The advent of biological drugs has had a significant impact on the management of inflammatory bowel diseases. For an important group of patients with Crohn’s disease and ulcerative colitis, treatment with biologics has led to an improved quality of life, fewer admissions to the hospital and fewer side effects from corticosteroids and/or immunomodulators. Nonetheless, biologic agents are still being used with reluctance. The most frequently cited reasons for this are the high cost and uncertainty about long-term safety. The idea that biologic agents interfere with key molecules in the human physiology justifies these appropriate concerns. Indeed, many unexpected toxicity problems have occurred and been recognised as related to biologic therapies. A few examples include deterioration of heart failure and reactivation of mycobacterial infections with anti-tumour necrosis factor (TNF) agents,¹ the rare occurrence of lethal viral encephalitis with the anti-integrin antibody natalizumab,² and the dramatic cytokine release syndrome that was observed in healthy volunteers treated with a monoclonal antibody directed against CD28.³ Fortunately, stringent post-marketing surveillance programmes and registries have allowed early recognition of most of these problems and appropriate measures and guidelines have been developed to prevent and treat them. Given the facts that most biologic agents are immunogenic and could therefore lose their effect with time, that the ideal position of biologic agents in the management of Crohn’s disease and ulcerative colitis is still poorly defined, that most patients treated with biologics need induction and maintenance therapy and that the cost of these agents is likely to remain high, it is of paramount importance that the balance between efficacy and safety is carefully considered for every individual patient.

PROBLEMS IN TOXICITY ASSESSMENT OF BIOLOGIC THERAPY

Many patients who receive treatment with biologic agents have received other therapies or continue to use concomitant therapies to which the biologics are added (box 1). It is …