Background/Purpose: In PMR careful tailoring of the glucocorticoid dosage to the patients needs is crucial to avoid the risk of treatment-related adverse effects and the disability associated with uncontrolled inflammation. The ESR and CRP are standard assays used to guide assessment of disease activity. Studies have demonstrated a discordance between ESR and CRP of 28% making assessment of disease activity a diagnostic challenge. Any biomarker that accurately reflects disease activity in PMR, thereby facilitating appropriate adjustment of glucocorticoid dose would be welcomed. Previously we have demonstrated that plasma fibrinogen is more specific for the confirmation of response to treatment than either ESR or CRP. Here we prospectively compare the ability of the biomarkers ESR, CRP and fibrinogen to distinguish between disease remission and disease activity in PMR.
Methods: 25 patients with newly diagnosed PMR and 35 patients with a known diagnosis were assessed at baseline and 6 weeks. Patients were divided into disease remission(Group 1) or persistent disease activity(Group 2),based on the Polymyalgia Rheumatica Activity Score (PMR-AS). A PMR-AS < 1.5 indicates disease remission with a PMR-AS >1.5 reflecting persistent disease activity. Plasma fibrinogen, CRP and ESR were assayed. An ESR value of 20mm/hr and CRP of 6mg/L(lab normal <5mg/l) were considered the upper limit for detection for remission. The upper limit of the lab normal for Fibrinogen(4g/L) was used. Sensitivity, specificity, positive predictive values and likelihood ratios was calculated for all biomarkers.
Results:
Data was available from 120 patient visits. Mean age was 71.8 years.Demographic data was similar between groups. A significant difference was observed in steroid dose between groups(10mg v 3.5mg p<.001).
All biomarkers were significantly higher in those with persistent disease activity(Group 2) compared to those in remission(Group 1)(p<.0001).
Overall 24 patients were defined as being in remission as per the PMR-AS. Of these 23/24 had a normal plasma fibrinogen with 18/24 having a normal ESR and 16/24 a CRP < 6mg/L. The specificity, sensitivity, positive predictive values and likelihood ratios for the different biomarkers are shown in the table below.
Specificity |
Sensitivity |
PPV |
Likelihood Ratio |
Fischers Exact Test |
|
Fibrinogen |
96% |
34% |
.97 |
8.2 |
P=.002 |
CRP |
67% |
68% |
.88 |
2.04 |
P=.004 |
ESR |
75% |
43% |
.87 |
1.7 |
P=.16 |
Plasma fibrinogen was more specific than ESR and CRP for differentiating between disease remission and disease activity. It also demonstrated a superior positive predictive value and likelihood ratio than ESR and CRP for identifying patients with persistent disease. The ESR showed no significant ability to distinguish between disease remission and activity (p=.16).
Conclusion:
Elevated plasma fibrinogen more accurately indicates that patients have persistent disease activity than either the ESR or CRP. Measurement of fibrinogen may therefore help treating physicians more accurately identify patients’ disease status and guide decisions with regards to glucocorticoid dosage.
Disclosure:
E. McCarthy,
None;
P. A. MacMullan,
None;
S. Al-Mudhaffer,
None;
A. M. Madigan,
None;
S. Donnelly,
None;
C. J. McCarthy,
None;
D. Kenny,
None;
E. Molloy,
None;
G. M. McCarthy,
None.
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