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Health Canada Endorsed Important Safety Information on Remicade (Infliximab)

Possible association of Remicade with hepatosplenic T-cell lymphoma in pediatric and young adult patients with Crohn's disease

Jul 27, 2006 | www.docguide.com

Centocor, Inc. and Schering Canada, Inc., in consultation with Health Canada, are informing health care professionals and the general public of important new safety information regarding Remicade (infliximab).

Remicade (infliximab) is a chimeric IgG monoclonal antibody known as a biological response modifier that is directed against the cytokine tumour necrosis factor-alpha (TNFalpha). It is indicated for the treatment of adults with rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriatic arthritis, and chronic plaque psoriasis.

New Safety Information

• Remicade is not authorized for pediatric use in Canada.
• Six (6) post-marketing cases of a rare type of lymphoma called hepatosplenic T-cell lymphoma (HSTCL) have been reported in pediatric and young adult patients taking Remicade for Crohn's disease.
• Exposure to Remicade® ranged from 1 or 2 infusions to over 4 years of maintenance therapy, and five of the six cases resulted in death.
• All cases reported concomitant or past use of other immunosuppressive agents, including azathioprine or 6-mercaptopurine. As a result, a causal relationship between Remicade and the development of HSTCL has not been clearly established.

The six reports of HSTCL in Crohn's disease patients documented ages ranging from 12 to 31 years, with five of the cases occurring in patients aged 12 to 19. Four of the six cases occurred in males. All reports originated from the United States, and one report was recently published in the literature.1

This disease is a very rare form of non-Hodgkin's lymphoma (NHL), which occurs most commonly in adolescent and young adult males, and there are only 150 cases published in the medical literature worldwide since the disease was first described in 1990.2 The disease usually presents as marked hepatosplenomegaly with bone marrow involvement and cytopenia, most commonly thrombocytopenia. Patients may have symptoms characteristic of B-cell lymphomas with fever, weight loss, and night sweats, but without lymphadenopathy or significant peripheral blood lymphocytosis. The clinical course of the disease is extremely aggressive, with a fatal outcome in most patients within 2 years of diagnosis.

Both azathioprine and 6-mercaptopurine are known mutagens, and azathioprine has been classified as a human carcinogen.3 There have also been three reports in the literature of HSTCL occurring in Crohn's disease patients receiving these drugs without Remicade. Because all cases described concomitant or past use of such agents, a causal association between Remicade® and HSTCL has not been clearly established. However, a role for Remicade in causing or exacerbating this disease cannot be excluded.

In Canada, approximately 38,000 patients have received Remicade since its launch in 2001, with 16,000 patients having received the product for Crohn's disease. Although lymphomas have been reported in Canada in patients receiving Remicade® for Crohn's disease and other indications, there have been no reports of HSTCL.

Information regarding the risk of lymphoma in patients receiving Remicade was also previously communicated to Canadian healthcare professionals in 2004.

Remicade is only authorized in Canada for the treatment of adult patients. The Canadian Product Monograph for Remicade® is being revised to include the above updated safety information.