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COHORT STUDY
Personal non-commercial use only. The Journal of Rheumatology Copyright 2016. All rights reserved.
All data for this study were collected from patients enrolled between 2006
and 2013 in the Vasculitis Clinical Research Consortium Longitudinal Study
of Giant Cell Arteritis, a multicenter, prospective, observational cohort. All
patients in this cohort meet the 1990 American College of Rheumatology
classification criteria for GCA25, which was modified to include patients
with large-vessel vasculitis by angiography or biopsy. Inclusion criteria were
age above 50 years with 2 of the following features: (1) new localized
headache, (2) temporal artery abnormality on examination, (3) erythrocyte
sedimentation rate (ESR) > 40 mm/h by Westergren method, (4) abnormal
temporal artery biopsy, and (5) large vessel vasculitis by angiography or
biopsy. All subjects were followed prospectively with standardized clinical
assessments including symptoms attributable to vasculitis (over the past 28
days, on the day of evaluation), laboratory findings, BVAS (version 2, which
includes 66 items grouped into 9 organ systems), and physicians global
assessment (PGA, scale of 0-10). Disease activity was also assessed categorically by the treating physician at each visit as remission or active (low,
moderate, or high). Disease activity was defined as the presence of new or
worsening symptoms attributable to active vasculitis in the 28 days prior to
evaluation or on the day of evaluation.
Information was reviewed on symptoms, laboratory evaluation, PGA,
and BVAS during any period of disease activity in the 28 days prior to the
visit, or on the date of the visit. The distribution of organ involvement as
documented in the BVAS was collected. The investigator completing the
BVAS separates symptoms that are new or worse from those that have been
present within the last 3 months and continue to be present (persistent). There
are 2 final BVAS scores: BVAS1 (new/worse) and BVAS2 (persistent).
Additional symptoms attributed to vasculitis that were not recorded by the
BVAS except in the Other category were also collected. Manifestations of
2
active vasculitis placed under the Other category of BVAS do not add to
the total BVAS and are scored as 0. Descriptive statistics were used.
Spearmans rank correlation was used to evaluate the correlation of the
BVAS in patients with active disease with other measures of disease activity
including PGA, physician-rated disease activity (remission, low, moderate
or high), ESR, and C-reactive protein (CRP). JMP, Version 11, SAS Institute
Inc., was used for all analyses.
The study was approved by institutional review boards at each participating site. All participants provided informed consent.
RESULTS
Data were available for 136 subjects: 100 (74%) female,
mean (SD) age at study entry of 71.7 (9.3) years with a mean
(SD) followup of 2.3 (1.6) years. Symptoms of active GCA
were present in 236 visits. Median (range) BVAS1 (new or
worse symptoms) was 1 (0-10) and median (range) BVAS2
(persistent symptoms) was 0 (0-5) in the 236 visits with
active disease. Median (range) PGA was 4 (0-9) for disease
activity in the past 28 days and 2 (0-9) for activity on the day
of the visit. Disease activity for the past 28 days was characterized as remission for 7 visits, low for 75 visits, moderate
for 72 visits, and high for 32 visits. Disease activity on the
day of evaluation was categorized as remission in 48 visits,
low in 124 visits, moderate in 51 visits, and high in 10 visits
(data missing in 3 cases). On the day of evaluation, median
(range) ESR was 21 (1-126) mm/h, with median (range) CRP
of 6.65 (0-211.7) mg/l.
In 51 patients (38% of patients in this study) with active
disease at the time of enrollment, the diagnosis of GCA was
made within 3 months of enrollment into the cohort. In these
patients, median (range) BVAS1 at first visit was 3 (0-9), and
with BVAS2, 0 (0-5). Disease activity for the past 28 days
was rated as low in 1 patient, moderate in 24 patients, and
high in 24 patients (data missing in 2 patients). Disease
activity on day of evaluation (study enrollment) was categorized as remission in 15 patients, low in 16 patients,
moderate in 13 patients, and high in 6 patients. Median
(range) PGA for past 28 days was 7 (2-9) and 2 (0-9) for the
day of the visit (at study enrollment).
Symptoms of active vasculitis during the 236 visits with
active disease and whether they were identified on BVAS are
summarized in Table 1. Clinical manifestations of active
disease as collected by BVAS for the 236 visits are in Table
2. The BVAS was also separately analyzed for 51 patients
with GCA diagnosed within 3 months of enrollment into the
cohort (Table 3).
