Autologous hematopoietic stem-cell transplantation didn’t induce sustained remission of refractory Crohn’s disease in an international randomized controlled trial, which was reported online December 15 in JAMA.
Exploratory analyses of the trial data suggested that slightly more patients receiving hematopoietic stem-cell transplantation (HSCT) than usual care were able to discontinue immunosuppressive therapy, achieve nonsustained clinical remission, and show improvement in clinical and endoscopic measures of disease activity. Nevertheless, the procedure is associated with numerous and serious adverse effects. Given its failure to induce sustained remission, “HSCT is unlikely to alter the natural history of Crohn’s disease, and our findings argue against extension of HSCT to a wider group of patients outside of future additional trials,” said Dr. Christopher J. Hawkey, professor of gastroenterology at the Digestive Diseases Centre, Nottingham University, England, and his associates in the Autologous Stem Cell Transplantation International Crohn’s Disease (ASTIC) trial.
Dr. Christopher J. Hawkey
The study was conducted at 11 transplantation centers in the U.K., France, Spain, Switzerland, Italy, and Belgium and involved 45 adults with established Crohn’s disease refractory to treatment with corticosteroids and at least three immunosuppressive or biologic agents. Their disease was not amenable to surgery and continued to severely impair their everyday function and quality of life.
The study participants were randomly assigned to undergo HSCT immediately (23 patients) or to delay the procedure for 1 year (22 patients). Every 6 weeks they underwent physical examination; laboratory testing; and assessment of disease activity, adverse events, medication use, use of medical services, and effects of Crohn’s on employment. Both study groups also were assessed for quality of life at 6 and 12 months.
The primary endpoint, sustained disease remission after 12 months, was defined as a Crohn’s Disease Activity Index score of less than 150 for at least the preceding 3 months, no active treatment for at least the preceding 3 months, and no mucosal erosion or ulceration anywhere in the GI tract on endoscopy and GI imaging. Admittedly, this endpoint was stringent, but it was chosen “to reflect the benefit we judged HSCT would need to yield to justify treatment toxicity,” the investigators noted.
Only two patients in the HSCT group (8.7%) and one in the control group (4.5%) achieved the primary endpoint, which was a nonsignificant difference. There also were no differences between the two groups in quality of life as measured by the European Quality of Life Visual Analogue Scale, the EuroQoL 5 Dimensions Questionnaire, the Inflammatory Bowel Disease Questionnaire, or the Karnofsky index.
However, the data slightly favored HSCT on the secondary endpoints of decreased disease activity as measured by the Crohn’s Disease Activity Index score, the Simple Endoscopic Score for Crohn’s Disease, and the need for medical therapy or consultation. These benefits “may still be clinically meaningful in this group of patients, who have no other therapeutic options and a markedly impaired quality of life,” Dr. Hawkey and his associates said (JAMA. 2015 Dec 15. doi: 10.1001/jama.2015.16700).
The HSCT group had more frequent adverse events, particularly infections (13 vs. 0) such as neutropenic sepsis, pneumonia, and perianal abscesses. The infections included reactivations of Epstein-Barr virus, cytomegalovirus, BK virus, intestinal adenovirus, and varicella zoster virus. One patient died from infection.
“These findings do not support the widespread use of HSCT for patients with refractory Crohn’s disease,” the investigators said.