Autoimmune Answers

While diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), have been described in the medical literature for over two hundred years, the recognition of their autoimmune pathogenesis became apparent only around the middle of the 20th century. The concept that the human immune system could break tolerance and generate an immune response was a source of great controversy at that time because of the philosophical and religious implications that this concept carried. Even the great pharmacologist, Paul Ehrlich, postulated that: “It would be dysteleologic in the highest degree, if under these circumstances selfpoisons of the parenchyma – autotoxins – were formed”. However, through the work of Donath and Landsteiner, and more recently the likes of Doniach & Roitt, it is now accepted that in certain individuals tolerance to self antigens could be broken and that this contributes to autoimmune disease (1,2).

Current estimates suggest that there are over 80 described autoimmune diseases thought to account collectively for one third of all premature deaths and disability in the Western world. In 2005, the National Institutes of Health estimated that two to eight per cent of the US population had some form of autoimmune disease. The estimated incidence of autoimmune diseases range from less than one or two per 100,000 person-year (such as scleroderma) to more than 20 per 100,000 person-year (such as adult onset RA) with the prevalence ranging from less than five per 100,000 (such as uveitis) to more than 500 per 100,000 (such as RA). While there is a great deal of heterogeneity between different autoimmune diseases, all involve aberrant inflammation to selfantigens that often result in tissue damage, causing a high degree of morbidity and, in some cases, death. Consequently, it has been estimated that drug sales for autoimmune diseases in 2007 were in excess of $20 billion, with a prediction that this will reach $50 billion by 2015, with the majority of the growth being driven by antibodies (see Table 1).

MONOCLONAL ANTIBODY THERAPIES

Prior to the use of monoclonal antibodies (Mabs), a large number of small molecules, ranging from anti-inflammatories and analgesics to antimalarials and glucocorticoids, were used in an attempt to slow disease progression. However, these drugs provide symptom control at best and are often associated with significant side effects. As such, there is a clear need for targeted therapies that modify the autoimmune disease process with an acceptable safety profile.