Session Information
Date: Sunday, October 21, 2018
Title: Muscle Biology, Myositis and Myopathies Poster I: Clinical Features and Disease Course
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Immune-mediated necrotising myopathy (IMNM) is characterised by paucity of inflammation on muscle biopsy and is associated with antibodies to signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). IMNM patients tend to be more refractory to conventional immunosuppressive therapies. Previous case series suggested that a more severe clinical course and greater resistance to treatment in anti-SRP myopathy compared to anti-HMGCR. Thus, we aimed to analyse disease characteristics and treatment responses in a single-centre IMNM cohort based on SRP or HMGCR antibody status.
Methods:
All subjects with a diagnosis of IMNM from 2008 to 2017 were included in this retrospective study. Patient electronic records were reviewed and disease subgroups based on antibody status (anti-SRP and anti-HMGCR) were analysed.
Results:
|
Subgroup |
HMGCR |
SRP |
|
Number of patients, n (%) |
17 (61) |
11 (39) |
|
Female, n (%) |
13 (76) |
6 (55) |
|
Median age at onset, years (Interquartile range) |
62 (57 – 71) |
52 (31 – 55) |
|
Ethnicity, n (%) |
White British 12 (70.6) African-Caribbean 2 (11.8) South Asian 2 (11.8) Chinese 1 (5.8) |
African 8 (72.7) African-Caribbean 2 (18.2) White British 1 (9.1) |
|
Median peak creatine kinase, units/L (Interquartile range) |
7030 (4143 – 19114) |
9750 (3237 – 19022) |
|
Statin exposure, n (%) |
14 (82) |
1 (9) |
|
Type 2 diabetes, n (%) |
11 (65) |
0 (0) |
|
Cardiac involvement, n (%) |
0/5 (0) |
2/6 (33) |
|
Malignancy, n (%) |
2 (12) |
1 (9) |
|
Rituximab, n (%) |
2 (12) |
5 (46) |
28 patients had a diagnosis of IMNM, of which 39% had anti-SRP and 61% had anti-HMGCR myopathy. SRP patients were predominantly of African or African-Caribbean descent (91%) with more ethnic heterogeneity observed in the HMGCR group. 82% of HMGCR patients were exposed to statins compared to 9% of SRP subjects. Six SRP patients underwent cardiac MRI with two patients demonstrating cardiac involvement whilst myocarditis was not identified in anti-HMGCR myopathy. Two HMGCR patients were identified with malignancies (follicular thyroid carcinoma and low-grade non-Hodgkin’s lymphoma) and one SRP patient was identified with prostate adenocarcinoma.
11 HMGCR and 4 SRP patients were initiated on ‘triple therapy’ – pulsed intravenous methylprednisolone (IVMP) followed by high dose oral prednisolone, intravenous immunoglobulin (IVIg) and an immunosuppressant (methotrexate or azathioprine). The remainder were initially commenced on either IVMP/prednisolone or IVIg dependent on patient factors (e.g. diabetes).
46% of SRP patients received rituximab therapy (6 months to 9 years post symptom onset) compared to 12% of HMGCR patients (4 to 6 years post symptom onset). 3 SRP patients responded well to rituximab clinically and biochemically (the other 2 patients were followed-up in local hospitals after their first dose of rituximab).
Conclusion:
There were distinct features in our IMNM cohort based on antibody profile. Anti-SRP myopathy disproportionately affected more African and African-Caribbean patients. This group tended to have higher creatine kinase levels and cardiac complications were present in some. Anti-SRP myopathy was associated with a failure to respond adequately to conventional therapies requiring the addition of rituximab more frequently and earlier in the disease course. There is heterogeneity in therapy choice depending on clinician experience and patient factors suggesting the need for further prospective studies and standardised protocols.
To cite this abstract in AMA style:
Yeoh SA, Thomas R, Baldeweg F, Alkoky H, Shipa M, Badrulhisham F, Tahir H, Donnelly S, Pakozdi A, Fattah Z, Radunovic A. Comparison of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme Α Reductase and Anti-Signal Recognition Particle Necrotising Myopathies: A Single Centre Experience [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/comparison-of-anti-3-hydroxy-3-methylglutaryl-coenzyme-%ce%b1-reductase-and-anti-signal-recognition-particle-necrotising-myopathies-a-single-centre-experience/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-anti-3-hydroxy-3-methylglutaryl-coenzyme-%ce%b1-reductase-and-anti-signal-recognition-particle-necrotising-myopathies-a-single-centre-experience/