Three anti-tumour necrosis factor alpha (anti-TNFα) agents are registered in Singapore – etanercept (Enbrel®, Wyeth), adalimumab (Humira®, Abbott) and infliximab (Remicade®, Centocor). These products are indicated for the treatment of rheumatoid arthritis with Remicade® having additional indications for Crohn's disease and ankylosing spondylitis.
Anti-TNFα agents exert their actions by binding to human TNF, which are proinflammatory and immunoregulatory cytokines. When TNF are overexpressed, they mediate chronic inflammation.
Post-marketing reports
Rare cases of hepatitis B virus (HBV) reactivation have been reported in patients receiving anti-TNFα therapy. From 2003 to date, there are at least seven published cases of HBV reactivation associated with the use of these products.1-6 These seven patients were positive for HBV surface antigen prior to anti-TNFα treatment and the clinically active HBV infection occurred following a latency period ranging from 1 – 18 months after initiation of anti-TNFα therapy (mainly with infliximab). With the exception of one fatal case, the HBV conditions were controlled with discontinuation of anti-TNFα treatment followed by administration of lamivudine.
Regulatory actions
In Jan 2006, Health Canada issued a public advisory 7 on the safety profile of these three products which include the following information:
- HBV reactivation has been reported very rarely in patients with chronic hepatitis B infection receiving the anti-TNFα agents: Enbrel®, Humira® and Remicade®.
- Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating anti-TNFα therapy. Those identified as chronic HBV carriers (i.e. surface antigen positive) should be monitored for signs and symptoms of active HBV infection throughout the course of therapy and for several months following discontinuation of therapy.
- Reactivation of HBV is not unique to anti-TNFα agents and has been reported with other immunosuppressive drugs.
Local situation
HSA has not received any local report pertaining to HBV reactivation associated with the use of these products. However, we are working with the pharmaceutical companies to strengthen the local package inserts to include this new safety concern.
References
- World J Gastroenterol 2006; 12:974-6.
- Dig Dis Sci 2005; 50:163-6.
- Ann Rheum Dis 2005; 64:788-9.
- Gut 2004; 53:1363-5.
- J Rheumatol 2003; 30:1624-5.
- Ann Rheum Dis 2003; 62: 686-7.
- Health Canada. Advisories Warnings and Recalls for Healthcare Professionals. Jan 2006.
