Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Jun 2019
ReviewClinical pharmacology of caplacizumab for the treatment of patients with acquired thrombotic thrombocytopenic purpura.
Introduction: Caplacizumab is a humanized anti-von Willebrand Factor (vWF) Nanobody® for the treatment of acquired Thrombotic Thrombocytopenic Purpura (aTTP). Caplacizumab targets the A1-domain of vWF, inhibiting the interaction between vWF and platelets. Clinical studies conducted in aTTP patients confirmed the rapid and sustained complete suppression of the vWF activity using an initial intravenous dose of 10 mg, and a maintenance subcutaneous 10 mg daily dosing regimen, with corresponding favorable efficacy and safety profiles. ⋯ Renal and hepatic impairment are not expected to influence the exposure to the drug, and no direct or indirect drug-drug pharmacokinetic interactions are anticipated based on the mechanism of action and the specificity of the pharmacodynamic effect of caplacizumab. Expert opinion: Caplacizumab prevents the interaction between vWF and platelets, offering a direct and rapid therapeutic intervention to stop microthrombosis. The combination of caplacizumab with plasma exchange and immunosuppression represents an important, potentially life-saving advance in the treatment of aTTP patients.
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Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient's own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys. Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells). The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects.. ⋯ These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.