Pig Whipworm Ova Found Active in Crohn's Disease and Ulcerative Colitis

May 19, 2004

May 19, 2004 (New Orleans) — Orally ingested ova of Trichuris suis, the porcine whipworm, has been found to be active in an open-label study of Crohn's disease, and in a small scale, placebo-controlled trial in patients with ulcerative colitis.

"Inflammatory bowel diseases are diseases of the 20th century," said Joel V. Weinstock, MD, from the University of Iowa Carver College of Medicine in Iowa City, in a press briefing here during Digestive Disease Week. "These diseases are extremely rare in less developed countries, suggesting that we're doing something different."

These trials were designed to explore the hypothesis that infection with parasitic worms (helminths) is protective or ameliorating in these conditions, because such infections down-regulate immune responses.

In the open-label trial, 29 patients with refractory disease, and a Crohn's disease activity index (CDAI) of 220 to 450, ingested 2,500 T. suis ova in a beverage every three weeks for 24 weeks. By week 12, 22 patients (75.9%) experienced a decrease in CDAI of more than 100 points, or had a CDAI of less than 150. Another 18 patients (62.1%) were in remission. (Four patients withdrew early because of disease activity or pregnancy.) Researchers and patients observed no adverse effects or complications.

In the controlled trial, 54 patients with an ulcerative colitis disease activity index (UCDAI) of 4 or higher (mean UCDAI at baseline was 8.7, with a standard deviation [SD] of 2.2) were randomized to drink 2,500 ova or placebo every two weeks for 12 weeks. (Both beverages contained charcoal to mask the presence of the ova.) At 12 weeks, patients who had not yet experienced disease remission crossed over to the other group of the study for another 12 weeks. Blinding was maintained throughout.

At the end of the first 12 weeks, 13 (43.3%) of the 30 patients who ingested ova experienced meaningful disease improvement, compared with four (16.7%) of 24 patients receiving placebo (P = .04). The mean UCDAI in this group decreased to 2.8 (SD ± 1.4), with a mean improvement in score of 6.0 points (SD ± 2.2). After the second 12 weeks, 56.3% of patients with active disease responded vs. 13.3% of those receiving placebo (P = .02). When they combined the results from the two 12-week periods, the researchers found a statistically significant 47.8% overall response rate to the ova compared with a 15.4% response rate to placebo (P = .002).

Helminths are parasitic animals that live in the gastrointestinal tract or bloodstream. "In less developed countries, 100% of children have worms in their gastrointestinal tract," Dr. Weinstock said. Helminths' effects on the immune system are long-lasting, with changes detectable a decade after the worms have been removed, he added. "You can argue that it's our [industrialized] immune systems that are deviant," he said.

Dr. Weinstock noted that they could not study the human whipworm, T. trichiura, for ethical reasons, so they administered the porcine equivalent. When subjects swallow the pig whipworm ova, the helminths colonize the gut for only a short time, because they have not evolved to live parasitically in humans.

"It's a fascinating idea, and there is basic science to support the idea that it should work," said James D. Lewis, MD, from the Inflammatory Bowel Disease Program at the University of Pennsylvania in Philadelphia, in an interview. "But lots of things look promising and don't work in the end." He added that even if the treatment proves effective and safe in larger patient populations, matters of federal regulation, production, and distribution could be unusually difficult for such a novel biologic.

This work was funded by the Broad Foundation, the National Institutes of Health, the Crohn's and Colitis Foundation of America, and general laboratory funding. The authors report no pertinent financial disclosures.

DDW 2004: Abstract 580, presented May 18, 2004; abstract 644, presented May 18, 2004.

Reviewed by Gary D. Vogin, MD



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