Recent advances in our understanding of how both Crohn’s disease and ulcerative colitis develop, have led to research that explores new avenues for treating inflammatory bowel disease (IBD). While none of the therapies mentioned represent a “cure” for IBD, here are a few therapies that you should know about.
Anti-TNF agents have been used to treat immune mediated conditions, including IBD for more than 20 years. They work by suppressing the activity of tumor necrosis factor (TNF), a key element in your body’s inflammatory pathways. Anti-TNF agents have known side effects, such as infections, that must be carefully monitored. Despite the side effects, these agents will continue to be an integral part of IBD management in the coming years.
Vedolizumab is a new gut-specific monoclonal antibody that has shown promising results in treating both Crohn’s disease and ulcerative colitis. Vedolizumab works to block the movement of white blood cells into the GI tract, which helps to control inflammation and symptoms of ulcerative colitis and Crohn's disease. The localized, targeted nature of vedolizumab has the potential advantage of effectively treating IBD, without impacting the rest of the body’s immune system which may lead to lower chances of infections outside the bowel such as pneumonia.
Vedolizumab has been approved in Canada for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response, loss of response to, or were intolerant to either conventional therapy or anti-TNF agents. In the United States it has been approved for use in adults with moderate to severe Crohn's and colitis who have failed to respond or inadequately responded to one or more of the standard therapies such as steroids, immunomodulators, or anti-TNF agents. Vedolizumab is administered intravenously. Other medications (Etrolizumab, AJM300, AMG181, PF-00547659) that work similarly to vedolizumab are currently in clinical trials.
Promising therapies in progress
Ustekinumab is a monoclonal antibody that has been approved to treat autoimmune conditions such as plaque psoriasis and psoriatic arthritis. It targets signaling molecules called cytokines (IL-12 and IL-23) that cause ongoing inflammation in Crohn’s disease. In one study, compared to placebo, ustekinumab led to significantly higher proportions of clinical remission (41.7 vs. 27.4%) and response (69.4 vs. 42.5%) in patients who were previously resistant to anti-TNF therapy. Ustekinumab is currently in its last phase of clinical study for the treatment of Crohn's disease.
Tofacitinib is an oral drug that works by blocking certain molecule (called janus kinase) that contribute to inflammation. It has been approved for treatment of rheumatoid arthritis and is currently being studied for treatment of IBD and other autoimmune conditions. In a clinical study, tofacitinib has demonstrated significantly better clinical remission after 8 weeks when compared to placebo. However, it did unfavorably increase levels of low-density lipoprotein cholesterol. Nonetheless, it shows promise as a future treatment for ulcerative colitis.
Therapies in their early stages of development
Stem cell therapies include hematopoietic stem cell transplantation and mesenchymal cell infusions. These therapies have been reserved for the most challenging forms of Crohn’s disease. Hematopoietic cells and mesenchymal cells have the ability to differentiate into a variety of cells. Stem cell therapies act by potentially resetting the body’s immune system. However, very limited studies have been carried out using these treatments. Though these therapies show promising results, there is also the potential for significant side effects such as continued use of immunosuppressive drugs and higher incidence of infections. Further studies are required to fully evaluate the benefits and risks of stem cell therapies in treatment of Crohn’s disease.
Chemokines and chemokine receptor antagonists block recruitment and migration of white blood cells into the gut mucosa thereby reducing the potential for inflammation. In several studies, they have been shown to increase clinical remission in IBD patients and response when compared to placebo. However, more studies will be needed to measure their effectiveness in the treatment of IBD.
HMPL-004 (Andrographis paniculata extract) has been shown in animal studies to exhibit potent anti-inflammatory properties. It has been shown to provide significantly better clinical response in patients with mild-to-moderate ulcerative colitis when compared to placebo. Further studies assessing its role in the treatment of severe ulcerative colitis are necessary.
It is hopeful that some of these therapies will eventually obtain FDA, NICE and Health Canada approval for treatment of IBD. As scientists further decipher the underlying causes of IBD, new therapies will emerge and ongoing research is certain to improve the management of IBD.