September 5, 2008


Due to heightened concerns over a side effect that can leave users prone to infection, the FDA has flexed its new powers to impose safety warnings on anti-TNF drugs. However, Datamonitor believes that while this action may raise awareness of the side effect, it will not affect drug uptake in the many patients with autoimmune diseases that find relief in these therapies.

The FDA has exercised its new authority, under the Food and Drug Administration Amendments Act (FDAA) of 2007, to demand safety-related changes to the labeling of anti-TNF (tumor necrosis factor) drugs. The manufacturers of Humira, Cimzia, Enbrel, and Remicade must strengthen the existing warnings on the risk of developing opportunistic fungal infections, after the FDA reviewed 240 cases of histoplasmosis in patients using these drugs.

Histoplasmosis is very rare in healthy adults, but is more commonly seen in immuno-compromised patients, so much so that its presence is a diagnosing factor for HIV patients. TNF inhibitors act on the immune system, and infections in general are a known side effect.

Currently, Humira, Remicade and the recently launched Cimzia mention 'invasive fungal infections' in black box warnings within their prescribing information. The Enbrel labeling does not specify fungal infections within the black box area, but includes an additional paragraph within the text of the document referring to the observation of post-marketing fungal infections. However, none of the brands specify histoplasmosis. Under the new regulations, all companies involved have 30 days to change the labeling or provide a reason why they do not believe changes are necessary; however, the final ruling on this lies with the FDA.

As these warnings already exist in most of these drugs' prescribing information, Datamonitor believes the rationale behind the FDA's implementation of its new found powers is to highlight the need for physicians to recognize these infections. Almost 9% of the 240 reported histoplasmosis cases were initially undiagnosed and over half of those patients died of their infections. Histoplasmosis can be asymptomatic or initially resemble influenza, so there is definitely a need for greater awareness.

Despite the high profile of this action in the healthcare media, the warnings are unlikely to have much impact on prescribing behavior. Sales in this class amounted to almost $6 billion across the seven major markets in 2007, and with a combined sales forecast of nearly $10 billion in the next five years, Datamonitor does not expect them to be adversely impacted. This news, however, will hopefully increase physician and patient vigilance.