A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients.

OBJECTIVE: To determine if proinflammatory and prothrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. METHODS: Four groups of patients (age 18-65) were recruited: (a) primary antiphospholipid syndrome; (b) systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS) (SLE/APS); (c) persistent aPL positivity without SLE or APS (Primary aPL); and (d) persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for 3 months. At 3 months, patients stopped the study medication and they were followed for another 3 months. Blood samples for 12 proinflammatory and prothrombotic biomarkers were collected monthly for 6 months. RESULTS: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin (IL)-6, IL1ß, vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α, interferon (IFN)-α, inducible protein-10 (IP10), soluble CD40 ligand (sCD40L), soluble tissue factor (sTF) and intracellular cellular adhesion molecule (ICAM)-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1ß, VEGF, TNFα, IP10, sCD40L and sTF). CONCLUSIONS: Our prospective mechanistic study demonstrates that proinflammatory and prothrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients.

Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Idiopathic Inflammatory Myopathy: From Mechanisms of Action to Clinical Applications.

Idiopathic inflammatory myopathies (IIMs) result in proximal muscle weakness and other intramuscular and extramuscular manifestations. Pharmacologic treatments in use for IIMs are limited to corticosteroids and immunosuppressants in addition to supportive physical and occupational therapy. Glucagon-like peptide-1 receptor (GLP-1R) agonists are currently utilized in the treatment of type II diabetes and obesity but may play a role in the treatment of IIMs. The current scoping review of extant literature aims to synthesize findings from studies assessing the therapeutic effects of GLP-1R agonists in the management of inflammatory myopathy and muscle atrophy. A literature search was conducted through PubMed, resulting in a total of 19 research-based articles included in this review. Mice and human studies showed, with varying levels of significance, that GLP-1R agonists led to decreases in muscle atrophy, inflammation, adiposity, and weakness; improvement in muscle microvasculature and endurance; and promotion of muscle mitochondria biogenesis. The potential for GLP-1R agonists to improve muscle function and architecture underscores the need for large randomized controlled, clinically comparative trials of GLP-1R agonists in patients with IIM.