New, broad-spectrum UC treatments available, in pipeline

It’s an “interesting time” in treatment options and advances in ulcerative colitis, according to William J. Sandborn, MD, chief of the Division of Gastroenterology at the University of California, San Diego.

A broad range of treatment options have become available and more are in the phase 3 pipeline. Sandborn said the days when steroids were the only treatment options for UC are over.

“It’s never a good time to have UC, but compared to years past, there are some new treatment options and a lot more in the pipeline that give patients options they didn’t have before.”

WILLIAM J SANDBORN, MD

William J. Sandborn

In the past, steroids had been the first line of treatment for UC. More recently, tumor necrosis factor-alpha antagonist treatments are available.

“We’ve had three anti-TNF drugs approved over the last 9 years. That’s a big advancement for the treatment of UC.”

New mechanisms for treatment

The most recent drug approved to treat UC and Crohn’s disease is a new type of drug, vedolizumab (Entyvio, Takeda Pharmaceuticals).

“It blocks the alpha-4 beta-7 integrin receptor and blocks lymphocyte trafficking into the gut, so it’s a new mechanism of action,” Sandborn said in an interview with Healio.com/Gastroenterology. “The data so far indicate it doesn’t have significant systemic immunosuppressant properties, so that differentiates it from older drugs, like steroids and immunosuppressants. So, having a new mechanism of action that targets the gut is particularly interesting to physicians and patients,” he said, and added that many patients in clinical trials experienced and maintained remission and showed improvement or complete healing of the bowel at endoscopy.

He said about 50% of patients in the trials responded to vedolizumab in about 6 weeks, and roughly half of those patients continued to respond over the course of a year. The clinical trials were particularly impressive, according to Sandborn, because about half of the participants had failed other treatments, including alpha-TNF antagonists.

“We certainly have an unmet need for what to do with patients who have failed TNF inhibitors. This gut selectivity makes it interesting for some patients, even as a first-line biologic,” he said.

Another advancement in UC treatment is the availability of therapeutic drug monitoring tests for the TNF antagonists infliximab and adalimumab, Sandborn said.

Broad array of treatment options

Mesalamine drugs are also still used to treat patients with UC, but like other treatments, not all patients respond, so the availability of other treatment options is important.

In clinical trials, Sandborn said Janus kinase, or JAK, inhibitors are showing promise. He said the drug that is furthest along in phase 3 is tofacitinib (Xeljanz, PF Prism CV), an immunosuppressant, and he has been involved with its research.

Other approaches are being studied, as well. Sandborn said that food maker Nestle has backed Chinese drug maker Hutchison Medipharma (Chi-Med) in a partnership called Nutrition Science Partners. The group is involved in a phase 3 study the concentrated Chinese herb, andrographis paniculata, to treat UC. In phase 2 studies, many patients with mild to moderate UC responded well to treatment, he said.

Treatment monitoring available

“There are clinically available assays for [testing blood levels of infliximab and adalimumabs] to fine-tune the dosing and treatment of patients with UC, and Crohn’s disease as well. That’s something new — personalized medicine and giving personalized dosing to make sure individual patients have enough of the drug.”

Causal factors still unknown

According to Sandborn, dietary components have been studied in UC patients, and no clear statistical association has been made regarding the elimination of certain foods from a patient’s diet.

“We’ve not yet identified a food allergen that accounts for a substantial fraction of patients.” Clinical trials have been conducted in which patients received no oral food and were solely provided IV nutrition, and UC outcomes did not appear to be altered, he said.

“On one hand, that’s kind of discouraging, but on the other hand, we can see with Westernization, in the last 30 years, UC and then CD came to Japan, and then South Korea about 20 years ago, and it’s now come to China and India.”

He said in the past, many physicians who were trained in the US were trained extensively in UC and CD, and on returning to their home country, did not encounter the disease until more recently. “With modernization comes IBD,” he said, though it is unclear which factors pose the greatest risks.   

Surprisingly, Sandborn said smokers are half as likely to develop IBD, but it is unknown why smoking cigarettes offers a protective factor. His prior research with nicotine patches demonstrated only a modest effect, and he speculates something else in cigarette smoke, possibly CO, is behind the effect.

“Obviously, smoking has many harms, so we don’t recommend it for UC, but that’s the strongest epidemiological link that we know of,” he said. -- By Shirley Pulawski

Disclosure: Sandborn has served as a consultant to Janssen, AbbVie, Takeda, Pfizer, and Nutrition Science Partners.

See more from Ulcerative Colitis Resource Center