Amyloidosis medical therapy: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Amyloidosis}} | {{Amyloidosis}} | ||
{{CMG}} {{ | {{CMG}}; {{AE}} {{shyam}} | ||
==Overview== | ==Overview== | ||
There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further organ damage and correcting the effects of [[organ failure]]. | There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further [[Organ (anatomy)|organ]] damage and correcting the effects of [[organ failure]]. | ||
==Medical Therapy== | ==Medical Therapy== | ||
=== Primary Amyloidosis (AL): === | |||
Some patients with primary [[amyloidosis]] respond to [[chemotherapy]] focused on the abnormal [[plasma cell]]s. A [[stem cell transplant]] may be done, as in [[multiple myeloma]]. | Some patients with primary [[amyloidosis]] respond to [[chemotherapy]] focused on the abnormal [[plasma cell]]s. A [[stem cell transplant]] may be done, as in [[multiple myeloma]]. | ||
*The initial | *The initial step in the treatment of this disorder is to correct the [[organ failure]], since the disease is discovered at an advanced stage when multiple [[organ systems]] may be affected. | ||
**[[Nephrotic syndrome]] is treated using supportive therapy and [[diuretics]]. | **[[Nephrotic syndrome]] is treated using supportive therapy and [[diuretics]]. | ||
**[[Renal failure]] is treated with [[dialysis]]. | **[[Renal failure]] is treated with [[dialysis]]. | ||
**[[Heart failure]] is treated using [[diuretics]]. | **[[Heart failure]] is treated using [[diuretics]]. | ||
**Gastrointestinal and nerve involvement are treated symptomatically. | **[[Gastrointestinal tract|Gastrointestinal]] and [[nerve]] involvement are treated [[Symptomatic|symptomatically]]. | ||
The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.<ref name="pmid29854961">{{cite journal| author=Milani P, Merlini G, Palladini G| title=Novel Therapies in Light Chain Amyloidosis. | journal=Kidney Int Rep | year= 2018 | volume= 3 | issue= 3 | pages= 530-541 | pmid=29854961 | doi=10.1016/j.ekir.2017.11.017 | pmc=5976806 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29854961 }} </ref> | |||
The most commonly used regimen for AL [[amyloidosis]] is CyBorD, which consists of [[cyclophosphamide]], [[bortezomib]], and [[dexamethasone]].<ref name="pmid29854961">{{cite journal| author=Milani P, Merlini G, Palladini G| title=Novel Therapies in Light Chain Amyloidosis. | journal=Kidney Int Rep | year= 2018 | volume= 3 | issue= 3 | pages= 530-541 | pmid=29854961 | doi=10.1016/j.ekir.2017.11.017 | pmc=5976806 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29854961 }} </ref> | |||
{| | {| | ||
| valign="top" | | | valign="top" | | ||
|+ | |+ | ||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Therapy}} | ! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Therapy}} | ||
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Mechanism of Action}} | ! style="background: #4479BA; width: 400px;" |{{fontcolor|#FFF|Mechanism of Action}} | ||
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Dosing}} | ! style="background: #4479BA; width: 400px;" |{{fontcolor|#FFF|Dosing}} | ||
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Adverse Effects}} | ! style="background: #4479BA; width: 400px;" |{{fontcolor|#FFF|Adverse Effects}} | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
Bortezomib | [[Bortezomib]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Reversibly inhibits the 26S proteasome, preventing recycling of proteins and inducing cell cycle arrest and apoptosis | *Reversibly inhibits the 26S [[proteasome]], preventing recycling of [[proteins]] and inducing [[cell cycle]] arrest and [[apoptosis]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Cycles 1-4: 1.3mg/m2 IV/SC on days 1, 4, 8, 11, 22, 25, 29, 32 | *Cycles 1-4: 1.3mg/m2 [[Intravenous|IV]]/[[Subcutaneous|SC]] on days 1, 4, 8, 11, 22, 25, 29, 32 | ||
*Cycles 5-9: 1.3mg/m2 IV/SC on days 1, 8, 22, 29 | *Cycles 5-9: 1.3mg/m2 [[Intravenous|IV]]/[[Subcutaneous|SC]] on days 1, 8, 22, 29 | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Peripheral neuropathy, VZV reactivation, hepatic impairment, asthenia, diarrhea, nausea, constipation, arthralgia, edema, dizziness | [[Peripheral neuropathy]], [[Varicella zoster virus|VZV]] reactivation, [[hepatic impairment]], [[asthenia]], [[diarrhea]], [[nausea]], [[constipation]], [[arthralgia]], [[edema]], [[dizziness]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
Dexamethasone | [[Dexamethasone]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Suppresses polymorphonuclear leukocytes | *Suppresses [[polymorphonuclear leukocytes]] | ||
*Inhibits prostaglandins and proinflammatory cytokines | *Inhibits [[prostaglandins]] and [[proinflammatory]] [[cytokines]] | ||