The most-used categories of BVAS were the General
category, followed by Other, and Mucus Membranes/Eyes. Forty-eight (73%) of the 66 items in the 9
organ systems were never used. Further, 57 (86%) of the 66
items in the 9 organ systems were recorded in < 3% of visits
when active disease was present. The different categories of
the individual questions in the BVAS that were applicable to
any encounter with symptoms of active vasculitis are given
in Figure 1. All of the components in the General section of
the BVAS were applicable to patients with GCA while none
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Symptoms
Weight loss
Fever
Headache
Scalp tenderness
New temporal artery pain
Carotidynia
Jaw/tongue claudication
Ischemic retinopathy
Partial vision loss
Severe vision loss
Diplopia
Polymyalgia rheumatica
Arthralgia/arthritis
Upper extremity claudication
Lower extremity claudication
Transient ischemic attack
Light-headedness
Mesenteric ischemia
Other (fatigue, cough, night
sweats, anorexia)
17
7
98
66
43
16
64
14
14
5
9
79
28
35
12
1
5
1
21
13
11
53
30
17
7
29
5
7
3
1
53
40
29
9
0
5
1
15
8
3
33
27
20
9
26
10
5
5
8
16
11
9
4
0
0
1
4
DISCUSSION
In this large cohort of patients with GCA, the BVAS had
limited utility in the assessment of disease activity. Most
categories of the BVAS were not applicable in patients with
GCA. Additionally, because many components of active
vasculitis in GCA were placed in the Other category on the
BVAS and do not contribute to the total BVAS, some patients
had a BVAS of 0 despite active disease. This analysis raises
8
3
32
24
18
10
27
10
8
5
8
17
10
9
4
0
0
1
4
5
0
11
6
3
5
9
5
5
3
0
10
3
8
3
0
0
0
1
Yes
Yes
Yes
Yes (as headache)
Yes (as headache)
No
No
No
Yes
Yes
No
Yes
Yes
No
No
No
No
Yes
Yes for fatigue
and cough
concerns for use of the BVAS in clinical trials of new treatments for GCA.
There are numerous challenges in the clinical assessment
of disease activity and an objective measure would be
beneficial. Presently, there are no standardized measures of
disease activity in GCA. Previous clinical trials have used
terms such as relapses, recurrences, flares, or remission to
define disease activity and often take into consideration
markers of inflammation11,12,13,14,15,16,17,18,19. GCA is a
chronic granulomatous vasculitis, with observational cohorts
reporting at least 1 disease relapse in 28%-64% of
patients2,3,4,5,7,9,10. While markers of inflammation such as
ESR and CRP are neither sensitive nor specific in the
assessment of disease activity8,26,27, they are frequently used
to assess disease activity in patients with GCA and may
influence treatment decisions. Suspected relapses are often
treated with higher doses of glucocorticoids, which are
associated with significant morbidity in this population of
patients2,3. The BVAS is a validated tool for assessment of
disease activity for systemic vasculitis21,22,23. However,
previous validation studies evaluating the BVAS for
assessment of disease activity in systemic vasculitis have
included only a small number of patients with GCA21,23.
Additionally, in a validation study of BVAS version 3,
patients with GCA were excluded because of homogeneity
of clinical manifestations and a limited range of abnormalities
that would be measured by the BVAS items23. Few studies
have used BVAS in the assessment of disease activity in
Personal non-commercial use only. The Journal of Rheumatology Copyright 2016. All rights reserved.
Table 2. Frequency of clinical manifestations in 236 encounters of giant cell arteritis with active disease during
observation, as captured by the Birmingham Vasculitis Activity Score (BVAS).
