Use of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Statin‐Associated Immune‐Mediated Necrotizing Myopathy: A Case Series

Abstract

Objective. To determine the safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with statin-associated anti-3-hydroxy-3-methlyglutaryl coenzyme A reductase (anti-HMGCR)-positive immunemediated necrotizing myopathy (IMNM).Methods. Muscle strength was assessed in anti-HMGCR-positive patients at each visit before and after initiation of PCSK9 inhibitors. The trends in creatine kinase (CK) levels and serum anti-HMGCR antibody titers were monitored over time.Results. Among 122 anti-HMGCR-positive patients, we identified 8 patients who were receiving PCSK9 inhibitors for hyperlipidemia. Patients were followed up for an average of 1.5 years (range 3-37 months), and none exhibited reduction in muscle strength. The mean ± SD CK level prior to the initiation of PCSK9 inhibitors was 956 ± 1,137 IU/ liter, which was reduced to 419 ± 393 IU/liter at their last visit. Anti-HMGCR antibody titers followed a similar trend. Notably, in 2 patients, the initiation of the lipid-lowering medication was followed by unanticipated spontaneous clinical improvement and reduction in immunosuppression.Conclusion. PCSK9 inhibitors are safe for long-term use as a cholesterol-lowering agent in patients with statinassociated IMNM.

Immune Mediated Necrotizing Myopathy: A Rare Complication of Statin Therapy

“… 18 Cycles of every 2 weeks to 4 weeks have been reported during maintenance therapy, and can be stopped and tapered as tolerated. 19 …”

“…Statin rechallenge with the same or a different statin has shown to be largely unsuccessful and often results in disease flare up. 19 , 6 A recent case series at Johns Hopkins University found that PCSK9 inhibitors were well tolerated in 7 out of 8 patients with a previous history of statin-induced IMNM. 19 As a result PCSK9 may be an alternative medication for patients with high cardiovascular risk and IMNM.…”

“… 19 , 6 A recent case series at Johns Hopkins University found that PCSK9 inhibitors were well tolerated in 7 out of 8 patients with a previous history of statin-induced IMNM. 19 As a result PCSK9 may be an alternative medication for patients with high cardiovascular risk and IMNM. However, data is limited, thus highlighting an area requiring further research.…”

Statin-Induced Autoimmune Myopathy

“…She improved with steroids and her symptoms were minimal on follow-up. As far as alternative options for cholesterol management in patients with SAAM, we can consider PCSK9 inhibitors such as Praluent (alirocumab) and Repatha (evolocumab) [15].…”

Secondary Causes of Myositis

“…For patients with anti-HMGCR antibodies, cessation of statin therapy is important [ 54 ]. For patients that require cholesterol-lowering medication, proprotein convertase subtilisin/kexin type 9 (PCSK9) can be considered, as these medications were shown to be safe in a case series of 8 patients with HMGCR antibody-positive necrotizing myopathies [ 55 ]. In rare mild cases, further treatment beyond statin cessation may not be necessary [ 54 ].…”