endocrine and metabolic disorders
Amyloidosis
Treatment of Amyloidosis
Supportive care Type-specific treatment There are specific treatments for most forms of amyloidosis, although some therapies are investigational. For all forms of systemic amyloidosis, supportive care measures can help relieve symptoms and improve quality of life. Supportive care measures are directed at the affected organ system: Patients with Overview of Nephrotic Syndrome and edema should be treated with salt and fluid restriction, and loop diuretics; because of the ongoing protein loss, protein intake should not be restricted. Patients with Overview of Cardiomyopathies should be treated with salt and fluid restriction and loop diuretics. Other medications for Gastrointestinal:Patients with diarrhea may benefit fromloperamide. Those with early satiety and gastric retention may benefit frommetoclopramide. In patients with Peripheral Neuropathy , Orthostatic Hypotension None For AL amyloidosis: Prompt initiation of anti-plasma cell therapy is essential to preserve organ function and prolong life. Most medications used for Treatment have been used in AL amyloidosis; choice of medication, dose, and schedule often must be modified when organ function is impaired. , combined with autologous Hematopoietic Stem Cell Transplantation can be highly effective in selected patients ( ) showed an unprecedented high rate of hematologic response ( Treatment references ). Hematologic response is based on monoclonal protein in serum and urine levels determined by immunofixation electrophoresis and serum light chain levels with kappa/lambda ratios. However, long-term survival data are lacking. All available treatments target clonal B-cells or plasma cells in AL amyloidosis. Studies of antifibril antibodies, such as birtamimab and CAEL-101, are in progress ( Treatment references ). Localized AL amyloidosis can be treated with low-dose external beam radiation therapy because plasma cells are highly radiosensitive. For ATTR amyloidosis: Liver transplantation Tetramer-stabilizing medications Gene silencing medications Liver Transplantation —which replaces the primary site of synthesis of the mutant protein with a new organ producing normal TTR—can be effective in certain ( Treatment references ). gene silencing using anti-sense RNA or RNA interference to block translation of TTR mRNA efficiently reduces serum levels of TTR, improves neurologic outcomes in about 50% of patients, and, in some patients, appears capable of repairing injured nerves ( Treatment references ). The gene silencing medications, , a second-generation gene silencer,demonstrated improved functional outcomes in patients with familial amyloid polyneuropathy ( Treatment references ). Preliminary data from another trial suggests that gene silencers may be effective in the treatment of cardiomyopathy in patients with ATTR amyloidosis ( For ATTRwt amyloidosis: Tetramer-stabilizing medications , in patients with ATTR or ATTRwt amyloid cardiomyopathy has been shown to decrease all-cause mortality and cardiovascular-related hospitalizations ( Treatment references ). Clinical trials are underway examining the effect of TTR gene silencers on the cardiomyopathy that occurs in patients with ATTRwt amyloidosis as well as the cardiomyopathy that occurs in patients with ATTR amyloidosis characterized by the mutant protein ( Unlike hereditary ATTR amyloidosis, liver transplantation is not effective for patients with ATTRwt because the amyloidogenic protein is a structurally normal TTR. For AA amyloidosis caused by familial Mediterranean fever, oralcolchicineis effective. For other AA types, treatment is directed at the underlying infection, inflammatory disease, or cancer. Colchicineor anti-IL1, anti-IL6, or anti-TNF medications may be used to interrupt the cytokine signaling, diminishing the inflammatory process driving hepatic production of serum amyloid A (SAA). 1.Sanchorawala V, Sun F, Quillen K, et al: Long-term outcome of patients with AL amyloidosis treated with high-dosemelphalanand stem cell transplantation: 20-year experience.Blood126: 2345–2347, 2015. doi: 10.1182/blood-2015-08-662726 2.Kastritis E, Palladini G, Minnema MC, et al:Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.N Engl J Med385(1):46-58, 2021. doi:10.1056/NEJMoa2028631 3.Quarta CC, Fontana M, Damy T, et al: Changing paradigm in the treatment of amyloidosis: From disease-modifying drugs to anti-fibril therapy.Front Cardiovasc Med9:1073503, 2022. doi:10.3389/fcvm.2022.1073503 4.Berk JL, Suhr OB, Obici L, et al: Repurposingdiflunisalfor familial amyloid polyneuropathy: a randomized clinical trial.JAMA310: 2658–2667, 2013. doi: 10.1001/jama.2013.283815 5.Maurer MS, Schwartz JH, Gundapaneni B, et al:Tafamidistreatment for patients with transthyretin amyloid cardiomyopathy.N Engl J Med379:1007–1016, 2018. 6.Adams D, Gonzalez-Duarte A, O'Riordan WD, et al:Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis.N Engl J Med379:11–21, 2018. 7.Benson MD, Waddington-Cruz M, Berk JL, et al:Inotersentreatment for patients with transthyretin amyloidosis.N Engl J Med379:22–31, 2018. 8.Adams D, Tournev IL, Taylor MS, et al: Efficacy and safety ofvutrisiranfor patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial.Amyloid30(1):1-9, 2023. doi:10.1080/13506129.2022.2091985 9.Maurer MS, Fontanta MA, Berk JL, et al: Primary results from APOLLO-B, a phase 3 study ofpatisiranin patients with transthyretin-mediated amyloidosis with cardiomyopathy. Abstract presented at International Symposium of Amyloidosis, September 2022,Heidelberg Germany. 10.Writing Committee, Kittleson MM, Ruberg FL, et al: 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee [published correction appears inJ Am Coll Cardiol81(11):1135, 2023].J Am Coll Cardiol81(11):1076-1126, 2023. doi:10.1016/j.jacc.2022.11.022 