BVAS Items (by organ system)
General, n = 188
Malaise
Myalgia
Arthralgia/arthritis
Headache
Fever (< 38.5C)
Fever (> 38.5C)
Weight loss ( 2 kg)
Maximum allowable score on BVAS
Median (range) BVAS for category
Cutaneous, n = 2
Ulcer
Maximum allowable score on BVAS
Median (range) BVAS for category
Mucous membranes/eyes, n = 35
Mouth ulcers
Blurred vision
Sudden vision loss
Maximum allowable score on BVAS
Median (range) total BVAS for category
Ear, nose, and throat, n = 1
Sinus involvement
Maximum allowable score on BVAS
Median (range) total BVAS for category
Chest, n = 9
Persistent cough
Maximum allowable score on BVAS
Median (range) total BVAS for category
Cardiovascular, n = 2
Congestive heart failure
Maximum allowable score on BVAS
Median (range) BVAS for category
Abdominal, n = 1
Severe abdominal pain
Maximum allowable score
Median (range BVAS for category)
Renal, n = 0
Maximum allowable score on BVAS
Median (range) BVAS for category
Nervous system, n = 4
Organic confusion/dementia
Stroke
Sensory peripheral neuropathy
Maximum allowable score on BVAS
Median (range) BVAS for category
Other, n = 85
Total
Maximum allowable score
Median (range) total BVAS
New/worse Symptoms*
Persistent Symptoms*
57
51
47
108
4
2
20
3
1 (03)
17
7
17
9
1
2
0
2
0 (02)
0
24
19
6
0 (06)
1
1
0
3
0 (02)
2
6
0 (04)
0
6
0 (00)
8
6
0 (02)
0
6
0 (00)
1
9
0 (03)
12
0 (00)
2
1
0
9
0 (09)
63
63
1 (010)
0
3
0 (00)
1
3
0 (01)
1
3
0 (01)
2
3
0 (02)
0
4
0 (00)
6
0 (00)
0
0
1
6
0 (03)
22
33
0 (05)
*Values are number of encounters during active disease with symptoms identified by that item. All median BVAS
are scores for 236 encounters with active disease. n = total number with any clinical manifestation in that organ
system.
Personal non-commercial use only. The Journal of Rheumatology Copyright 2016. All rights reserved.
Table 3. Frequency of active disease in 51 patients with newly diagnosed giant cell arteritis, as identified by the
Birmingham Vasculitis Activity Score (BVAS). All median BVAS are scores for 236 encounters with active disease.
BVAS Items (by organ system)*
General, n = 43
Malaise
Myalgia
Arthralgia/arthritis
Headache
Fever (< 38.5C)
Fever (> 38.5C)
Weight loss ( 2 kg)
Median (range) BVAS for category
Mucous membranes/eyes, n = 18
Blurred vision
Sudden vision loss
Retinal hemorrhage
Median (range) total BVAS for category
Chest, n = 5
Persistent cough
Median (range) total BVAS for category
Cardiovascular, n = 1
Congestive heart failure
Median (range) BVAS for category
Other, n = 19
Total median (range) BVAS
New/worse Symptoms
Persistent Symptoms
16
11
9
36
1
1
10
1 (03)
3
0
1
1
1
1
0
0 (02)
16
12
1
0 (06)
4
0 (02)
0
0 (00)
19
3 (09)
0
0
0 (00)
1
0 (01)
1
0 (02)
0
0 (05)
*No symptoms were found for these BVAS items: cutaneous; ear, nose, and throat; abdominal; renal; and nervous
system. n: total number with any clinical manifestation in that organ system.
Figure 1. Percentage of BVAS questionnaire components, arranged by category, that were applicable to any
patient with giant cell arteritis and active disease. ENT: ear, nose, and throat; BVAS: Birmingham Vasculitis
Activity Score.
Personal non-commercial use only. The Journal of Rheumatology Copyright 2016. All rights reserved.
Table 4. Spearmans correlations of BVAS with other measures used to assess disease activity in GCA.
PGA past 28 days
PGA today
ESR
CRP
Disease activity
past 28 days*
Disease activity today
BVAS1
0.50
0.01
0.02
0.02
0.46
0.05
BVAS2
< 0.001
0.40
0.18
0.04
< 0.001
0.62
0.80
0.77
0.20
0.08
0.12
0.01
PGA 28 Days
0.001
0.50
0.90
0.003
0.26
0.08
0.93
0.29
0.08
0.01
PGA Today
< 0.001
0.93
< 0.001
0.22
0.9
0.41
0.36
< 0.001
< 0.001
< 0.001
* Rated by evaluating physician as remission, low, medium, or high. BVAS: Birmingham Vasculitis Activity Score; BVAS1: score for new/worse disease
activity; BVAS2: score for persistent disease activity; GCA: giant cell arteritis; PGA: physicians global assessment; ESR: erythrocyte sedimentation rate; CRP:
C-reactive protein.
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