Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions

Mahmud Mahamid1,3, Reuven Mader4, Rifaat Safadi1,2 1Liver Unit, Holy Family Hospital, Nazareth, Israel; 2Hadassah Medical Center, Jerusalem, Israel; 3Shaare Zedek Medical Center, Jerusalem, Israel; 4Rheumatology Unit, Ha&rsquo;emek Medical Center, Afula, Israel Background: Elevation of liver...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mahamid M, Mader R, Safadi R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2ff58f96397e4eb1b71e8d44f2d418f2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2ff58f96397e4eb1b71e8d44f2d418f2
record_format	dspace
spelling	oai:doaj.org-article:2ff58f96397e4eb1b71e8d44f2d418f22021-12-02T01:06:30ZHepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions1179-1438https://doaj.org/article/2ff58f96397e4eb1b71e8d44f2d418f22011-10-01T00:00:00Zhttp://www.dovepress.com/hepatotoxicity-of-tocilizumab-and-anakinra-in-rheumatoid-arthritis-man-a8408https://doaj.org/toc/1179-1438Mahmud Mahamid1,3, Reuven Mader4, Rifaat Safadi1,2 1Liver Unit, Holy Family Hospital, Nazareth, Israel; 2Hadassah Medical Center, Jerusalem, Israel; 3Shaare Zedek Medical Center, Jerusalem, Israel; 4Rheumatology Unit, Ha&rsquo;emek Medical Center, Afula, Israel Background: Elevation of liver enzymes in rheumatoid arthritis patients treated with tocilizumab (Actemra&reg;) or anakinra (Kineret&reg;) is a well-documented phenomenon. However, characterization of liver histology has not been defined in most cases. Similarly, the factors involved in decisions regarding discontinuation of treatment and outcome have not been discussed in the literature to any significant extent. Cases: Two women with rheumatoid arthritis refractory to standard therapies are reported here. One was treated with tocilizumab and the other with anakinra, and both developed toxic liver effects. Liver biopsy in both cases showed focal necrosis of hepatocytes &ndash; a hallmark of drug toxicity &ndash; with steatosis and early fibrosis. Inflammatory infiltrates were prominent in the patient treated with anakinra but not in the tocilizumab-treated patient. However, FibroTest (Assistance publique &ndash; H&ocirc;pitaux de Paris, Paris, France) in the latter patient showed an inflammatory activity of A2 and was staged as F2, and the histology also showed hemorrhagic areas. Although both patients were overweight and both had been exposed to steroids, the steatosis and steatohepatitis were considered to be related to drug hepatotoxicity. Other possible etiologies for liver injury were excluded. Discontinuation of anakinra led to rapid normalization of liver enzymes. The patient receiving tocilizumab developed hepatosplenomegaly but had normal liver enzymes. In spite of the hepatosplenomegaly, the tocilizumab treatment was continued since the patient had not responded to other drugs. There was a good response to the tocilizumab treatment and the liver biopsy showed only insignificant, reversible liver injury. At follow-up at 6-months the patient remains stable. Conclusion: As cases showing tocilizumab or anakinra liver toxicity are appearing more frequently to the authors, a full assessment for liver injury is recommended in patients given those drugs, with careful consideration of the decision to continue or discontinue treatment. Further studies with long-term follow-up analysis are mandatory to guide appropriate management strategies. Keywords: anakinra, interleukin receptors, liver injury, rheumatoid arthritis, tocilizumabMahamid MMader RSafadi RDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2011, Iss default, Pp 39-43 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Mahamid M Mader R Safadi R Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
description	Mahmud Mahamid1,3, Reuven Mader4, Rifaat Safadi1,2 1Liver Unit, Holy Family Hospital, Nazareth, Israel; 2Hadassah Medical Center, Jerusalem, Israel; 3Shaare Zedek Medical Center, Jerusalem, Israel; 4Rheumatology Unit, Ha&rsquo;emek Medical Center, Afula, Israel Background: Elevation of liver enzymes in rheumatoid arthritis patients treated with tocilizumab (Actemra&reg;) or anakinra (Kineret&reg;) is a well-documented phenomenon. However, characterization of liver histology has not been defined in most cases. Similarly, the factors involved in decisions regarding discontinuation of treatment and outcome have not been discussed in the literature to any significant extent. Cases: Two women with rheumatoid arthritis refractory to standard therapies are reported here. One was treated with tocilizumab and the other with anakinra, and both developed toxic liver effects. Liver biopsy in both cases showed focal necrosis of hepatocytes &ndash; a hallmark of drug toxicity &ndash; with steatosis and early fibrosis. Inflammatory infiltrates were prominent in the patient treated with anakinra but not in the tocilizumab-treated patient. However, FibroTest (Assistance publique &ndash; H&ocirc;pitaux de Paris, Paris, France) in the latter patient showed an inflammatory activity of A2 and was staged as F2, and the histology also showed hemorrhagic areas. Although both patients were overweight and both had been exposed to steroids, the steatosis and steatohepatitis were considered to be related to drug hepatotoxicity. Other possible etiologies for liver injury were excluded. Discontinuation of anakinra led to rapid normalization of liver enzymes. The patient receiving tocilizumab developed hepatosplenomegaly but had normal liver enzymes. In spite of the hepatosplenomegaly, the tocilizumab treatment was continued since the patient had not responded to other drugs. There was a good response to the tocilizumab treatment and the liver biopsy showed only insignificant, reversible liver injury. At follow-up at 6-months the patient remains stable. Conclusion: As cases showing tocilizumab or anakinra liver toxicity are appearing more frequently to the authors, a full assessment for liver injury is recommended in patients given those drugs, with careful consideration of the decision to continue or discontinue treatment. Further studies with long-term follow-up analysis are mandatory to guide appropriate management strategies. Keywords: anakinra, interleukin receptors, liver injury, rheumatoid arthritis, tocilizumab
format	article
author	Mahamid M Mader R Safadi R
author_facet	Mahamid M Mader R Safadi R
author_sort	Mahamid M
title	Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
title_short	Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
title_full	Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
title_fullStr	Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
title_full_unstemmed	Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
title_sort	hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/2ff58f96397e4eb1b71e8d44f2d418f2
work_keys_str_mv	AT mahamidm hepatotoxicityoftocilizumabandanakinrainrheumatoidarthritismanagementdecisions AT maderr hepatotoxicityoftocilizumabandanakinrainrheumatoidarthritismanagementdecisions AT safadir hepatotoxicityoftocilizumabandanakinrainrheumatoidarthritismanagementdecisions
_version_	1718403306919821312

Hepatotoxicity of tocilizumab and anakinra in rheumatoid arthritis: management decisions

Ejemplares similares