{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:29:46Z","timestamp":1784680186976,"version":"3.55.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005609","name":"University of Turku","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005609","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Rheumatol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The use of statins, which are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) enzyme, may in rare cases be associated with immune-mediated necrotizing myopathy. This condition is characterized by the presence of autoantibodies directed against the HMGCR enzyme. Previously considered very rare, the incidence of this myopathy diagnosis has markedly increased in our rheumatology unit over the past years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of 13 patients diagnosed with statin-associated anti-HMGCR antibody (Ab)-positive immune-mediated necrotizing myopathy (anti-HMGCR-IMNM) over the 5-year period (June 2020\u2013May 2025) at the Turku University Hospital\u2019s rheumatology department serving 490,000 inhabitants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients presented with elevated creatine kinase (CK) levels, positive anti-HMGCR-Ab, proximal muscle weakness, and the initial symptom was usually difficulty walking. No other myositis autoantibodies were detected and extra-myopathic symptoms were rare. Most patients responded to immunosuppressive therapy including glucocorticoids, methotrexate or azathioprine, and rituximab with a more severe disease course. Disease severity ranged from mild to fatal. The incidence of statin-associated anti-HMGCR-IMNM was 5.3 cases per million per year, approximately 2.75 per 100,000 statin users per year, higher than previously reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Statin-associated anti-HMGCR-IMNM is a rare but increasingly recognized condition requiring early diagnosis and immunosuppressive treatment. The clinical presentation is highly variable. Treatment and its intensity must be tailored individually, taking into account the patient\u2019s comorbidities and treatment related risks.<\/jats:p>\n                    <jats:p>\n                      <jats:table-wrap>\n                        <jats:table>\n                          <jats:tbody>\n                            <jats:tr>\n                              <jats:td align=\"left\" colspan=\"2\">\n                                <jats:bold>Key Points<\/jats:bold>\n                                \u2022\n                                <jats:italic>Anti-HMGCR antibody\u2013positive immune-mediated necrotizing myopathy (anti-HMGCR-IMNM) may be triggered by statins, one of the most commonly prescribed classes of medications. Because delayed diagnosis may lead to significant morbidity, it is important that clinicians are familiar with this rare myopathic disorder.<\/jats:italic>\n                                \u2022\n                                <jats:italic>Previously, statin-associated anti-HMGCR-IMNM was considered a very rare diagnosis. However, the incidence of this diagnosis appears to have increased markedly over recent years.<\/jats:italic>\n                                \u2022\n                                <jats:italic>The apparent increase in diagnoses may be attributable to the growing use of statins; additionally, improved recognition and awareness of the disease may also partially explain this rise.<\/jats:italic>\n                                \u2022\n                                <jats:italic>Rituximab may be an alternative in selected cases where the disease course is neither rapidly progressive nor life-threatening, although further research is needed.<\/jats:italic>\n                              <\/jats:td>\n                            <\/jats:tr>\n                          <\/jats:tbody>\n                        <\/jats:table>\n                      <\/jats:table-wrap>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10067-026-08136-5","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:35:26Z","timestamp":1777458926000},"page":"3517-3524","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Increasing recognition of statin-associated anti-HMGCR antibody\u2013positive autoimmune myopathy: a single-center retrospective