title: More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
abstract: To study disease severity and response to therapy in a large cohort of patients with anti-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)-associated myositis.
  
  
  
  Muscle strength, creatine kinase levels and treatments were assessed in anti-HMGCR-positive patients at each clinical visit. Univariate and multivariate analyses were used to analyse the influence of clinical characteristics on strength and the change in strength over time. Whole exome sequencing was performed in a subset of patients.
  
  
  
  . Among 50 patients followed for ⩾2 years, only 22 (44%) reached full strength with immunosuppressive therapy; even among those with full strength, 55% continued to have CK levels in excess of 500 IU/l and only three could be tapered off immunosuppressive therapy. Both univariate and multivariate analysis showed that patients who were older at disease onset were stronger at all time points (P < 0.001) and improved faster (P < 0.008) than younger patients; a history of statin exposure was not independently associated with the improvement rate. Younger patients were more likely to have refractory disease (P = 0.02) than older patients. Among eight refractory patients with DNA available for testing, whole exome sequencing did not reveal pathogenic mutations in known dystrophy genes. The risk of cancer was not increased in anti-HMGCR myositis patients compared with the general population.
  
  
  
  Anti-HMGCR myositis is usually a chronic disease requiring long-term immunosuppression. Although younger patients had more severe disease and a worse prognosis than older patients, they did not have evidence of a known co-existing muscular dystrophy to explain their persistent, and sometimes progressive, muscle weakness.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tiniakou
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Iago
authors.initials: I
authors.lastname: Pinal-Fernandez
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lloyd
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Jemima
authors.initials: J
authors.lastname: Albayda
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Julie
authors.initials: J
authors.lastname: Paik
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Jessie L
authors.initials: JL
authors.lastname: Werner
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda and.
authors.forename: Cassie A
authors.initials: CA
authors.lastname: Parks
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Christopher-Stine
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.|National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda and.|Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mammen
mesh_terms: D000293:Adolescent; D000328:Adult; D000359:Aftercare; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000378:metabolism; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000276:immunology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D053580:Muscle Strength / Q000276:immunology / Q000502:physiology; D018908:Muscle Weakness / Q000201:enzymology / Q000276:immunology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000276:immunology; D009220:Myositis / Q000201:enzymology* / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000201:enzymology / Q000276:immunology; D011379:Prognosis; D020127:Recovery of Function / Q000276:immunology / Q000502:physiology; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D006903:Hydroxymethylglutaryl CoA Reductases; D003402:Creatine Kinase
keywords: autoantibodies; myopathy; polymyositis