A new therapy that combines two existing drugs shows promise for patients with inflammatory bowel disease who have exhausted other treatment options, according to findings from two new trials.
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“These studies are really quite significant,” said Dr. Uma Mahadevan, a gastroenterologist and an expert on inflammatory bowel disease at the University of California, San Francisco.
The two randomized controlled trials provide, for the first time, hard data to support combination drug therapy to fight inflammatory bowel disease, said Mahadevan, who has no connection to the studies.
Results from the trials are being presented Tuesday at “Digestive Disease Week,” an annual medical conference taking place in Chicago.
Up to 3.1 million people in the United States have the lifelong disease, which occurs when the body’s immune system attacks healthy cells in the intestines, or bowel.
Symptoms include diarrhea, stomach pain, fatigue, nausea and untended weight loss.
Both so-called phase 2b trials enrolled patients with moderate-to-severe disease who had already failed one or more therapeutic classes of drugs. Phase 2b trials are designed to confirm a drug’s efficacy and determine its optimal dose and are not the final word. The next step would be larger, Phase 3 trials.
One trial analyzed 693 patients with Crohn’s disease, while the other analyzed 572 patients with ulcerative colitis, the two main types of inflammatory bowel disease. Their symptoms are similar, however they attack different parts of the digestive track in different ways.
The trials tested an experimental therapy that combined golimumab and guselkumab, which are already in the market. Each drug is either injected or infused through an IV line and, taken alone, they target different proteins that drive inflammation.
“The concept is to achieve better efficacy by combining two different mechanisms of action,” said Bruce Sands, a gastroenterologist at Mount Sinai Health System in New York and the lead author of the Crohn’s disease study. Sands is a paid consultant to Johnson & Johnson, the maker of the experimental therapy and the trials’ sponsor.
It seemed to work, particularly for patients who had previously failed two or more advanced classes of therapies, such as biologics. Biologics, including golimumab and guselkumab, are derived from living organisms and can be used to treat auto-immune diseases.
In the Crohn’s trial, 49.2% of the most treatment-resistant patients who received a high dose of the combination therapy achieved clinical remission after 48 weeks, compared to 27.3% receiving guselkumab and 23.1% taking golimumab.
In addition, the patients in this group taking the experimental therapy had fewer ulcers and less inflammation in their intestines than those taking the single drugs. And the safety profile was about the same.
The results of the ulcerative colitis trial showed a similar pattern.
An estimated 10 to 20% of patients with inflammatory bowel disease eventually have two or more advanced drug therapies fail them, said Dr. Victor Chedid, a specialist in the disease at the Mayo Clinic in Rochester, Minnesota. These two trials “focused on that small but critical group of patients,” said Chedid, who was not involved in the studies.
Chedid called the results “exciting” but cautioned that Phase 3 trials are needed to confirm them. Sands said those trials are expected to start recruiting patients later this year.
For patients who have tried multiple drugs without success, surgery to remove the inflamed tissue and to repair the damage is the last option. For ulcerative colitis, surgery to remove the colon, or large intestine, usually achieves remission, said Mahadevan. On the other hand, Crohn’s disease can attack any part of the digestive tract, so surgeons typically remove only the affected area. But it often returns.
Tess Koman, 34, has had 20 abdominal surgeries for Crohn’s disease. She was diagnosed when she was age 7 and has only about half of her bowel remaining.
“It’s all stuck together, and it’s just a mess in there, and that is a result of both Crohn’s and the good faith attempt over the years to treat it,” said Koman, who is a food writer and editor. Even when drugs have helped, she still needed surgeries. “I have such a varied track record with different classes of drugs either being OK for a bit or not OK at all.” For example, she has had allergic reactions to biologics.
Dr. Maria Abreu, a gastroenterologist and the lead author of the ulcerative colitis study, believes that after doctors learn of the findings, “I expect they’ll have a light bulb moment and, for those patients who are not doing well, consider combination therapies.”
However, with the experimental combination drug still in the research stage, they would have to prescribe golimumab and guselkumab individually. The same would apply to any combination of existing drugs prescribed for inflammatory bowel disease.
Doctors who see more complex cases are already trying to use more than one class of medication at a time, but convincing insurance companies to approve two different prescriptions is difficult, Chedid said.
“Sometimes you have to do multiple appeals with insurance companies to make the case that your suffering patient who has more severe disease needs dual therapy so that you can salvage their colon or small intestine,” said Chedid. “It’s something that we try to do in practice in very, very select cases.”