*Suppresses lymphocyte proliferation | *Suppresses [[lymphocyte]] proliferation | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*40mg PO weekly | *40mg [[Oral|PO]] weekly | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Infections, immunosuppression, bone loss, cataract formation, glaucoma, muscular atrophy | [[Infections]], [[immunosuppression]], [[bone loss]], [[cataract]] formation, [[glaucoma]], [[muscular]] [[atrophy]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Melphalan | [[Melphalan]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Inhibits DNA and RNA synthesis | *Inhibits [[DNA]] and [[RNA]] synthesis | ||
*Crosslinks DNA and causes DNA replication failure | *[[Crosslinking of DNA|Crosslinks DNA]] and causes [[DNA replication]] failure | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*6mg PO daily for 2-3 weeks, OR | *6mg [[Oral|PO]] daily for 2-3 weeks, OR | ||
*10mg PO daily for 7-10 days, OR | *10mg [[Oral|PO]] daily for 7-10 days, OR | ||
*0.15mg/kg daily PO for 7 days, THEN | *0.15mg/kg daily [[Oral|PO]] for 7 days, THEN | ||
*1-3mg or 0.05mg/kg PO daily after counts recover | *1-3mg or 0.05mg/kg [[Oral|PO]] daily after counts recover | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Myelosuppression, nausea, vomiting, pulmonary fibrosis, stomatitis | [[Myelosuppression]], [[nausea]], [[vomiting]], [[pulmonary fibrosis]], [[stomatitis]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Cyclophosphamide | [[Cyclophosphamide]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*Alkylating agent | *[[Alkylating agent]] | ||
*Crosslinks DNA and causes DNA replication failure | *[[Crosslinking of DNA|Crosslinks DNA]] and causes [[DNA replication]] failure | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*40-50mg/kg weekly | *40-50mg/kg weekly | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Myelosuppression, nausea, vomiting, hemorrhagic cystitis, secondary malignancies | [[Myelosuppression]], [[nausea]], [[vomiting]], [[hemorrhagic cystitis]], secondary [[malignancies]] | ||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | ||
Patisiran | [[Patisiran]]<ref name="pmid28893208">{{cite journal| author=Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J et al.| title=Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. | journal=BMC Neurol | year= 2017 | volume= 17 | issue= 1 | pages= 181 | pmid=28893208 | doi=10.1186/s12883-017-0948-5 | pmc=5594468 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28893208 }} </ref> | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*RNA interference therapy | *[[RNA interference]] therapy | ||
*Inhibits hepatic synthesis of transthyretin | *Inhibits [[hepatic]] synthesis of [[transthyretin]] | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
*0.3mg/kg | *0.3mg/kg weekly | ||
| style="padding: 5px 5px; background: #F5F5F5;" | | | style="padding: 5px 5px; background: #F5F5F5;" | | ||
Dyspepsia, dyspnea, erythema, bronchitis, blurry vision | [[Dyspepsia]], [[dyspnea]], [[erythema]], [[bronchitis]], [[blurry vision]] | ||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" | | |||
[[Daratumumab]]<ref name="pmid26864107">{{cite journal| author=van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK et al.| title=Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. | journal=Immunol Rev | year= 2016 | volume= 270 | issue= 1 | pages= 95-112 | pmid=26864107 | doi=10.1111/imr.12389 | pmc=4755228 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26864107 }} </ref> | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Anti-CD38 monoclonal antibody | |||
*Depletes B lymphocytes and plasma cells | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*16mg/kg weekly for weeks 1-8, then every 2 weeks for weeks 9-24, then every 4 weeks thereafter | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
[[Anemia]], [[neutropenia]], [[false positive]] [[Indirect Coombs test|indirect Coomb's test]], [[infusion reaction]], [[lymphopenia]] | |||
|- | |- | ||
|} | |} | ||
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Treatment options with limited success include [[melphalan]], [[prednisone]], and [[colchicine]]. | Treatment options with limited success include [[melphalan]], [[prednisone]], and [[colchicine]]. | ||
=== Secondary Amyloidosis (AA): === | |||
* Medical or surgical treatment of the underlying chronic infection or inflammatory disease is recommended among all patients who develop AA amyloidosis. | |||
* Aggressively treating the disease that is causing the excess [[amyloid]] protein can improve [[symptoms]] and slow down or halt the progression of the disease. | |||
* Complications such as [[heart failure]], [[renal failure]], and other problems can sometimes be treated, when needed. | |||
*Although the choice of therapy depends on the underlying cause of chronic inflammation, the aim is always to suppress production of SAA to within the normal range. | |||
*Examples of treatments for the commonest disorders underlying AA amyloidosis:<ref name="pmid30274625">{{cite journal| author=Papa R, Lachmann HJ| title=Secondary, AA, Amyloidosis. | journal=Rheum Dis Clin North Am | year= 2018 | volume= 44 | issue= 4 | pages= 585-603 | pmid=30274625 | doi=10.1016/j.rdc.2018.06.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30274625 }} </ref> | |||
