Objective: To evaluate clinical associations of anti-hydroxy-3-methylglutaryl-coenzyme A
reductase (anti-HMGCR) antibody (Ab) and
statin exposure in necrotizing
myopathy (NM) patients. Methods: NM without a known
myositis-specific
autoantibody (MSA) was ascertained from a large single-centre
myositis database between 1985 and 2012. A comparison NM cohort included 32 anti-SRP+
autoantibody patients, and other control groups included 74 non-NM
myositis patients and 21 non-
myositis controls. Sera from all cases and controls were tested using a validated anti-HMGCR
enzyme-linked
immunosorbent assay. Clinical features including
statin use and anti-HMGCR Ab status were compared between cases and controls. Results: Of the 256 NM muscle biopsies reviewed, only 48 subjects with available sera were identified as traditional MSA-negative NM. Anti-HMGCR positivity was significantly (p < 0.001) associated with MSA-negative NM [48% (23/48)] compared to all of the
myositis and non-
myositis controls [5% (6/127)]. Most anti-HMGCR Ab-positive NM patients had high titres of anti-HMGCR (83%) and a history of
statin exposure (78%), along with severe
muscle weakness, high
creatine kinase (CK) levels (90% ≥ 5000 IU/L), a paucity of other organ manifestations, and the need for immunosuppression with
prednisone and
methotrexate, but generally favourable outcomes. Anti-HMGCR serum levels were associated with baseline CK levels but not
muscle weakness. Conclusion: HMGCR Ab-positive NM patients are associated with
statin exposure, have severe
muscle weakness and high CK at presentation, lack other organ manifestations, and generally have favourable outcomes from immunosuppression. Anti-HMGCR Abs should be assessed in MSA-negative NM patients, particularly those with a history of
statin exposure.