Session Information
Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose:
There is a variable response rate to Intravenous immunoglobulin (IVIG) in patients with autoimmune myopathies. The aim of this study was to determine whether the presence of individual myositis-specific autoantibodies (MSA) predicts improved muscle strength in response to IVIG.
Methods:
A total of 378 adult subjects with a diagnosis of polymyositis or dermatomyositis based on the Bohan & Peter criteria, who presented to our Center between 2004 and 2014, had been treated with IVIG. Modified MRC scores for the 16 proximal muscle groups were summed to yield a composite score of muscle strength (range 0-160). The following groups of subjects were excluded from the study: those with minimal weakness at the initiation of IVIG therapy (composite score > 156/160) (n=30), those with inadequate data on the efficacy of IVIG including those who were on IVIG therapy at presentation to our Center (n=143), those with inadequate follow-up (<5 months) (n=57), patients who did not receive a standard dose (2 g/kg, given in 2-5 days/month, for a period of 3-6 months) (n=45), and patients for whom the existing therapies had been increased or a new medication had been added during IVIG therapy (n=36). All patients were tested for MSAs by three reference laboratories using previously validated immunoprecipitation methods. A positive response was defined by a ≥4 point increase in composite score. Fisher’s exact test was used to examine the effects of each MSA. Exact logistic regression was used to calculate the odds ratio.
Results:
Among the 67 subjects included in this study, 17 (25.4%) were non-responders and 50 (74.6%) were responders (Table 1). 54/67 (80.6%) of subjects had a detectable MSA. The response to IVIG was different between statin-exposed and statin-naïve anti-HMG-CoA reductase (HMGCR) subjects. All 14 (100%) statin-exposed anti-HMGCR+ patients responded but only 4 of 7 (57.1%) statin-naïve anti-HMGCR+ patients were responsive to IVIG (p=0.026) (Table2). Overall, anti-HMGCR in statin-exposed patients predicted a higher response rate to IVIG (p=0.014). In contrast, anti-SRP antibody was associated with lack of response (p=0.001). Of note, all anti-TIF-1γ positive patients responded to IVIG therapy (p=0.055). The odds ratio of response to IVIG was 8.8 (95%CI: 1.34 – [+infinity]) for anti-HMGCR+ and 0.04 (95%CI: 0-0.31) for anti-SRP positive patients.
Conclusion:
MSAs may predict a characteristic response to certain ISs. Our results indicate that while anti-SRP antibody predicts a poor response, statin-exposed anti-HMGCR+ patients are more likely to respond to IVIG therapy.
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Table 1- Demographics and baseline characteristics of the study patients |
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|
IVIG responder (n=50) |
IVIG non-responder (n=17) |
P Value |
|
Age at diagnosis, mean (SD), year |
52.3 (13.9) |
44.8 (12.8) |
0.054 |
|
Duration from onset of symptoms to initiation of IVIG therapy, median (Q1-Q3), month |
26 (6-41) |
13 (7-18) |
0.10 |
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Ethnicity (%) |
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|
|
|
White |
74.0 |
52.9 |
0.23 |
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African-American |
18.0 |
35.3 |
|
|
Othera |
8.0 |
11.8 |
|
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Male (%) |
30.0 |
23.5 |
0.76 |
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Malignancy (%) |
18.0 |
5.9 |
0.43 |
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Initial CPK, median (Q1-Q3) |
3500 (760- 11000) |
7000 (3000-13000) |
0.18 |
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Mean (SD) composite muscle strength at the beginning of IVIG therapy |
136.0 (14.9) |
143.2 (17.3) |
0.101 |
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Number of immunosuppressive medications prior to IVIG therapy, median (IQR) |
1 (1-3) |
2 (1-2) |
0.63 |
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Dysphagia (%) |
58.0 |
82.4 |
0.09 |
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Fever at onset (%) |
12.0 |
5.9 |
0.67 |
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Raynaud’s phenomenon (%) |
30.0 |
35.3 |
0.76 |
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Bohan & Peter classification (%) |
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|
|
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Dermatomyositis |
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|
0.58 |
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Definite |
40.0 |
23.5 |
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Probable |
10.0 |
11.8 |
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Possible |
6.0 |
0.0 |
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Polymyositis |
|
|
|
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Definite |
34.0 |
47.1 |
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Probable |
8.0 |
17.7 |
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Possible |
2.0 |
0.0 |
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Table2- Myositis-specific autoantibodies and IVIG response |
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Autoantibody |
IVIG responsive (%) n=50 |
IVIG non-responsive (%) n=17 |
P Value |
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HMGCR |
|
|
|
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Statin exposed |
14 (28.0) |
0 (0.0) |
0.014 |
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Statin unexposed |
4 (8.0) |
3 (17.7) |
0.36 |
|
SRP |
0 (0.0) |
5 (29.4) |
0.001 |
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Anti-synthetase a |
7 (14.0) |
4 (23.5) |
0.45 |
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NXP-2 |
2 (4.0) |
3 (17.7) |
0.099 |
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TIF-1γ |
10 (20.0) |
0 (0.0) |
0.055 |
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Mi-2 |
2 (4.0) |
0 (0.0) |
1.0 |
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MSA-negative b |
11 (22.0) |
2 (11.8) |
0.49 |
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a Anti-synthetase antibodies included anti-jo-1 (n=10) and anti-OJ (n=1) b Patients with a negative test for any of the following antibodies were considered MSA-negative: anti-HMGCR, anti-SRP, anti-NXP2, anti-TIF-1γ, anti-Mi2, anti-MDA5, and anti-synthetase autoantibodies (anti-Jo1, anti-EJ/OJ, anti-PL7/PL12)
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To cite this abstract in AMA style:
Lahoutiharahdashti A, Pinal-Fernandez I, Albayda J, Paik JJ, Danoff SK, Mammen A, Christopher-Stine L. Autoimmune Myopathies: Effects of Intravenous Immunoglobulin Therapy on Muscle Strength and Predictors of Response [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/autoimmune-myopathies-effects-of-intravenous-immunoglobulin-therapy-on-muscle-strength-and-predictors-of-response/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoimmune-myopathies-effects-of-intravenous-immunoglobulin-therapy-on-muscle-strength-and-predictors-of-response/