Ab0870 anti-hmgcr autoantibody levels in the follow-up of statin-induced immune-mediated necrotizing myopathy. multicentric study of 24 patients

Background Statin-induced immune-mediated necrotizing myopathy (IMNM) is associated with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies. It is characterized by elevated creatine kinase (CK) levels, and severe muscle weakness. Measuring disease activity is problematic, since it is challenging to differentiate it from damage. The utility of the quantitative analysis of anti-HMGCR autoantibodies during the follow-up has not been thoroughly studied. Objectives To assess the usefulness of measuring the levels of anti-HMGCR autoantibodies in relation to response to treatment. Methods We included patients all consecutive patients diagnosed with statin-induced IMNM according to the definition of the European Neuromuscular International Workshop 2016 (1) and positivity for anti-HMGCR autoantibodies in two centers from Spain and Sweden from January 2017 to November 2022. All patients were followed for at least 3 months to be included. Clinical data was extracted retrospectively from the patients’ clinical records. Remission was defined as no disease activity assessed by expert rheumatologists according to 2016 ACR/EULAR response criteria in myositis. Moderate and high disease activity was defined when physician global activity score was higher than 2 or 3 (on a Likert scale) respectively [2,3]. Anti-HMGCR autoantibodies level was measured at the time of diagnosis and at a variable period of time after treatment. Results were obtained using the chemiluminescence immunoassay (CLIA) method. Negative anti-HMGCR was considered as levels lower than 20 U/ml. Results Our group combined of 24 patients. Main features of the patients are summarized in the TABLE 1 . 21 (87.5%) patients reached clinical remission or low disease activity. However, 3 patients (12.5%) remained with moderate activity of the disease. None of the patients had high disease activity. Anti-HMGCR levels at diagnosis were higher than 100 U/ml in 23 patients (95.8%) and above 200 in 11 patients (45.8%). However, anti-HMGCR levels after treatment were significantly lower in patients in remission (p=0.035). Numeric levels in patients at diagnosis of the disease and after treatment are shown in the FIGURE 1 . Most of the patients at diagnosis (with high activity of the disease) had high anti-HMGCR levels (22 patients, 91.7% had levels above 100 U/ml). After treatment, most patients in remission had low (n=3, 14.3%) or negative (n=9, 42.9%), while patients with moderate activity had higher levels (n=2, 66.7% with levels above 100 U/ml). However, 6 patients in remission (28.6%) still had levels above 100 U/ml. Conclusion Anti-HMGCR autoantibodies levels evaluation can be used in parallel with other tools to accurately measure disease activity in patients with statin-induced IMNM. However, more studies are needed to confirm these results. References [1]Allenbach Y et al. Neuromuscul Disord. 2018;28(1):87-99 [2]Rider LG et al., Ann Rheum Dis. 2017 May;76(5):782-791. doi: 10.1136/annrheumdis-2017-211401. Erratum in: Ann Rheum Dis. 2018 Apr;77(4):623 [3]Rider LG, et al. Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11(0 11):S118-57. Table 1. General features of 24 patients diagnosed with anti-HMGCR positive IMNM Variables Total (n=24) Remission/ low activity (n=21) Moderate activity (n=3) P (remission vs no remission) Age (years), mean ± SD 68.2 ± 7.2 67.6 ± 7.1 67.3 ± 10.1 0.95 Sex (women), n (%) 10 (42) 9 (42.9) 1 (33.3) 0.89 Analytical values, mean ±SD CK (ukat/L) at diagnosis 114.3 ± 103.9 103.5 ± 100 230.7 ± 84.5 0.51 Anti-HMGCR levels at diagnosis 214.6 ± 110.8 212.2 ± 89.7 295 ± 127.8 0.24 Anti-HMGCR levels after treatment 83.8 ± 89 74 ± 80.4 190 ± 100.1 0.035* Muscle strength assessment, mean ±SD MMT-8 at diagnosis 64.4 ± 12 65.4 ± 12.7 62.7 ± 12.5 0.73 MMT-8 after treatment 77.6 ± 4.2 78.6 ± 3.1 74.3 ± 8.1 0.1 CK: Creatine kinase. Upper limit for CK: < 4.7 ukat/L for men and 3.5 ukat/L for women. *: p < 0.05 Figure 1. Anti-HMGCR autoantibodies levels according to disease activity after treatment in 24 patients with IMNM. LDA: Low disease activity Acknowledgements: NIL. Disclosure of Interests David Martínez-López: None declared, Diana Prieto-Peña Grant/research support from: UCB, Roche, Pfizer, Amgen, Janssen, AbbVie/Abbott, Novartis, Eli Lilly, Cristina Corrales-Selaya: None declared, Piotr Szczęsny: None declared, Antonella Notarnicola: None declared, Marcos López Hoyos: None declared, Ricardo Blanco Grant/research support from: RB received grants/research supports from AbbVie, MSD, and Roche, had consultation fees/participation in company-sponsored speaker’s bureau from AbbVie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD and received support for attending meetings and/or travel from AbbVie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD., Ingrid E. Lundberg Grant/research support from: Argenx, AstraZeneca, Bristol Myers Squibb, Novartis, Corbus, EMD Serono, Roche, Pfizer, Orphazyme, Octapharma, Kezar, Janssen, Maryam Dastmalchi: None declared.