{| | |||
| valign="top" | | |||
|+ | |||
! style="background: #4479BA;" |{{fontcolor|#FFF|Underlying Condition}} | |||
! style="background: #4479BA;" |{{fontcolor|#FFF|Treatment Options}} | |||
! style="background: #4479BA;" |{{fontcolor|#FFF|Examples}} | |||
|- | |||
| rowspan="3" style="padding: 5px 5px; background: #DCDCDC;" |Inflammatory arthritis | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Conventional disease-modifying agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Gold | |||
*Hydroxychloroquine sulfasalazine | |||
*Azathioprine | |||
*Methotrexate | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Other immunosuppressant agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Cyclosporine | |||
*Cyclophosphamide | |||
*Mycophenolate | |||
*Leflunomide | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Biologic agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Infliximab | |||
*Etanercept | |||
*Adalimumab | |||
*Tocilizumab | |||
*Rituximab | |||
|- | |||
| rowspan="3" style="padding: 5px 5px; background: #DCDCDC;" |Periodic fevers | |||
| style="padding: 5px 5px; background: #F5F5F5;" | On-demand agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Nonsteroidal anti-inflammatory drugs | |||
*Prednisone | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Colchicine (for familial mediterranean fever) | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Colchicine | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Biologic agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Anakinra | |||
*Canakinumab | |||
|- | |||
| rowspan="5" style="padding: 5px 5px; background: #DCDCDC;" |Inflammatory bowel disease | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Conventional disease-modifying agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Sulfasalazine | |||
*Mesalazine | |||
*Azathioprine | |||
*Methotrexate | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Biologic agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Infliximab | |||
*Adalimumab | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Antibiotics | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Metronidazole | |||
*Ciprofloxacin | |||
*Azithromycin | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Biologic agents | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Infliximab | |||
*Adalimumab | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Surgery | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
ileo-cecal resection and primary reconstruction | |||
|- | |||
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Immunodeficiency | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Immunoglobulins | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
* | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Antibiotics | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Cotrimoxazole | |||
*Miconazole | |||
|- | |||
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Chronic infections | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Antibiotics and surgery | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
* | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Physiotherapy (in case of bronchiectasis) | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
* | |||
|- | |||
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Immunodeficiency | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Immunoglobulins | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
* | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Antibiotics | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
*Cotrimoxazole | |||
*Miconazole | |||
|- | |||
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" | Neoplasia | |||
| style="padding: 5px 5px; background: #F5F5F5;" | Chemotherapy and surgery | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Varies according to type of cancer | |||
|- | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
Biologic agents (in Castleman disease) | |||
| style="padding: 5px 5px; background: #F5F5F5;" | | |||
* Tocilizumab | |||
|- | |||
|} | |||
* Long-term inflammatory control can be accompanied by gradual regression of amyloid deposits and improvement in renal function. | |||
*Currently a second clinical trial is in progress in order to evaluate a targeted inhibitor molecule, Kiacta, in the management of secondary amyloidosis. | |||
*Novel therapies aimed at promoting clearance of existing amyloid deposits soon may be an effective treatment approach. | |||
=== Wild-Type or Senile Amyloidosis (ATTRwt): === | |||
* Treatment is generally aimed at the symptoms of wild-type ATTR amyloidosis, such as treating amyloid deposits in the heart. | |||
**Because the heart is the most commonly affected organ, your disease will be monitored and treated by a cardiologist. | |||
*For some patients with severe wild-type (senile) ATTR amyloidosis, a heart transplant may be the best option. Stanford is one of the world's leading centers for heart transplantation for amyloidosis. | |||