study"],"prefix":"10.1007","volume":"45","author":[{"given":"Mikko","family":"Mali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Piril\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Jokela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tero","family":"P\u00e4\u00e4kk\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-4785","authenticated-orcid":false,"given":"Markku","family":"Mali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"8136_CR1","doi-asserted-by":"publisher","first-page":"4995","DOI":"10.1093\/rheumatology\/keaf238","volume":"64","author":"T Khoo","year":"2025","unstructured":"Khoo T, Tan E, Limaye V, Gunawardena H, Sadler R, Lamb J (2025) The incidence of anti-HMGCR immune-mediated necrotizing myopathy: an Australian and UK retrospective multi-site cohort study. Rheumatology 64:4995\u20135003. https:\/\/doi.org\/10.1093\/rheumatology\/keaf238","journal-title":"Rheumatology"},{"key":"8136_CR2","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/S0140-6736(22)01545-8","volume":"400","author":"Cholesterol Treatment Trialists\u2019 Collaboration","year":"2022","unstructured":"Cholesterol Treatment Trialists\u2019 Collaboration (2022) Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet 400:832\u2013845. https:\/\/doi.org\/10.1016\/S0140-6736(22)01545-8","journal-title":"Lancet"},{"key":"8136_CR3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/mus.23854","volume":"5","author":"P Mohassel","year":"2013","unstructured":"Mohassel P, Mammen AL (2013) Anti-HMGCR myopathy. J Neuromuscul Dis 5:11\u201320. https:\/\/doi.org\/10.1002\/mus.23854","journal-title":"Anti-HMGCR myopathy J Neuromuscul Dis"},{"key":"8136_CR4","doi-asserted-by":"publisher","first-page":"483","DOI":"10.2147\/TCRM.S197941","volume":"16","author":"E Tiniakou","year":"2020","unstructured":"Tiniakou E (2020) Statin-associated autoimmune myopathy: current perspectives. Ther Clin Risk Manag 16:483\u2013492. https:\/\/doi.org\/10.2147\/TCRM.S197941","journal-title":"Ther Clin Risk Manag"},{"key":"8136_CR5","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1097\/BOR.0000000000000832","volume":"33","author":"T Kurashige","year":"2021","unstructured":"Kurashige T (2021) Anti-HMGCR myopathy: clinical and histopathological features, and prognosis. Curr Opin Rheumatol 33:554\u2013562. https:\/\/doi.org\/10.1097\/BOR.0000000000000832","journal-title":"Curr Opin Rheumatol"},{"key":"8136_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103468","volume":"22","author":"T Khoo","year":"2023","unstructured":"Khoo T, Chinoy H (2023) Anti-HMGCR immune-mediated necrotising myopathy: addressing the remaining issues. Autoimmun Rev 22:103468. https:\/\/doi.org\/10.1016\/j.autrev.2023.103468","journal-title":"Autoimmun Rev"},{"key":"8136_CR7","doi-asserted-by":"publisher","unstructured":"Dalakas MC (2020) Inflammatory myopathies: update on diagnosis, pathogenesis and therapies, and COVID-19-related implications. Acta Myol 39:289\u2013301. https:\/\/doi.org\/10.36185\/2532-1900-032","DOI":"10.36185\/2532-1900-032"},{"key":"8136_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2024-005007","volume":"11","author":"AM Kerola","year":"2025","unstructured":"Kerola AM, Pietik\u00e4inen A, Barantseva J, Pajander A, H\u00e4nninen A (2025) Predictive value of myositis antibodies: role of semiquantitative classification and positivity for more than one autoantibody. RMD Open 11:e005007. https:\/\/doi.org\/10.1136\/rmdopen-2024-005007","journal-title":"RMD Open"},{"key":"8136_CR9","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/acr.20035","volume":"62","author":"LG Rider","year":"2010","unstructured":"Rider LG, Koziol D, Giannini EH, Jain MS, Smith MR, Whitney-Mahoney K (2010) Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies. Arthritis Care Res (Hoboken) 62:465\u2013472. https:\/\/doi.org\/10.1002\/acr.20035","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"8136_CR10","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/1477-7525-1-20","volume":"30","author":"B Bruce","year":"2003","unstructured":"Bruce B, Fries JF (2003) The Stanford Health Assessment Questionnaire (HAQ): a review of its history, issues, progress and documentation. J Rheumatol 30:167\u2013168. https:\/\/doi.org\/10.1186\/1477-7525-1-20","journal-title":"J Rheumatol"},{"key":"8136_CR11","unstructured":"Kela F (2024) Suomen l\u00e4\u00e4ketilasto 2023 [Finnish Medicines Statistics 2023]. Helsinki: Finnish Medicines Agency Fimea; Available from: https:\/\/urn.fi\/URN:NBN:fi-fe20241217103868.