Medical

Gene discovery explains why landmark drug fails in some Crohn’s disease patients

Gene discovery explains why la...
A single genetic variant may explain why anti-TNF drugs do not work in nearly 50 percent of Crohn's disease patients
A single genetic variant may explain why anti-TNF drugs do not work in nearly 50 percent of Crohn's disease patients
View 1 Image
A single genetic variant may explain why anti-TNF drugs do not work in nearly 50 percent of Crohn's disease patients
1/1
A single genetic variant may explain why anti-TNF drugs do not work in nearly 50 percent of Crohn's disease patients

New research from a large collaborative team of UK scientists has identified a specific genetic variant that may act as a biomarker for patients that are unlikely to respond to new biologic treatments. If confirmed in further trials the genetic biomarker could be used to easily personalize therapy in patients suffering from Crohn’s disease and ulcerative colitis.

Anti-tumor necrosis factor (TNF) drugs were introduced in the late 1990s and they undeniably revolutionized treatment for patients with severe Crohn’s disease and ulcerative colitis. The drugs work by disrupting the activity of TNF, a cell signaling protein involved in triggering inflammatory responses associated with a number of autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis.

For some patients these anti-TNF drugs were nothing short of miraculous, eliminating symptoms in a matter of weeks, but the treatment did not work consistently in everyone. Only 40 to 60 percent of patients showed effective disease remission, and the treatment lost its efficacy after a few years in some patients. Exactly why the new drug worked amazingly well for some and barely at all for others, was a mystery. The only thing scientists could be sure of was some patients seemed to develop immune antibodies that worked against the anti-TNF drugs.

In the largest genetic study of its kind, a team of UK researchers tracked over 1,200 patients with Crohn’s disease as they embarked upon anti-TNF treatment. The subjects were followed for one year, after which they were examined for rates of antibodies against the anti-TNF drugs. One particular genetic variant, dubbed HLA-DQA1*05, stood out in the patients who developed the most antibodies against the drug treatment.

The research seemed to indicate that those patients without this particular genetic variant displayed the greatest success from anti-TNF treatments. The study also notes that the cited genetic variant is not rare, with an estimated 40 percent of Europeans carrying the particular mutation.

“The future of Crohn’s and Colitis treatment is personalized medicine, so the identification of a genetic marker that explains why anti-TNF drugs don’t work for some people with Crohn’s is highly significant,” says Helen Terry, from Crohn’s and Colitis UK. “These results are extremely promising and with further research could lead to individualized treatment and better outcomes for the people living with these debilitating conditions.”

Anti-TNF treatments are not cheap, costing upwards of thousands of dollars per dose. Many major medical insurance plans around the word cover the treatment, albeit with varying conditions. Financially it is one of the most profitable new drugs in the 21st century. For example, just one anti-TNF iteration from corporate giant Johnson and Johnson, called Remicade, accounted for nearly 10 percent of that company’s entire global revenue in 2013.

The drugs are not without adverse effects either. From lymphoma in children to a risk of serious infection, major anti-TNF side effects can be rare but significant. So while rates of inflammatory bowel disease are rapidly increasing in Western populations it is important to better identify which patients these expensive new treatments will work for.

“We strongly believe that this type of research is essential to developing cost effective, treatment strategies for patients with inflammatory bowel disease,” says Tariq Ahmad, from the University of Exeter and corresponding author on the new study.

The new research was published in the journal Gastroenterology.

Source: University of Exeter

0 comments
There are no comments. Be the first!