Ipilimumab-induced toxicities and the gastroenterologist.
J Gastroenterol Hepatol
; 30(4): 657-66, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25641691
ABSTRACT
Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis. To date, the recommendations for managing irAEs secondary to ipilimumab have been steroids at a moderate dose of prednisolone (1 mg/kg) as well as immunosuppressive agents such as mycophenolate mofetil (MMF) for steroid-refractory hepatitis and infliximab in the management of corticosteroid-refractory colitis. However, the dosing and the duration of immunosuppressive therapy have not been systematically studied in the setting of treating ipilimumab-induced irAEs. Therefore, additional immune-modifying agents and/or a change in dosing may be required to manage severe irAEs unresponsive to existing treatment recommendations. We describe a treatment paradigm illustrated by a series of five patients who experienced irAEs. In three cases of metastatic melanoma, ipilimumab-induced hepatitis was successfully treated with high-dose parenteral pulsed methylprednisolone. In two other melanoma patients with ipilimumab-induced colitis, one patient had satisfactory resolution of his colitis with high-dose corticosteroid therapy alone and the other patient required infliximab infusion. We have reviewed the current literature and management algorithms for ipilimumab-induced irAEs. Treatment options and the rationale for their use are discussed, including the use of pulsed high-dose steroids, MMF, azathioprine and calcineurin inhibitors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Doença Hepática Induzida por Substâncias e Drogas
/
Imunossupressores
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Melanoma
/
Anticorpos Monoclonais
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
J Gastroenterol Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Austrália