Safety of biologics – which lessons learned?

Abstract

The safety profile of biologics depends on the type of antibody, dose, mode of administration, concurrent medications and host factors. Opportunistic infections, including tuberculosis, remain an important safety concern. Development of an infection is one of the most common adverse events reported following the use of TNF-alpha inhibitors. For example, with an average follow-up of 51 weeks, 36% of all patients receiving infliximab in clinical trials developed an infection vs 25% of placebo-treated patients after an average follow-up of 37 weeks. In adalimumab trials for rheumatoid arthritis (RA), 1 infection per patient per year was identified in adalimumab-treated patients, compared with 0.9 infections per patient per year in placebo-treated patients. For both agents, most of these infections were easily treated upper respiratory or urinary tract infections. However, more serious infections, including pneumonia, sepsis, disseminated tuberculosis (TB), invasive fungal infections, and other opportunistic infections have been reported after anti-TNF-alpha agent use. Although the risk for serious infections in Crohn’s disease or RA patients may be due in part to their underlying chronic disease (with or without concomitant use of corticosteroids and immunosuppressive agents), evidence is accumulating that the use of biologic agents may further heighten that risk. All of the TNF inhibitors carry warnings in their prescribing information about the potential risk for serious infection. These agents should not be administered to patients with a clinically important active infection, and caution should be exercised when considering their use in patients with a chronic infection or a history of recurrent infection. For patients with Crohn’s disease, one should proceed cautiously in treating patients with perianal or intra-abdominal infections or patients with a phlegmonous process in the abdomen. For abscesses, drainage should