A drug called tofacitinib may help people with ulcerative colitis. As many as 700,000 Americans have this condition. It causes abdominal pain and diarrhea. About 1 in 5 people do not respond to current treatments. A study of the drug included 194 people. They were randomly assigned to get a dose of tofacitinib or a placebo. After 8 weeks, people taking tofacitinib had fewer symptoms. They also were more likely than people taking placebo to have their symptoms disappear. The drug works by reducing inflammation. The study was published in the August 15 issue of the New England Journal of Medicine. The Wall Street Journal wrote about it.

By Robert H. Shmerling, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

Imagine having a serious bout of diarrhea that just doesn't go away.

That's the reality for up to 700,000 people in the United States who have ulcerative colitis. It's a chronic condition of unknown cause marked by inflammation of the colon.

Symptoms include:

• Abdominal pain
• Diarrhea (often bloody)
• Fever
• Fatigue
• Weight loss

A number of treatments are available for ulcerative colitis. Fortunately, most people respond well to treatment. But up to 20% don't improve. They continue to have bothersome symptoms, despite trying one treatment after another. Even when a treatment works well, troublesome side effects are common. Surgery for ulcerative colitis may be helpful as a last resort, but better treatments could help people avoid surgery.

For these reasons, new and more effective treatments for ulcerative colitis can't come soon enough. That's why a new study of tofacitinib for people with ulcerative colitis is so important. Tofacitinib works differently than older treatments do. It’s a member of a new class of drugs called JAK inhibitors. These drugs reduce inflammation by blocking the signals that tell immune cells to become active.

In this latest research, nearly 200 people with poorly controlled ulcerative colitis were randomly assigned to receive a placebo or one of several doses of tofacitinib for 8 weeks. Compared to people taking placebos, those receiving higher doses of tofacitinib experienced:

• Fewer overall symptoms (as measured by a standard scoring system)
• More remissions (meaning that there are no symptoms or almost no symptoms)
• Side effects that were rare and generally minor

Researchers did notice an increase in blood levels of low density lipoprotein (LDL, or bad cholesterol) among those treated with tofacitinib. However, there also was an increase in high density lipoprotein (HDL, or good cholesterol). The importance of these changes is unclear.

These findings suggest that tofacitinib could be a safe and effective drug for people with ulcerative colitis. In fact, this study could lead to the drug’s approval in the near future. However, this study was small. Fewer than 50 people received each dose of tofacitinib. So we’ll need larger studies to fine out whether the risks of taking this drug are outweighed by its benefits.

What Changes Can I Make Now?

Ulcerative colitis is not considered preventable. However, you can take steps to limit symptoms and complications. These include:

• See your doctor for prolonged episodes of diarrhea. Early diagnosis and treatment can limit how long symptoms last.



• Take your medications as prescribed. While mild disease may require no treatment, a number of drugs are available to control symptoms:
  
  
  • Anti-inflammatory medicines related to aspirin, such as sulfasalazine (Azulfidine), mesalamine (Asacol, Pentasa, Rowasa) and olsalazine (Dipentum)
  
  
  
  • Immune suppressing medications, such as corticosteroids, azathioprine (Imuran), infliximab (Remicade) and cyclosporine (Neoral, Sandimmune)



• Get supportive care if you need it. Supportive care includes admission to the hospital for intravenous fluids, nutritional support and medicines to reduce bowel spasms.



• Change your diet. A healthy, well-balanced diet is recommended. If certain foods (such as dairy products) seem to worsen symptoms, they should be avoided.



• Get screened for colon cancer (with colonoscopy). This is particularly important because ulcerative colitis is a risk factor for colon cancer.



• Get screened for osteoporosis (with measures of bone mineral density). Poor nutrition and corticosteroids may weaken bones. Preventive treatment or treatment after osteoporosis develops can slow bone loss and even build stronger bones.

What Can I Expect Looking to the Future?

We need larger, more definitive studies of tofacitinib as a treatment for ulcerative colitis. However, if the results of this latest research are confirmed, tofacitinib may soon become a standard treatment.

You can also expect to hear more about the use of tofacitinib for other conditions. For example, it could prove useful for Crohn’s disease. This condition is closely related to ulcerative colitis. In addition, recent studies suggest that tofacitinib is effective for rheumatoid arthritis. And these could be just the beginning. Future research could prove that tofacitinib is effective for many conditions that cause chronic inflammation.