Rheumatoid arthritis (RA) is a costly and debilitating autoimmune disorder that is characterized by joint pain, stiffness, and impaired functionality. Work at Imperial College identified tumour necrosis factor (TNF) as a key therapeutic target in the abnormal joint lining in RA. It established the concept of biological therapy demonstrating the use of an antibody to block a cytokine and treat chronic inflammatory disease. In 2012 Remicade® was the 4th best-selling worldwide drug with total global sales of $7.67 Billion.

Initial studies were dramatic

The identification of TNF as a key therapeutic target in the abnormal joint lining in RA began at Charing Cross Hospital and was published in 1993. The first clinical study performed enrolled 20 patients who were given a single infusion of infliximab, a monoclonal antibody to TNF. The results were dramatic and led to a large clinical trial in collaboration with three other European centres. Remarkably the response rate with the highest dose of infliximab was 79% at 4 weeks in comparison to 8% with placebo.

Repeated treatments were less effective

The success of repeated treatments was then investigated; however the degree of response was less, partly due to the monoclonal antibody inducing an immune response to itself which limited its effectiveness. Further studies indicated that combining an anti-TNF monoclonal antibody with a therapy targeting the T cells of the immune system might improve response through synergy and a reduction in immunogenicity. This finding led to combining methotrexate (MTX), already established in the treatment of RA, with infliximab in the next clinical trial. The demonstration of synergy with this combination of therapy, in the absence of increased toxicity, has set the gold standard of pharmacological management.

TNF blockade has changed the rheumatology practice. The introduction of infliximab has changed the way inflammatory bowel diseases and rheumatoid conditions are treated. More importantly, infliximab has offered significant improvement of the quality of life of many patients. In addition, infliximab has changed the natural course of these inflammatory diseases. The work at Imperial has had an ongoing impact across the globe for the treatment of inflammatory diseases. In 2012, Remicade was the 4th best-selling worldwide drug with total global sales of $7.67 Billion.

For further detailed information, please see the full impact case study at Threefold Increase in use of Anti-TNF in Chronic Inflammatory Conditions (PDF).