*In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo.<ref name="pmid30145929">{{cite journal| author=Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M et al.| title=Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. | journal=N Engl J Med | year= 2018 | volume= 379 | issue= 11 | pages= 1007-1016 | pmid=30145929 | doi=10.1056/NEJMoa1805689 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30145929 }}</ref> | |||
*In ATTRwt amyloidosis, therapy is supportive, but both for this disease and for ATTR, pharmacologic therapies aimed at stabilizing the transthyretin molecule and thus preventing amyloid formation are being actively investigated. | |||
=== Familial Amyloidosis (ATTR): === | |||
* The optimal therapy for familial amyloidosis is removal of the source of abnormal TTR production. | |||
**The liver is the dominant source of transthyretin; hence, in patients with less advanced disease, liver transplant may be performed. | |||
**Patients with severe heart involvement may benefit from a heart transplant. | |||
* In addition, multiple clinical trials are now testing medications that may slow or halt progression of familial ATTR amyloidosis. | |||
**Tafamidis is a drug recently approved for familial amyloid polyneuropathy (FAP) in Europe.<ref name="pmid301459292">{{cite journal| author=Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M et al.| title=Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. | journal=N Engl J Med | year= 2018 | volume= 379 | issue= 11 | pages= 1007-1016 | pmid=30145929 | doi=10.1056/NEJMoa1805689 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30145929 }}</ref> | |||
***This agent is being tested in ongoing trials for other forms of ATTR. | |||
**Patisiran and Inoteresen are TTR gene silencers. Recently FDA approved their use for ATTRm amyloidosis with peripheral neuropathy.<ref name="pmid29972757">{{cite journal| author=Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK et al.| title=Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. | journal=N Engl J Med | year= 2018 | volume= 379 | issue= 1 | pages= 22-31 | pmid=29972757 | doi=10.1056/NEJMoa1716793 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29972757 }}</ref> | |||
*Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members. | |||
<br /> | |||
=== '''Dialysis-related amyloidosis ('''β2-microglobulin) === | |||
* There is no specific medical treatment for DRA. | |||
* However, removal of significant amounts of beta2-microglobulin (beta2-m) may prevent or slow progression of the disease. | |||
* This can be accomplished best by kidney transplantation. | |||
* Other treatment opitons include: | |||
** Hemodialysis with a biocompatible high-flux dialysis membrane, hemodiafiltration | |||
** The use of ultrapure dialysate | |||
** A beta2-m adsorbent column may also result in lowering the level of beta2-microglobulin. | |||
* Kidney transplantation is considered the definitive treatment for DRA in patients with end-stage renal disease. | |||
== References == | == References == |
Latest revision as of 18:02, 30 October 2019
Amyloidosis Microchapters |
Diagnosis |
---|
Treatment |
Case Studies |
Amyloidosis medical therapy On the Web |
American Roentgen Ray Society Images of Amyloidosis medical therapy |
Risk calculators and risk factors for Amyloidosis medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]
Overview
There are few available treatments for primary amyloidosis. Since the disease is typically discovered at an advanced stage, the initial treatment is aimed at preventing further organ damage and correcting the effects of organ failure.
Medical Therapy
Primary Amyloidosis (AL):
Some patients with primary amyloidosis respond to chemotherapy focused on the abnormal plasma cells. A stem cell transplant may be done, as in multiple myeloma.
- The initial step in the treatment of this disorder is to correct the organ failure, since the disease is discovered at an advanced stage when multiple organ systems may be affected.
- Nephrotic syndrome is treated using supportive therapy and diuretics.
- Renal failure is treated with dialysis.
- Heart failure is treated using diuretics.
- Gastrointestinal and nerve involvement are treated symptomatically.
The most commonly used regimen for AL amyloidosis is CyBorD, which consists of cyclophosphamide, bortezomib, and dexamethasone.[1]
Treatment options with limited success include melphalan, prednisone, and colchicine.
Secondary Amyloidosis (AA):
- Medical or surgical treatment of the underlying chronic infection or inflammatory disease is recommended among all patients who develop AA amyloidosis.
- Aggressively treating the disease that is causing the excess amyloid protein can improve symptoms and slow down or halt the progression of the disease.
- Complications such as heart failure, renal failure, and other problems can sometimes be treated, when needed.
- Although the choice of therapy depends on the underlying cause of chronic inflammation, the aim is always to suppress production of SAA to within the normal range.
