Session Information
Session Title: Muscle Biology, Myositis and Myopathies: Clinical and Therapuetic Aspects of Idiopathic Inflammatory Myopathies
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Statin use is associated with myalgias, muscle weakness and elevated muscle enzymes, but recent reports of a statin-induced immune-mediated necrotizing myopathy (IMNM) have been intriguing. Of particular interest is the recently reported hydroxy-3-methylglutaryl-coenzyme A reductase antibody (anti-HMGCoR). Our Aim is to evaluate anti-HMGCoR antibody positivity and statin exposure in antibody negative necrotizing myopathy patients.
Methods: Using a large prospective computerized database we identified 48 patients with antibody negative Necrotizing Myopathy from 1980-2011, confirmed by a pathologist- review of all biopsies. As a comparison cohort we had SRP positive myositis patients (32), a subset known to have necrotizing myopathy with poor prognosis. Other controls were Non-SRP non-necrotizing myositis patients (73), non-myositis controls (21), antibody positive necrotizing myopathy controls (13). A validated anti-HMGCoR ELISA assay was done on all cases and controls with values (units/ml) as negative < 20, low positive 20-39, medium positive 40-59, high positive at ≥ 60. Computerized database and clinical chart review was done for history of statin use and other clinical parameters. Chi square test was used to compare between cases and various controls for statin use and anti-HMGCoR positivity. All myositis specific autoantibody testing was done in a research lab using ELISA and immunoprecipitation.
Results: 256 biopsies were reviewed and 48 identified as antibody negative necrotizing myositis. Anti-HMGCoR positivity was significantly (p<0.001) associated with antibody negative necrotizing myopathy 47.9% (23/48) as compared to a) all myositis and non-myositis controls 7.2% (10/139), b) SRP control alone 0% (0/32), c) Non-SRP non-necrotizing myositis controls 5.5% (4/73), but not when compared alone to antibody positive necrotizing myopathy (4/13) (with 2 on statin), P =0.54).
Higher titer anti-HMGCoR levels were seen in antibody negative (17/48) and antibody positive necrotizing myopathy (4/13) but not in other controls (2/126). Statin use was more common (p<0.001) in antibody negative necrotizing myopathy (23/ 48) as compared to all myositis and non-myositis control (17/127), b) SRP control alone (2/26), c) Non-SRP non-necrotizing myositis control (11/70) but only trend compared alone to antibody positive necrotizing myopathy (3/13 (with 2 anti-HMGCoR +) P =0.06).
Within patients with necrotizing myopathy: anti-HMGCoR was associated with patients on statin (19/24) as compared to patients without statin (7/27), p <0.01). Anti-HMGCoR antibodies were more common in any patients on statin (20/34) as compared to patients without statin (20/138), p < 0.001).
Conclusion: Anti-HMGCoR is strongly associated with antibody (-) necrotizing myopathy vs. anti-SRP (+) myositis. Moreover, anti-HMGCoR is more common in necrotizing myopathy pts with history of statin use vs. no statin use.
Disclosure:
A. Malik,
None;
R. Aggarwal,
None;
Z. Qi,
None;
N. Fertig,
None;
D. Koontz,
None;
R. W. Burlingame,
None;
D. Lacomis,
None;
C. V. Oddis,
Genentech and Biogen IDEC Inc.,
.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hydroxy-3-methylglutaryl-coenzyme-a-reductase-hmgcor-antibody-in-necrotizing-myopathy-and-the-role-of-statins/