Session Information
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Statins are among the most frequently prescribed medications for
the treatment of dyslipidemia. Amongst users, between 9-20% of
patients will develop a self- limited myopathy in which
musculoskeletal symptoms may range from myalgia to rhabdomyolysis
(0.4/10 000 patient years)(1-4). In the last decade, there has been
considerable interest focusing on an association between statin
exposure, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase
(HMGCR) antibodies and autoimmune necrotizing myopathy. Systemic
sclerosis is a highly heterogenous disease characterized, among other
things, by autoantibodies and inflammatory myositis. The objective of
this study was to investigate the frequency of anti- HMGCR antibodies
in SSc and associations with inflammatory myositis and statin
exposure.
Methods:
This was a cross-sectional, multicenter study of 306 subjects from
the Canadian Scleroderma Research Group cohort who had complete data
on statin exposure and history of inflammatory myositis (recorded by
a study physician at baseline) and anti-HMGCR antibodies assayed by
an addressable laser bead immunoassay (ALBIA, Luminex, Austin, TX
(cutoff 200 units, high positive cutoff 500 units). Descriptive
statistics were used to summarize the baseline characteristics of the
subjects. Fisher’s exact test for categorical variables and Mann
Whitney U test for continuous variables were used to compute p
values. All statistical analyses were performed with SAS v.9.2 (SAS
Institute, USA).
Results:
Fifty-one (17%) subjects had anti-HMGCR antibodies, of which only
4 (1.3%) had high positive titers (Table 1). Subjects with high
positive anti-HMGCR antibodies titers tended to be older (mean
60.3+14.9 versus 56.1+12.5 years) compared to negative subjects. They
tended to have shorter disease duration (8.6+5.6 versus 11.2+9.0
years) and more diffuse skin involvement (75% versus 58%), pulmonary
hypertension (67% versus 10%, p=0.03) and interstitial lung disease
(75% versus 35%) compared to negative subjects. They also tended to
have more severe heart disease when measured on the Medsger Disease
Severity Scale (2.0+1.6 vs 0.5+0.9, p=0.005).
Of particular interest, though, none of the subjects with high
positive anti-HMGCR antibodies titers had a history of inflammatory
myositis, compared to 9% of those with negative titers. In addition,
none of those with high positive titers had past or current exposure
to statins compared to 11% of those with negative titers.
Conclusion:
High titer anti-HMGCR antibodies are rare in SSc (1.3%) but are
not associated with inflammatory myositis or statin exposure. Larger
studies will be required to confirm these preliminary observations.
Nevertheless, we conclude that anti-HMGCR antibodies are unlikely to
play a major role in inflammatory myositis in SSc and that high
titers can be present in subjects without exposure to statins.
Table 1
Baseline characteristics
|
|
(–)ve (N=255) |
Low (+)ve (N=47) |
High (+)ve (N=4) |
–ve vs High +ve p values |
||||||
|
|
Mean or N |
SD or % |
Mean or N |
SD or % |
Mean or N |
SD or % |
|
|||
|
Mean age, years |
56.1 |
12.5 |
56.4 |
10.8 |
60.3 |
14.9 |
0.650 |
|||
|
Female, % |
222 |
87.1% |
42 |
89.4% |
4 |
100% |
0.578 |
|||
|
White, % |
218 |
90.5% |
41 |
91.1% |
4 |
100% |
0.672 |
|||
|
Disease duration, years |
11.2 |
9.0 |
9.6 |
6.9 |
8.6 |
5.6 |
0.734 |
|||
|
Skin subsets, % |
|
|
|
|
|
|
0.354 |
|||
|
Limited |
154 |
60.6% |
35 |
74.5% |
3 |
75.0% |
|
|||
|
Diffuse |
100 |
39.4% |
12 |
25.5% |
1 |
25.0% |
|
|||
|
Modified Rodnan skin score |
9.7 |
9.6 |
9.5 |
8.9 |
13.7 |
4.7 |
0.135 |
|||
|
Number of GI symptoms (range 0-14) |
4.1 |
3.1 |
4.3 |
3.1 |
5.5 |
3.8 |
0.407 |
|||
|
Pulmonary hypertension, % |
22 |
10.0% |
5 |
12.5% |
2 |
66.7% |
0.030 |
|||
|
Interstitial lung disease, % |
88 |
35.2% |
15 |
32.6% |
3 |
75.0% |
0.117 |
|||
|
FVC, %predicted |
89.4 |
18.6 |
87.5 |
19.6 |
73.3 |
17.6 |
0.151 |
|||
|
DLCO, %predicted |
70.0 |
21.0 |
72.2 |
18.2 |
72.5 |
25.6 |
0.787 |
|||
|
Inflammatory myositis, % |
23 |
9.0% |
3 |
6.4% |
0 |
0% |
0.688 |
|||
|
CK (baseline) |
113.8 |
124.0 |
92.2 |
70.3 |
36.8 |
11.1 |
0.004 |
|||
|
Overlap with PM/DM, % |
6 |
2.4% |
0 |
0.0% |
0 |
0% |
0.910 |
|||
|
Medsger Disease severity scores (range 0-10) |
|
|
|
|
|
|
|
|||
|
General |
0.8 |
1.2 |
0.8 |
1.1 |
1.3 |
1.9 |
0.703 |
|||
|
Skin |
1.2 |
0.7 |
1.2 |
0.6 |
1.3 |
0.6 |
0.610 |
|||
|
Kidney |
0.1 |
0.6 |
0.0 |
0.0 |
0.0 |
0.0 |
0.594 |
|||
|
Peripheral vascular |
1.5 |
1.3 |
1.6 |
1.2 |
2.3 |
1.7 |
0.297 |
|||
|
Joint/tendon |
0.7 |
1.2 |
0.9 |
1.4 |
1.0 |
1.7 |
0.893 |
|||
|
Muscle |
0.2 |
0.7 |
0.3 |
0.9 |
0.5 |
1.0 |
0.370 |
|||
|
Gastrointestinal |
1.9 |
0.7 |
1.8 |
0.8 |
2.3 |
0.5 |
0.281 |
|||
|
Lung |
1.3 |
1.1 |
1.4 |
1.1 |
2.0 |
1.8 |
0.404 |
|||
|
Heart |
0.4 |
0.9 |
0.5 |
0.9 |
2.0 |
1.6 |
0.005 |
|||
|
Antibodies, % |
|
|
|
|
|
|
|
|||
|
Centromere |
92 |
36.1% |
19 |
40.4% |
3 |
75.0% |
0.124 |
|||
|
Topoisomerase |
36 |
14.1% |
11 |
23.4% |
0 |
0% |
0.548 |
|||
|
RNA Pol-III |
48 |
18.9% |
7 |
14.9% |
0 |
0% |
0.437 |
|||
|
Pm/Scl (PM1-alpha) |
17 |
6.8% |
4 |
18.5% |
0 |
0% |
0.758 |
|||
|
Statins |
|
|
|
|
|
|
0.631 |
|||
|
Current |
26 |
10.2% |
7 |
14.9% |
0 |
0% |
|
|||
|
In the past |
2 |
0.8% |
1 |
2.1% |
0 |
0% |
|
|||
|
Never |
227 |
89.0% |
39 |
83.0% |
4 |
100% |
|
|||
To cite this abstract in AMA style:
Luck Y. Anti 3-Hydroxy-3-Methylglutaryl-Coenzyme a Reductase in Systremic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/anti-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-in-systremic-sclerosis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-3-hydroxy-3-methylglutaryl-coenzyme-a-reductase-in-systremic-sclerosis/