Infliximab (Remicade®), was registered in Singapore in November 2002 and is licensed for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). Infliximab is a chimeric human-murine monoclonal antibody that binds to human tumour necrosis factor alpha (TNFα). TNFα is a pro-inflammatory and immunoregulatory cytokine that, when over expressed, mediates chronic inflammation in diseases such as Crohn's disease and rheumatoid arthritis.
HSA would like to inform healthcare professionals of important safety information concerning Remicade®.
A) Malignancies
The US FDA's Arthritis Advisory Committee reviewed the safety data for marketed TNF blockers including Remicade® in March 2003. Safety data from controlled clinical trials and post-marketing experience were examined.
i) Lymphoproliferative disease (LPD)
In the committee's report to FDA in 2003, a total of 71 cases of LPD associated with Remicade® was recorded from spontaneous reports, clinical trials and disease registries. The majority of cases (n = 48) were classified as malignant lymphoma. Among 2,410 patients treated with Remicade® in clinical trials with a median of 1.1 yrs of follow-up, 3 patients developed lymphomas. This is approximately 3-fold higher in RA clinical trial population and 6-fold higher in the overall clinical trial population than expected in age-, gender-, and race-matched general population based on the US Surveillance, Epidemiology and End Results Database. No further information is available to date.
Combined, available studies in medical literature indicate that the baseline risk of LPD in patients with RA and CD, particularly patients with highly active disease and/or chronic exposure to immunosuppressants, is higher than the general population. The potential role of TNFα and the development of malignancies are not known.
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ii) Non-lymphoproliferative malignancies
There were 354 non-LPD malignancies reported in the post-marketing database for Remicade® from August 1998 to August 2002. The most frequently reported malignancies were skin cancer (n = 77), gastrointestinal cancers (n = 68), breast cancer (n = 58) and respiratory cancers (n = 53). There is insufficient data to determine whether Remicade® contributed to the development of these malignancies. The observed rates and incidences were reported to be similar to those expected for the population studied.
B) Haematological events
Cases of leukopenia, neutropenia, thrombocytopenia and pancytopenia, some with fatal outcome, have been reported in patients receiving Remicade®. The causal relationship to Remicade® therapy is unclear. Although no high-risk group(s) has been identified, caution should be exercised in patients being treated with Remicade® who have ongoing or a history of significant haematological abnormalities. Doctors should advise patients to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g. persistent fever) while on Remicade®. Discontinuation of Remicade® therapy should be considered in patients who develop significant haematological abnormalities.
References
Information for the Arthritis Advisory Committee Briefing Document, 4 March 2003, Remicade® (infliximab), Efficacy and Safety Review.
