MONTEREY, CALIF. — Development of new treatments for Crohn's disease or ulcerative colitis has generally focused on immunomodulators, cytokine therapy, and other biotechnology, but lower-technology options are now being tried as well, Dr. Joshua R. Korzenik said.
Probiotics, parasites, and fecal transplants each have shown some positive results, although none are ready for prime time, Dr. Korzenik said at an update in gastroenterology and hepatology sponsored by the University of California, Davis.
▸ Probiotics. Most studies on the use of beneficial bacteria to treat inflammatory bowel disease have not supported this strategy, but one study of treating pouchitis produced interesting and positive results. Researchers are studying probiotics in the treatment of Crohn's disease and ulcerative colitis, said Dr. Korzenik, codirector of the Crohn's and Colitis Center at Massachusetts General Hospital, Boston.
The pouchitis study included 40 patients who were treated for ulcerative colitis with colectomy and an ileoanal anastomosis (or J-pouch) operation and subsequently developed a chronic inflammatory process, a problem that occurs in about 15% of J-pouches. Antibiotics can control the pouchitis, but long-term antibiotics are not ideal.
After bringing the patients' pouchitis into remission with antibiotics, researchers discontinued antibiotic therapy and randomized 20 patients to a potent probiotic called VSL#3, with another 20 patients assigned to placebo. The pouchitis returned in all patients on placebo by 5 months later, but 17 patients in the probiotic group remained in remission 9 months after starting therapy (Gastroenterology 2000;119:305).
Typical probiotics found in health food stores contain perhaps 1–20 billion bacteria. VSL#3, which is sold over the Internet, contains about 1.6 trillion bacteria, and patients in the study took three capsules per day. “You're still talking about relatively small potatoes,” compared with the 100 billion to 1 trillion bacteria in each gram of stool, Dr. Korzenik noted.
The VSL#3 treatment regimen costs about $12-$15 per day and is not covered by insurance.
▸ Parasites. Some researchers speculate that when the modern zeal for cleanliness eliminated helminth ova (infectious parasite eggs) from humans, this actually aided development of Crohn's disease and ulcerative colitis, he said, so that adding the ova back to the body might treat these diseases.
In one open-label study, 29 patients with active Crohn's disease took 2,500 Trichuris suis (pig whipworm) ova every 3 weeks for 24 weeks (Gut 2005;54:87–90).
The disease responded to the treatment in 79% of patients, and 72% of patients achieved remission. “The results are almost too good to be true, but it's very promising,” Dr. Korzenik said. “It's not Fear Factor, so you're not taking down a cup of writhing worms. You're really just drinking down the eggs.”
A separate placebo-controlled trial in patients with ulcerative colitis showed marginal benefit.
The ova are sold from Europe over the Internet as an expensive product called TSO. “I suggested it be called Ova the Counter,” he joked. The Food and Drug Administration is considering whether sales should be regulated. “It's not cheap, but it's very exciting as far as something that's very nontoxic and may actually have some benefit,” he said.
▸ Fecal transplants. Also called “human probiotics” because the implanted bacteria come from donor stool, this treatment is modeled after fecal enemas used to treat some patients with refractory Clostridium difficile infection in order to reestablish normal flora.
In one open-label study of six patients with longstanding ulcerative colitis who received daily infusions for 1 week, all had improvement in symptoms (J. Clin. Gastroenterol. 2003;37:42–7). “At this point, I would not recommend this at all, but it's very curious,” Dr. Korzenik said.
Conventional therapy for inflammatory bowel disease is generally antibiotics or aminosalicylates for mild disease, corticosteroids for moderate disease, and infliximab or surgery for severe disease. Several new cytokine therapies are likely to be approved in the next few years. “The fear is we may go from too little treatment to overtreating these patients,” he said.