A new study from researchers in Denmark may lead to a method of determining how patients with inflammatory bowel diseases will react to a certain drug, before the treatment is administered. The research, published in Alimentary Pharmacology and Therapeutics, showed that there may be a way to test for a person's susceptibility to an allergic reaction to the drug infliximab, which is used to treat diseases like Crohn's or ulcerative colitis.
According to the DrugBank database, infliximab is a chimeric antibody, meaning it contains both human and house antibodies. It binds to a group of molecules called tumor necrosis factors, specifically TNF-alpha, and inhibits the binding of these molecules to their receptors. This reduces the production of other pro-inflammatory molecules, making the drug effective in treating inflammatory diseases like Crohn's, or even rheumatoid arthritis.
But infliximab does have side effects, including severe allergic reactions, according to publisher Wiley. The allergic reactions can be fatal for some. For other patients, the drug, which can cost up to $20,000 a year, can stop working altogether.
For this new study, which was also presented at the European Crohn's and Colitis Organisation's annual meeting this past February, the team used data it had collected that suggested the presence of a biomarker in the blood that could determine whether a patient would respond to infliximab or have an allergic reaction to it before it was administered.
The researchers conducted an observational, retrospective study of 29 Crohn's patients and 22 ulcerative colitis patients. They analyzed blood samples taken from the patients, before they began infliximab treatment, to look for anti-infliximab antibodies that could indicate whether treatment would fail. They found that Crohn's patients who went into remission after a year's treatment with infliximab had lower levels of these anti-infliximab antibodies before treatment began than patients who either never responded to the treatment at all or who stopped responding after a short period of time. The team also observed a similar trend in the ulcerative colitis patients.
They also found that patients who developed allergic reactions to the treatment tended to have markedly high levels of these anti-infliximab antibodies pre-treatment than patients who didn't develop an allergic reaction.
"[Infliximab]-Fab reactive IgG antibodies present in serum from [inflammatory bowel disease] patients before infliximab therapy associate with lack of long-term efficacy and safety," the team wrote. "Assessments of such antibodies may help clinicians to choose between treatment with infliximab and more humanized agents" that don't contain the mouse-derived antibodies.
Source: Steenholdt C, Palarasah Y, Bendtzen K, et al. Pre-Existing IgG Antibodies Cross-Reacting with the Fab Region of Infliximab Predict Efficacy and Safety of Infliximab Therapy in Inflammatory Bowel Disease. Alimentary Pharmacology and Therapeutics. 2013. 2013.