\u00a0Accessed 20 Mar 2026"},{"key":"8136_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102993","volume":"21","author":"G Merlonghi","year":"2022","unstructured":"Merlonghi G, Antonini G, Garibaldi M (2022) Immune-mediated necrotizing myopathy (IMNM): a myopathological challenge Autoimmun Rev 21 102993https:\/\/doi.org\/10.1016\/j.autrev.2021.102993","journal-title":"Autoimmun Rev"},{"key":"8136_CR13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1080\/03009742.2023.2289729","volume":"53","author":"M Mali","year":"2024","unstructured":"Mali M, Piril\u00e4 L, Perander L, Gardberg M, Jokela M (2024) Identical twins with statin-associated anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibody-positive autoimmune myopathy. Scand J Rheumatol 53:81\u201382","journal-title":"Scand J Rheumatol"},{"key":"8136_CR14","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1007\/s40674-021-00174-1","volume":"7","author":"E Weeding","year":"2021","unstructured":"Weeding E, Tiniakou E (2021) Therapeutic management of immune-mediated necrotizing myositis. Curr Treat Options Rheumatol 7:150\u2013160","journal-title":"Curr Treat Options Rheumatol"},{"key":"8136_CR15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13075-019-2093-6","volume":"22","author":"A Meyer","year":"2020","unstructured":"Meyer A, Troyanov Y, Drouin J, Oligny-Longpr\u00e9 G, Landon-Cardinal O, Hoa S (2020) Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients. Arthritis Res Ther 22:5","journal-title":"Arthritis Res Ther"},{"key":"8136_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2023.105932","volume":"92","author":"R Campanilho-Marques","year":"2025","unstructured":"Campanilho-Marques R, Fonseca JE, Machado PM (2025) Treatment of idiopathic inflammatory myopathies. Joint Bone Spine 92:105932. https:\/\/doi.org\/10.1016\/j.jbspin.2023.105932","journal-title":"Joint Bone Spine"},{"key":"8136_CR17","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/mus.28333","volume":"71","author":"J Suh","year":"2025","unstructured":"Suh J, Amato AA (2025) Effectiveness and safety of IVIG for the treatment of HMGCR immune-mediated necrotizing myopathy. Muscle Nerve 71:392\u2013397","journal-title":"Muscle Nerve"},{"key":"8136_CR18","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.1093\/rheumatology\/keaf116","volume":"64","author":"J Paik","year":"2025","unstructured":"Paik J, Werth V, Chinoy H, Masri K, Jambekar A (2025) Treatment guideline for idiopathic inflammatory myopathies in adults: a comparative review Rheumatology 64:3288\u20133302","journal-title":"Rheumatology"},{"key":"8136_CR19","first-page":"231","volume":"3","author":"SP Silva","year":"2025","unstructured":"Silva SP, Eugenio G, Pinto M, Barcelos A (2025) Clinical and persistent remission in anti-HMGCR immune-mediated necrotizing myopathy to single cycle of rituximab \u2013 a case-based review. ARP Rheumatol 3:231\u2013236","journal-title":"ARP Rheumatol"},{"key":"8136_CR20","unstructured":"Lundberg I, Jin T, Martineus C, O\u2019Rourke D, Skoglund E et\u202fal (2025) Behandling av manifestationer vid myosit [Management of manifestations in myositis]. Available from: https:\/\/riktlinjer.svenskreumatologi.se\/riktlinjer-och-rekommendationer\/behandling-av-manifestationer-vid-myosit\/.\u00a0Accessed 20 Mar 2026"}],"container-title":["Clinical Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10067-026-08136-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10067-026-08136-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10067-026-08136-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:25:38Z","timestamp":1780982738000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10067-026-08136-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["8136"],"URL":"https:\/\/doi.org\/10.1007\/s10067-026-08136-5","relation":{},"ISSN":["0770-3198","1434-9949"],"issn-type":[{"value":"0770-3198","type":"print"},{"value":"1434-9949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"23 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"This was a non-interventional retrospective study without direct patient contact. According to Finnish legislation, no patient consent or ethical committee approval was required. Permissions for the study were obtained from the Wellbeing Services County of Southwest Finland (VARHA Research Permit T1148\/2025; VARHA Information Permit 2025\u20131157-TL).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All authors have reviewed and approved the final version of the manuscript, confirming the accuracy and integrity of the work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}