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

Abstract

Background: 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 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.

Methods: RAPID-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.

Results: Of 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.

Conclusions: In 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 registration: ClinicalTrials.gov, NCT01087762 . Registered on 16 March 2010.

Keywords: C-reactive protein; Inflammation; Non-radiographic axial spondyloarthritis.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol, amendments, and subject informed consent were reviewed by a national, regional, or Independent Ethics Committee (IEC) or Institutional Review Board (IRB). This study was conducted in accordance with the current version of the applicable regulatory and International Conference on Harmonisation (ICH)-Good Clinical Practice (GCP) requirements, the ethical principles that have their origin in the principles of the Declaration of Helsinki, and the local laws of the countries involved. Informed consent was obtained from subjects and documented in accordance with local regulations, ICH-GCP requirements, and the ethical principles that have their origin in the principles of the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

RL has received consultancy fees and/or research grants and/or speaker’s bureau from AbbVie, Ablynx, Amgen, AstraZeneca, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Novartis, Merck, Pfizer, Roche, Schering-Plough, and UCB Pharma. TN is an employee of UCB Pharma. OD is an employee and stockholder of UCB Pharma. DB has acted as an advisor and/or provided research collaboration for AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB Pharma, and is an employee of UCB Pharma.

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Figures

Fig. 1

Percentage of C-reactive protein (CRP) tests subsequently elevated or normal by previous CRP level. Based on all available within-patient pairs of CRP assessment 4 or 12 weeks apart. Data included are from weeks 0, 4, 8, 12, 16, 20, and 24. Elevated CRP was defined as CRP > ULN (7.9 mg/L) and values ≤ 7.9 mg/L were considered normal