- Examples of treatments for the commonest disorders underlying AA amyloidosis:[4]
Underlying Condition | Treatment Options | Examples |
---|---|---|
Inflammatory arthritis | Conventional disease-modifying agents |
|
Other immunosuppressant agents |
| |
Biologic agents |
| |
Periodic fevers | On-demand agents |
|
Colchicine (for familial mediterranean fever) |
Colchicine | |
Biologic agents |
| |
Inflammatory bowel disease | Conventional disease-modifying agents |
|
Biologic agents |
| |
Antibiotics |
| |
Biologic agents |
| |
Surgery |
ileo-cecal resection and primary reconstruction | |
Immunodeficiency | Immunoglobulins |
|
Antibiotics |
| |
Chronic infections | Antibiotics and surgery |
|
Physiotherapy (in case of bronchiectasis) |
| |
Immunodeficiency | Immunoglobulins |
|
Antibiotics |
| |
Neoplasia | Chemotherapy and surgery |
Varies according to type of cancer |
Biologic agents (in Castleman disease) |
|
- Long-term inflammatory control can be accompanied by gradual regression of amyloid deposits and improvement in renal function.
- Currently a second clinical trial is in progress in order to evaluate a targeted inhibitor molecule, Kiacta, in the management of secondary amyloidosis.
- Novel therapies aimed at promoting clearance of existing amyloid deposits soon may be an effective treatment approach.
Wild-Type or Senile Amyloidosis (ATTRwt):
- Treatment is generally aimed at the symptoms of wild-type ATTR amyloidosis, such as treating amyloid deposits in the heart.
- Because the heart is the most commonly affected organ, your disease will be monitored and treated by a cardiologist.
- For some patients with severe wild-type (senile) ATTR amyloidosis, a heart transplant may be the best option. Stanford is one of the world's leading centers for heart transplantation for amyloidosis.
- In patients with transthyretin amyloid cardiomyopathy, tafamidis was associated with reductions in all-cause mortality and cardiovascular-related hospitalizations and reduced the decline in functional capacity and quality of life as compared with placebo.[5]
- In ATTRwt amyloidosis, therapy is supportive, but both for this disease and for ATTR, pharmacologic therapies aimed at stabilizing the transthyretin molecule and thus preventing amyloid formation are being actively investigated.
Familial Amyloidosis (ATTR):
- The optimal therapy for familial amyloidosis is removal of the source of abnormal TTR production.
- The liver is the dominant source of transthyretin; hence, in patients with less advanced disease, liver transplant may be performed.
- Patients with severe heart involvement may benefit from a heart transplant.
- In addition, multiple clinical trials are now testing medications that may slow or halt progression of familial ATTR amyloidosis.
- Genetic counseling is recommended for individuals with hereditary amyloidosis and their family members.
- There is no specific medical treatment for DRA.
- However, removal of significant amounts of beta2-microglobulin (beta2-m) may prevent or slow progression of the disease.
- This can be accomplished best by kidney transplantation.
- Other treatment opitons include:
- Hemodialysis with a biocompatible high-flux dialysis membrane, hemodiafiltration
- The use of ultrapure dialysate
- A beta2-m adsorbent column may also result in lowering the level of beta2-microglobulin.
- Kidney transplantation is considered the definitive treatment for DRA in patients with end-stage renal disease.
References
- ↑ Milani P, Merlini G, Palladini G (2018). "Novel Therapies in Light Chain Amyloidosis". Kidney Int Rep. 3 (3): 530–541. doi:10.1016/j.ekir.2017.11.017. PMC 5976806. PMID 29854961.
- ↑ Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J; et al. (2017). "Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy". BMC Neurol. 17 (1): 181. doi:10.1186/s12883-017-0948-5. PMC 5594468. PMID 28893208.
- ↑ van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK; et al. (2016). "Monoclonal antibodies targeting CD38 in hematological malignancies and beyond". Immunol Rev. 270 (1): 95–112. doi:10.1111/imr.12389. PMC 4755228. PMID 26864107.
- ↑ Papa R, Lachmann HJ (2018). "Secondary, AA, Amyloidosis". Rheum Dis Clin North Am. 44 (4): 585–603. doi:10.1016/j.rdc.2018.06.004. PMID 30274625.
- ↑ Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M; et al. (2018). "Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy". N Engl J Med. 379 (11): 1007–1016. doi:10.1056/NEJMoa1805689. PMID 30145929.
- ↑ Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M; et al. (2018). "Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy". N Engl J Med. 379 (11): 1007–1016. doi:10.1056/NEJMoa1805689. PMID 30145929.
- ↑ Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK; et al. (2018). "Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis". N Engl J Med. 379 (1): 22–31. doi:10.1056/NEJMoa1716793. PMID 29972757.