Browse the corpus

Inotersen is an antisense oligonucleotide indicated for the treatment of polyneuropathy in patients with hereditary transthyretin-mediated amyloidosis (hATTR). hATTR is a rare and severe condition caused by a TTR mutation that leads to misfolded transthyretin protein deposition in various tissues, including the peripheral nervous system, heart, kidneys, and eyes. This deposition results in progressive damage, particularly affecting the nervous system, and leads to polyneuropathy, which significantly impacts quality of life. Inotersen inhibits the synthesis of transthyretin, which helps slow disease progression. The drug is administered subcutaneously and has been shown to improve symptoms and delay deterioration in patients with hATTR. Monitoring for adverse effects, such as thrombocytopenia and renal toxicity, is crucial for patient safety. Understanding the role of inotersen in managing hATTR helps optimize therapeutic strategies and improve outcomes for patients with this debilitating disease. Objectives: Identify patients with polyneuropathy secondary to hATTR who may benefit from inotersen therapy. Determine the appropriate preventative or management measures to address the adverse reactions associated with inotersen administration. Assess the contraindications for inotersen therapy. Implement strategies for improving coordination between healthcare providers to improve the treatment of patients with polyneuropathy caused by hATTR. Access free multiple choice questions on this topic.

Inotersen toxicity may cause glomerulonephritis and renal failure in some patients. Additionally, patients with pre-existing renal conditions may experience exacerbated symptoms.[11][12] Inotersen may result in hepatotoxicity, as the liver is an organ where antisense oligonucleotide accumulation may occur. Due to a lack of research in this domain, it is currently unknown whether inotersen is toxic in pregnancy. Additionally, with the exception of previously described rare occurrences, current data supports inotersen use for up to 5 years without significant toxicity concerns, as long as bloodwork is monitored accordingly and contraindications are avoided.[10] Documentation regarding acute inotersen toxicity and antidotes in such circumstances is scarce. Should patients undergoing inotersen therapy experience severe adverse effects, therapy may be discontinued.

Managing hATRR with inotersen therapy requires qualified healthcare practitioners working as a coordinated interprofessional healthcare team to provide optimal patient care. Healthcare providers should also be cognizant of potential risks of inotersen use, especially in populations with pre-existing conditions such as those patients with renal or liver dysfunction. Inotersen should not be administered to patients with a platelet count below 100,000/μL, a history of glomerulonephritis with previous inotersen use, or hypersensitivity reactions to inotersen. Prescribers should be aware that TEGSEDI is only available in the USA via a risk evaluation and mitigation strategy (REMS), a restricted distribution channel named "TEGSEDI REMS Program." Clinicians should inform patients of the risks of serious bleeding caused by severe thrombocytopenia and glomerulonephritis. Qualified healthcare professionals can train patients and caregivers on safe administration techniques if self-administration is desired for initial or subsequent dosing. Additionally, clinicians should assess patients before treatment to ensure that eGFR, UPCR, AST, and bilirubin are within appropriate ranges. Close monitoring of platelet count, serum creatinine, eGFR, urinalysis, UPCR, ALT, AST, and total bilirubin is recommended during and up to 8 weeks after therapy to ensure patient safety. Healthcare providers must work in unison to communicate these salient concerns to prevent adverse reactions and poor healthcare outcomes. Inotersen appears to be a relatively safe drug with a low toxicity profile, which can be used to manage polyneuropathy in patients with hATTR. When used properly, inotersen can effectively and safely manage patients experiencing the neuropathic manifestations of hATTR for at least 5 years.[10][13]