P145 Single-centre experience of managing patients with anti-HMGCR antibody immune-mediated necrotizing myopathy

Abstract

Abstract Background/Aims Anti-HMGCR antibodies are associated with a rare form of immune mediated necrotizing myopathy. Statin exposure is common, but statin-naïve presentations can occur. Given its rarity, optimal treatment regimes, alternative cholesterol lowering therapy, and implications of monitoring antibody titre have yet to be established. Methods A retrospective single-centre study was carried out at our tertiary neuromuscular clinic. All patients with a positive anti-HMGCR antibody presenting with a myopathy from 2010-2023, seen in the neuromuscular clinic at the Royal London Hospital, were included. Data on demographics, investigations, and treatments were recorded. Results In total, 39 patients were included in the analysis. Within the anti-HMGCR cohort, ethnically the largest proportion were white (27/39), followed by Asian (n = 7), and four patients black/black-African. 61% of patients were female. The commonest comorbidities were type 2 diabetes mellitus (67%), and hypertension (59%). Median age of onset was 66 (IQR 11). Three patients had no known statin exposure prior to disease onset, of which one had a limb-girdle muscular dystrophy distribution of muscle involvement. Median creatinine kinase (CK) at presentation was 8122 units/L (IQR 5338-14000). Alternative cholesterol lowering therapy was successfully commenced with ezetimibe (n = 18), or PCSK9 inhibitors (n = 3), with no progression of disease. Five malignancies were reported: one breast Ca, one tubo-ovarian, two thyroid, and one low grade NHL. None of the patients had cardiac involvement. 79% of patients were treated with prednisolone. Induction triple therapy of a steroid, IVIg and DMARD was used in 36% of patients. Methotrexate and IVIg were the commonest DMARDs used (59% and 54% respectively), often used in combination with prednisolone. Only four patients had a flare in disease requiring treatment re-escalation, nine patients are in remission off immunosuppression (Table 1). 21% were treated with rituximab, and two patients with abatacept. Where antibody titres were available, anti-HMGCR correlated significantly with CK levels (r = 0.689, p < 0.001). Of the patients with more than one HMGCR titre recorded, 8/14 reduced over time, and of those, 5/8 corresponded to a meaningful improvement in CK, while two patients had an improving CK, with a stable HMGCR titre. 4/14 patients are in remission off all immunosuppression, of which two of these had HMGCR titres below the threshold of positivity, and two had falling titres. Conclusion Anti-HMGCR IMNM remains rare. We demonstrate that remission off immunosuppression is achievable, and that anti-HMGCR titres may be of use to support immunosuppression withdrawal. We also show that, in this cohort of patients, alternative cholesterol lowering therapy is safe, and not associated with worsening disease. Disclosure K.E. Clark: None. R. Thomas: None. S. Kelly: None. L. Walker: None. A. Herrey: None. A. Dougan: None. R. Patel: None. S. Fhadil: None. A. Radunovic: None.