To establish safety of alternative cholesterol lowering therapy, and usefulness of monitoring anti-HMGCR titres in HMGCR myopathy.

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.

We performed a retrospective study at our tertiary neuromuscular centre. All patients presenting with a myopathy and positive anti-HMGCR from 2010-2023 were included.

39 patients were included in the analysis.

Ethnically, the majority of patients were white (27/39), and 61% female. Comorbidities included type-2 diabetes mellitus (67%), and hypertension (59%). Median age of onset was 66 (IQR 11). 3 patients were statin-naïve at presentation.

Median creatinine kinase (CK) at presentation was 8122 units/L (IQR 5338-14000).

Alternative cholesterol lowering therapy commenced included ezetimibe (n=18), and PCSK9 inhibitors (n=3), with no progression of disease.

79% were treated with prednisolone. Methotrexate (59%) and IVIg (49%) were the commonest disease modifying immunosuppression used often in combination with prednisolone. 4 patients required treatment re-escalation after disease remission, while 9 patients remain off immunosuppression.  21% were treated with rituximab, and 2 patients with abatacept.

Where available, anti-HMGCR titres correlated significantly with CK levels (r=0.689, p<0.001). Where >1 HMGCR titre is available, 8/14 reduced over time, and of those, 5/8 corresponded to a meaningful improvement in CK, while 2 patients had an improving CK, with a stable HMGCR titre. 4/14 patients are in remission off all immunosuppression, of which 2 had HMGCR titres below the threshold of positivity, and 2 had falling titres.

We demonstrate that remission off immunosuppression in anti-HMGCR myopathy is achievable, and anti-HMGCR titres have potential to support immunosuppression withdrawal. We show alternative cholesterol lowering therapy is safe, and not associated with worsening disease.