Therapeutic Options in Ulcerative Colitis: Choosing Initial Therapy Is Key

In an era of emerging therapies for the treatment of ulcerative colitis (UC), choosing therapies for patients should be done thoughtfully, according to a presentation by David T. Rubin, MD, at the Advances in Inflammatory Bowel Diseases (AIBD) Regional in Chicago, Illinois.

“The first therapy will work best,” said David T. Rubin, MD, professor of medicine and section chief of Gastroenterology, Hepatology, and Nutrition at the University of Chicago.

There are numerous treatments available for the treatment of UC including 5-aminosalicylates (5-ASA; sulfasalazine and mesalamine); corticosteroids (prednisone and budesonide); immunomodulators (azathioprine/6MP, cyclosporine, and tacrolimus); biologics (infliximab, adalimumab, certolizumab pegol, golimumab, and vedolizumab); and small molecules (tofacitinib).

“For many years, 5-ASA has been the primary approach for mild to moderate ulcerative colitis,” Rubin said.

Despite its frequent use over time, large gaps in care remain with 5-ASA therapies.

“There are a large group of patients who do not achieve remission, so there is clearly a need for better therapies.”

For moderate to severe UC, biologic therapies and tumor necrosis factor (TNF) inhibitors are available treatment options. There are 3 anti-TNF inhibitors—infliximab, adalimumab, and golimumab—approved by the FDA for use. However, serious infections and opportunistic infections can occur, so a need for other treatment options remains.

Anti-integrin therapy, such as the biologic vedolizumab, is an important option for the treatment of UC and Crohn disease (CD). Rubin highlighted the long-term safety data from the GEMINI study of 1966 individuals who received treatment with vedolizumab. Results indicated no new concerns with continuous vedolizumab treatment.

“[Anti-integrin therapy] blocks white blood cells on the way to the intestines,” said Rubin. “This is a different mechanism and an important consideration [for therapy].”

Tofacitinib is the only small molecule therapy available for the treatment of moderate to severe UC. The optimal regimen of tofacitinib is 10 mg twice daily for 8 weeks, with the possibility of extending for 8 more weeks. This should be followed by 5-10 mg twice daily depending on the patient’s therapeutic response, according to Rubin.

“Tofacitinib works rapidly and well,” Rubin said. “[However], it is a potent immunosuppressant with quick onset, so we have to keep safety in mind.”

Herpes zoster (HZ) can also occur while a patient is receiving treatment with tofacitinib. However, it is not unique to tofacitinib, according to Rubin. In fact, HZ rates with tofacitinib have become stable over time.

“Herpes zoster occurs with anti-TNF therapy as well and when patients are older and on immunosuppressants,” Rubin said. “We should consider the herpes zoster vaccine as a standard vaccine for these patients.”

Dr Rubin noted that studies have shown TNF-naive individuals do better with tofacitinib and vedolizumab than those who already failed biologic therapy. “This may be as simple as the sicker patients are more resistant to medications than others, but it raises the question of which medications should patients be treated with first,” said Rubin.

Specific scenarios that should be considered when choosing treatment among individuals with moderate to severe disease were mentioned during Dr Rubin’s presentation:

• Vedolizumab for individuals with IBD aged 60 years or older.
• Anti-TNF or tofacitinib for individuals with UC with synovitis arthritis.
• Cyclosporine, tacrolimus, or tofacitinib for individuals with UC with low albumin.

Other therapeutic options in development include more anti-integrin therapies, anti-interleukin, janus kinase inhibitors and TYK2, S1P receptor modulators, and microbial therapies.

Fecal microbiota transplant may also serve as a potential future treatment option for patients. “There are multiple randomized-controlled studies that show some benefit, but the treatment is not uniform, there is unclear donor selection, and FDA regulatory issues to consider,” Rubin said.

—Melinda Stevens

Reference:

Rubin DT. Recent and emerging therapies for UC. Presented at: Advances in Inflammatory Bowel Disease Regionals. July 20, 2019; Chicago, IL.