Researchers in a new study analyzed the outcomes of a clinical trial comparing standard therapy with hematopoietic (blood) stem cell transplantation (HSCT) in Crohn’s disease patients and found that HSCT did not result in a statistically significant improvement over conventional therapy. The study, titled “Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial,” was published in The Journal of the American Medical Association (JAMA).
Crohn’s disease (CD), an inflammatory bowel disease (IBD), is an autoimmune disorder characterized by an exacerbated inflammation that can affect any part of the gastrointestinal (GI) tract. There are several treatment options for CD, including medication, diet and nutrition modifications, and surgery to repair or remove affected parts of the GI tract. Standard care usually involves immunosuppressive drugs designed to halt the immune system’s abnormal inflammatory response. However, select patients do not respond or develop resistance to this treatment.
Previous studies have suggested that hematopoietic stem cell transplantation may be a beneficial therapy for some CD patients. To test this premise, researchers conducted a clinical trial to assess the effect of HSCT on relapsing CD. The Phase 3 study (NCT00297193), conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013, enrolled 45 patients (ages 18 to 50) with refractory CD and not amenable to surgery, despite treatment with several immunosuppressive agents and corticosteroids. All patients underwent stem cell mobilization and were randomized to immunoablation and HSCT (23 patients) or to control treatment, where 22 patients had the HSCT deferred for a year.
Results showed no statistical significance in sustained disease remission, achieved in two patients in the HSCT group and one patient in the control group after one year of treatment. Discontinuation of therapy in the last three months was observed in 14 patients who underwent HSCT and in five control patients, which was statistically significant. Remission [Crohn Disease Activity Index (CDAI)<150)] was achieved by 10 HSCT patients versus two control patients at final evaluation. Active disease, evaluated through endoscopy and radiology, was not detected in eight patients from the HSCT group versus two patients in the control treatment.
In terms of safety, 76 serious adverse events were reported in the HSCT group, and 38 in the control group. One patient undergoing HSCT died during the trial.
Through statistical analysis, researchers found no evidence of significant sustained improvement in patients undergoing HSCT. The team concluded in their article, “Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease.”
The researchers add, however, that further study may be warranted. “It is possible that optimal sustained remission after HSCT may require maintenance immunosuppressive therapy. It is also possible that patients will regain responsiveness to treatments to which they were previously refractory. Therefore, future trials should assess the benefit of maintenance therapy. Toxicity will remain the most significant barrier to HSCT in patients with Crohn disease.”