Background/Purpose: Serial measurement of absolute eosinophil count (Eos), serum immunoglobulin E (IgE), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) is common practice in the care of patients with EGPA, yet the value of these tests as longitudinal biomarkers is largely anecdotal.
Methods: Subjects were enrolled in an observational EGPA cohort. Eos, IgE, ESR, and CRP were measured quarterly. BVAS/WG defined disease activity. Correlation among laboratory tests was derived using Spearman’s rank order test. The association of tests with disease activity was assessed via GEE logistic regression, adjusting for repeated measures and medication use (prednisone, other immunosuppressants). Survival analysis was used to determine if laboratory tests were predictive of 3-month future flare risk. Analyses were stratified by ANCA status.
Results: Among 141 subjects, there were clinico-demographic differences according to ANCA status (Table). Out of 892 observations, the majority (74%) occurred while subjects were taking prednisone or other immunosuppressants. Correlations among Eos, IgE, ESR, and CRP were mostly low or non-significant (range r = -0.08 to 0.43) and differed by ANCA status and medication use. There were few significant, but clinically weak, associations with disease activity (Eos: OR=1.01 per 100 units, 95% CI 1.01-1.02 in both ANCA negative and positive subjects; CRP: OR=1.62 per 10 mg/L increase, 95%CI 1.57-1.67 in ANCA-negative subjects). When BVAS/WG ³1 defined active disease, only Eos (HR=1.02 per 100 units, 95%CI 1.01-1.03) was predictive of flare. When BVAS/WG ³3 defined active disease, only ESR was predictive of flare (HR=1.52 per 10 mm/hr increase, 95% CI 1.27-1.71).
Conclusion: Eos, IgE, ESR, and CRP have limited value as longitudinal biomarkers of disease activity or predictors of flare in EGPA. Only Eos was consistently associated with disease activity but the association was quite weak. The relationship of these labs to each other and their value as biomarkers differed according to ANCA status. These findings question the routine use of these tests to guide therapy in EGPA and suggest that novel biomarkers of disease activity for EGPA are needed.
Table: Clinical and Demographic Differences in EGPA cohort by ANCA status
|
Variable
|
Total
|
ANCA Negative
|
ANCA Positive
|
|
No. subjects
|
141 |
76 (54%) |
65 (46%) |
|
No. observations
|
892 |
490 |
402 |
|
Sex, female* |
82 (58%) |
53 (70%) |
29 (45%) |
|
Age at first observation, years (median, range) |
55 (21-82) |
51 (21-82) |
57 (23-82) |
|
Race, white |
131 (93%) |
72 (95%) |
59 (91%) |
|
Disease duration at first observation, years (median, range)
|
1.5 (0-29.8) |
1.6 (0-21.7) |
1.3 (0-29.8) |
|
On prednisone* # observations
|
579 (65%) |
348 (71%) |
231 (57%) |
|
On other medications,# # observations
|
423 (47%) |
245 (50%) |
178 (44%) |
|
On either prednisone or other medications, # observations
|
659 (74%) |
376 (77%) |
283 (70%) |
|
BVAS_WG |
0: 766 (86%) ³1: 99 (11%) ³3: 33 (4%)
|
0: 414 (85%) ³1: 56 (11%) ³3: 17 (3%) |
0: 352 (88%) ³1: 43 (11%) ³3: 16 (4%) |
|
Eosinophil count, 10 3/mm (median, range)
|
262.0 (0-18,096) |
276.0 (0-7,083) |
229.4 (0-18,096) |
|
Immunoglobulin E , mg/dL* (median, range)
|
60.0 (0-21,925) |
38.4 (0-21,925) |
85.0 (2-7,298) |
|
ESR, mm/hr (median, range)
|
8.0 (1-94) |
8.0 (1-72) |
8.0 (1-94) |
|
CRP, mg/L (median, range)
|
2.2 (0-203) |
2.0 (0-98) |
2.6 (0-203) |
* Indicates statistically significant differences (p<0.01) between ANCA positive and ANCA negative subjects with EGPA. Categorical variables were assessed by Fisher's exact test and continuous variables were assessed by Wilcoxon rank sum test.
# Other medications= azathioprine, cyclophosphamide, methotrexate, or mycophenolate mofetil.
Disclosure:
P. C. Grayson,
None;
P. A. Monach,
Genentech and Biogen IDEC Inc.,
2;
D. Cuthbertson,
None;
S. Carette,
None;
G. S. Hoffman,
None;
N. A. Khalidi,
None;
C. L. Koening,
None;
C. A. Langford,
None;
K. Maksimowicz-McKinnon,
None;
C. Pagnoux,
None;
P. Seo,
None;
U. Specks,
None;
S. R. Ytterberg,
None;
P. A. Merkel,
None.
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