Abstract & Commentary
Synopsis: Administration of sterile viable Trichuris suis eggs to patients with active Crohn’s disease led to impressive clinical improvement.
Source: Sommers RW, et al. Gut. 2005;54:87-90.
Crohn’s disease is an often severely debilitating chronic illness that involves inflammation that can occur throughout the GI tract. It is now believed that this disorder results from inappropriate host immune responsiveness to normal gut flora. Helminths that infect the human intestine are known to reduce inflammation in several animal models of colitis, and they also demonstrably down-regulate host immune responses to unrelated antigens. In this study from Iowa, 29 patients with moderately active Crohn’s disease on various forms of conventional stable therapy received 2,500 live Trichuris suis ova every 3 weeks for 24 weeks. Viable eggs were derived from T. suis-infected pathogen-free pigs. Eggs were subsequently cultured in vitro and rendered virus and bacteria free. Patients had a mean age of 34, were 45% male, and had Crohn’s disease for a median of 3.9 years. Only 5/29 were not taking medication at baseline, and 10 of these had previously tried corticosteroids and immunosuppressive drugs. All patients were ill at enrollment with a Crohn’s Disease Activity Index (CDAI) of 296.7 ± 46.9 (moderate severity). No patients were lost to follow-up, and all were compliant. Twenty-two patients (75.9%) responded favorably by week 12 with a drop in CDAI of > 100 points. At week 24, 23 patients had responded (79.3%) and 21/29 were in remission. Results were not affected by age, sex, disease duration, smoking status (9/29 smoked), or disease location. There was a suggestion that patients receiving immunosuppression concurrently might have responded better (P = 0.017 for response at 24 weeks among this subgroup). Ileal resection may have lessened the likelihood of a favorable clinical response (P = 0.046). T. suis was very well-tolerated. Sommers and colleagues strongly recommend that larger controlled trials should be undertaken.
Comment by Malcolm Robinson MD, FACP, FACG
This trial was, of course, open label and of very limited size. Placebo response cannot be ruled out. Nevertheless, the reported clinical results are extremely impressive. As Sommers et al point out, Crohn’s disease is known to involve hyper reactive Th1 immune pathways. It has been suggested that the Th2 immune effects of infestation with helminths like T. suis may directly antagonize the immune pathways responsible for Crohn’s pathophysiology. In any case, various parasitic infections have been demonstrated to be capable of blocking experimental intestinal inflammation. It is certain that the administration of T. suis affects Crohn’s disease by mechanisms quite dissimilar to any of our current conventional therapeutic modalities. Crohn’s disease can be a terrible scourge, and we should be open-minded in our quest for safer and more efficacious therapy.