P124 Rheumatoid Arthritis with Normal CRP: an Underappreciated, Persistent Phenotype: Equally at Risk of Severe Disease
Authors: Hutchinson Matthew , Sethi Bhavika , Sritharan Gertheka , Greenaway Borgel , Jury Elizabeth , Manson Jessica 
Published: April 2023

Abstract

Background/Aims
A subset of seropositive rheumatoid arthritis (RA) with normal CRP levels during ultrasound-proven flairs was previously identified. They experienced worse outcomes, with delays in initiation of conventional DMARDs, more joint damage and higher disease activity scores, with an increased likelihood of needing biologic therapy. The aims were to longitudinally assess this group over 5 years - to determine the persistence of the phenotype and establish if differences in outcome were sustained; and to estimate the prevalence of this phenotype among the wider seropositive RA cohort at UCLH.

Methods
The initial study described two groups: those with high CRP during flare (hCRP) and those with normal CRP during flare (nCRP). The electronic health records of the initial cohort were interrogated. CRP measurements at 1-, 2- and 5-years post recruitment were collated. Clinical notes were examined to determine if episodes of raised CRP were due to RA activity, or alternative causes. Because of its CRP lowering properties, patients on Tocilizumab were excluded from this analysis. To screen for the nCRP phenotype in the larger population, DAS-28-CRP results were analysed from the 312 most recently reviewed patients in the UCLH seropositive RA database (data extracted 8th October 2019). The clinic letter from the time of the CRP value was examined, and patients were defined as having active disease if DAS-28 &gt; 4.5.

Results
Patients classified as nCRP at initial recruitment continued to have lower CRP (nCRP group median 1.1, maximum 6.4, hCRP group median 4, maximum 55.2, P = 0.0117). 1 patient originally classified as nCRP had a result &gt;5 at 5 years (6.4). Among the original cohort, at 5 years, patients originally defined as nCRP were more likely to require a biologic (76.67%) than hCRP (44.4%) (P = 0.0324). There was no significant difference in DAS-28 scores between groups at 5 years (hCRP median 3.2, nCRP median 2.9 P = 0.8775) . Patients with nCRP phenotype were as likely to have erosive disease as those in the hCRP cohort (hCRP 66.67%, nCRP 56.52%, P = 0.7356). Among the larger sample of 312 patients, 28 had CRP levels &lt; 5 and DAS-28 &gt;4.5. Of these, on longitudinal analysis of CRP at the time of clinic visits, 16/28 never mounted a CRP in response to active arthritis - likely the most representative of the nCRP patients from the original ultrasound cohort. These data suggest the nCRP phenotype represents at least 5% of the seropositive rheumatoid arthritis cohort at UCLH.

Conclusion
The subgroup of patients exhibiting normal CRP levels during disease flair maintain this phenotype over time. They remain more likely to require biologic treatment, while having equivalent DAS-28 scores and risk of damage to hCRP patients. Their presence as a significant minority of the wider population has implications for clinical care and resource use.
Disclosure
M. Hutchinson: None. B. Sethi: None. G. Sritharan: None. B. Greenaway: None. E. Jury: None. J. Manson: None.