New Oral Treatments for Inflammatory Bowel Disease

 Biologics have been mainstay of treatment for moderate-to-severe IBD for the last two decades, gaining prominence and wide acceptance since the introduction of Remicade in the late 1990s. They have revolutionized IBD therapy and are still growing in numbers. There are three main groups : anti-TNFs ( Remicade, Humira, Simponi, Cimzia), anti-Integrins (Entyvio, Tysabri) and anti- IL 12/23 ( Stelara). They are all so-called monoclonal antibodies and need to be given as injection, some intravenously, some subcutaneously. They work, but not universally and all can provoke an immune reaction against themselves in the human body. They are also expensive and cumbersome to administer. I have been closely involved with their development as a clinical researcher.

The last few years brought oral medications for IBD to supplement, and maybe one day to supplant, the current biologics. First came Xeljanz ( Tofacitinib) and more recently Zeposia  (Ozanimod).

Xeljanz is a JAK inhibitor. This mechanism of action is similar to that of biologics: it disrupts one step of the cellular inflammatory response. It is rapidly effective in many patients. While it is generally safe, there have been serious side effects, such as the development of shingles and pulmonary embolism. Also, Xeljanz  is not active for Crohn’s Disease, although second generation JAK inhibitors show promise. Rinvoq, a selective JAK inhibitor, has just been approved for Ulcerative Colitis patients, who failed treatment with an anti-TNF agent.

Zeposia works differently. It captures the inflammatory cells before they can enter the tissue and traps them in lymph nodes. It seems safer and it shows promise for Crohn’s Disease, too. Other companies are working on newer versions of it.