Ipilimumab-induced toxicities and the gastroenterologist

J Gastroenterol Hepatol. 2015 Apr;30(4):657-66. doi: 10.1111/jgh.12888.


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.

Keywords: CTLA-4 antibody; colitis; hepatitis; immunotherapy; ipilimumab; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Azathioprine / administration & dosage
  • Calcineurin Inhibitors / administration & dosage
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Colitis / chemically induced*
  • Colitis / drug therapy
  • Glucocorticoids / administration & dosage
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Infliximab / administration & dosage
  • Ipilimumab
  • Melanoma / drug therapy*
  • Melanoma / secondary*
  • Methylprednisolone / administration & dosage
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives
  • Patient Care Team
  • Prednisolone / administration & dosage
  • Pulse Therapy, Drug


  • Antibodies, Monoclonal
  • Calcineurin Inhibitors
  • Glucocorticoids
  • Immunosuppressive Agents
  • Ipilimumab
  • Prednisolone
  • Infliximab
  • Mycophenolic Acid
  • Azathioprine
  • Methylprednisolone