Postmarketing surveillance of anti-TNF drugs has shown hepatotoxicity to be another serious adverse event. Reports have ranged from death to the need for transplant because of cirrhosis. Most of the reports have been linked to infliximab.
The bottom line is that not only are anti-TNF agents less effective after a primary failure, but the rate of adverse events increases as well, judging from data reported at the annual meeting of the European League Against Rheumatism in 2008 by Dr. Luba Nalysnyk of United BioSource Corp. Dr. Nalysnyk and associates performed a meta-analysis of 16 articles and 15 abstracts involving 5,306 patients. In the meta-analysis, primary failure of an anti-TNF agent occurred in 48% of patients. A second anti-TNF agent did not work in 66% of those patients, and another 66% of those patients developed adverse events in response to the second agent.
Not all physicians are comfortable switching patients after one failure to a drug that works by a mechanism other than blocking TNF. But for those who are, they must decide how to choose between abatacept, rituximab, and tocilizumab, Dr. Furst said. All three agents pose the same risk of bacterial infection. Rituximab may be the drug of choice in patients with a history of lymphoma or solid tumor. The risk for infusion reaction is less with abatacept than with rituximab or tocilizumab. The data on tocilizumab look good so far. In patients with chronic or latent TB, either abatacept or rituximab may be a better choice than is tocilizumab.
SDEF and this news organization are owned by Elsevier. Dr. Furst has disclosed financial relationships with Abbott, Actelion, Amgen, Array, Biogen Idec, BMS, Celgene, Centocor, Genentech, Gilead, GSK, the National Institutes of Health, Nitec Pharma, Novartis, Roche, UCB, and Wyeth.