All the patients had significant muscle symptoms (muscle weakness and/or myalgia) and positive anti-HMGCR antibodies at diagnosis. an induction therapy combining IVIG with GCs and/or methotrexate to achieve persistent remission of the disease and steroid-free maintenance. Under IVIG-based regimens, clinical improvement and CK normalization occurred in more than two thirds of patients by six months. Relapse rate was low (3/16) and 2/3 relapses occurred after treatment suspension. Nearly 90% of the patients who successfully discontinued GCs were treated with a triple immunosuppressive regimen. In conclusion, an IVIG-based regimen, which particularly includes high-dose immunoglobulin, GCs TC-A-2317 HCl and methotrexate, can provide a fast remission achievement with GC saving. Keywords: anti-HMGCR antibody, autoimmune myopathy, immune-mediated necrotizing myopathy, statins 1. Introduction Statin-associated autoimmune myopathy is a relatively newly described disorder and the presence of autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) have only recently been identified [1,2]. Anti-HMGCR myopathy is a rare side effect of statin therapy, even though it can also develop in statin-na?ve patients [3,4,5]. Its incidence is not well defined, though it is estimated in approximately 2C3 of every 100,000 statin-treated patients [6,7]. It usually affects middle-aged people with some cardiovascular risk factors, such as type 2 diabetes, hypertension or hypercholesterolemia, which justify the introduction of statins [8]. The myopathy is characterized by symmetric muscle weakness, markedly elevated serum creatine kinase (CK) levels, abnormal electromyography (EMG) [9], and histologic evidence of muscle cell necrosis and degeneration, along with a lack of significant inflammatory infiltrates and circulating autoantibodies against 3-hydroxy-3-methylglutaryl coenzyme TC-A-2317 HCl A reductase (HMGCR) [7,10], which have been recognized as possible pathogenic autoantibodies [10,11]. Unlike other immune-mediated myopathies, there are few reports of extra-muscular involvement. Nevertheless, non-specific systemic and CTNND1 extra-muscular symptoms, such as arthritis, Raynauds phenomenon and rash, are uncommon [3]. A predisposing genetic background has been also documented, since anti-HMGCR myopathy has one of the strongest associations between an immunogenetic risk factor and autoimmune disease, in particular with the class II human leukocyte antigen (HLA) allele D related B (DRB)1*11:01 [12]. Despite statin discontinuation, anti-HMGCR myopathy can persist and require long-term immunosuppressive therapy [13]. The age at onset can influence the outcome, with younger patients having more severe muscle disease than older patients and a worse prognosis [14]. There are no guidelines for therapy, to date; however, some studies suggest that high-dose intravenous immunoglobulins (IVIG) could be a promising therapy, consistently with their efficacy in other autoimmune myositis [15], while glucocorticoids (GCs) may not be the cornerstone of this disease, differently from polymyositis [13]. The aim of the present study is to provide a further support to the prompted use of immunosuppressive IVIG-based treatment in anti-HMGCR myopathy. To this end, a retrospective analysis of a multi-center cohort of patients suffering from anti-HMGCR myopathy was carried out. Importantly, the patients were followed by different medical specialists, all of them concordant, aiming to reach a complete disease remission after induction therapy as a target of treatment, and a minimal use or avoidance of GCs during the following maintenance therapy. During the induction phase, all the participating centers used IVIG with or without methotrexate (MTX), in addition to GCs. The results reported here support the efficacy of the IVIG-based regimens, and, in particular, a triple-therapy induction strategy (high-dose IVIG, MTX, and GCs) for the anti-HMGCR myopathy. Moreover, this IVIG-based regimen minimized the use of GCs, in association with a steroid-sparing immunosuppressant (SSI), during the maintenance phase. 2. Experimental Section 2.1. Data Collection This is a retrospective study based on electronic clinical chart records. Consecutive patients TC-A-2317 HCl suffering from statin-associated autoimmune myopathy were collected in six Italian specialized centers between 2012 and 2019, from different specialties, i.e., Rheumatology, Allergy and Clinical Immunology, and Neurology. Data on demographics, statin use, myopathic features (i.e., clinical manifestations, serum CK levels, anti-HMGCR antibody at onset), and treatment strategies were collected. The Medical Research Council of Great Britain (MRC) muscle strength grading system was used to perform manual muscle testing (MMT) [16]. Clinical remission of disease was defined as the absence of muscle symptoms, recovered muscle strength based on MRC score evaluation, and normalization of serum CK levels. Clinical relapse was defined as the reappearance of muscle symptoms and worsening of muscle strength, and raise in serum CK levels beyond the upper limit defined by reference laboratories. The induction therapy was defined as the first chosen treatment from diagnosis to clinical remission. IVIG was given at the dose of.