRP-negative’, or CRP normal, despite having levels close to the ULN, and are therefore formally ineligible for treatment. The aim of this study was to investigate the likelihood of a CRP test indicating elevated levels in axSpA patients that have previously tested CRP normal.MethodsRAPID-axSpA (NCT01087762) enrolled patients who were either magnetic resonance imaging positive or had elevated CRP (> ULN: 7.9 mg/L). CRP data from the double-blind period for placebo-randomised patients until re-randomisation to certolizumab pegol (week 16 for ASAS20 non-responders/week 24 for ASAS20 responders) were analysed. CRP was assessed at screening, baseline, and nine time points to week 24. Linear mixed models were used to investigate time trends, variability, and correlations of CRP data.ResultsOf 106 placebo-randomised patients with baseline CRP assessments, 26 (25%) tested CRP normal at baseline, of whom 13 (50%) had ≥ 1 test indicating elevated CRP to week 16. Of 80/106 (75%) patients with elevated baseline CRP, 25 (31%) had ≥ 1 normal CRP test to week 16. Linear mixed models did not reveal changes in mean CRP across placebo patients from baseline to week 24.ConclusionsIn axSpA patients with CRP < ULN the CRP test should be repeated after ≥ 4 weeks as there is a substantial chance of finding a positive result for elevated CRP at subsequent testing, thereby allowing the patient access to treatment.Trial registrationClinicalTrials.gov, NCT01087762. Registered on 16 March 2010.

Highlights

To be eligible to receive treatment with an anti-tumour necrosis factor (TNF), non-radiographic axial spondyloarthritis patients require either elevated levels of C-reactive protein (CRP) (CRP > upper limit of normal (ULN)) or magnetic resonance imaging assessment showing inflammation of the sacroiliac joints, in addition to meeting criteria for high disease activity
The natural degree of CRP fluctuation in patients who have not received anti-TNF therapy is not well understood [17], and should be investigated further. In this post-hoc analysis of data from a phase 3 randomised controlled trial, we evaluated the consistency of CRP testing in patients with active Axial spondyloarthritis (axSpA)
Patient disposition and baseline characteristics In RAPID-axSpA, a total of 325 patients were randomised to treatment at week 0, 107 to placebo, and 218 to certolizumab pegol (CZP)

Summary

Introduction

To be eligible to receive treatment with an anti-tumour necrosis factor (TNF), non-radiographic axial spondyloarthritis (nr-axSpA) patients require either elevated levels of C-reactive protein (CRP) (CRP > upper limit of normal (ULN)) or magnetic resonance imaging assessment showing inflammation of the sacroiliac joints, in addition to meeting criteria for high disease activity. Many axSpA patients are classified as ‘CRP-negative’, or CRP normal, despite having levels close to the ULN, and are formally ineligible for treatment. Four anti-TNFs have been approved by European regulatory authorities for the treatment of patients with active nr-axSpA on the condition that they must exhibit objective signs of inflammation, demonstrated by magnetic resonance imaging (MRI) and/or elevated levels of C-reactive protein (CRP) [10,11,12]

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