Stem cells may help patients with refractory Crohn's disease

Reuters Health Information: Stem cells may help patients with refractory Crohn's disease

Stem cells may help patients with refractory Crohn's disease

Last Updated: 2016-08-15

By Lorraine L Janeczko

NEW YORK (Reuters Health) - Mesenchymal stem cells (MSCs) may help treat complex perianal fistulas in patients with Crohn's disease who don't respond to conventional or biological treatments, new research shows.

In a trial involving more than 200 patients, allogeneic, expanded, adipose-derived mesenchymal stem cells (Cx601) added to conventional treatments helped patients with refractory complex perianal fistulas avoid systemic immunosuppression or surgery.

"Roughly 90% of the patients in this study were refractory to the most potent therapies we have to treat perianal fistulizing Crohn's disease, including immunosuppressants and anti-TNF (anti-tumor necrosis factor) drugs," said lead author Dr. Julian Panes of the Hospital Clinic de Barcelona, Spain.

"MSCs led to a significantly higher rate of fistula closure, and many patients experienced complete closure in just two weeks," Dr. Panes, also of the University of Barcelona, told Reuters Health by email. "The treatment also led to the absence of abscesses on MRI, which is important because abscesses are associated with greatly increased rates of fistula recurrence."

Dr. Panes and his colleagues conducted a randomized, double-blind study over about three years at 49 hospitals in seven European countries and Israel to investigate combined remission 24 weeks after treatment.

The primary endpoint was the clinical assessment of closure of all treated external openings that were draining at baseline and the absence of collections greater than 2 cm of the treated perianal fistulas, confirmed by MRI. The team assessed efficacy in intention-to-treat (ITT) and modified ITT populations and examined safety in a safety population.

As reported in The Lancet, online July 28, 107 patients were treated with a single intralesional injection of 120 million Cx601 cells and 105 received a 24-ml saline solution placebo.

Fifty percent of patients in the ITT population treated with Cx601 and 34% in the placebo group achieved combined remission at 24 weeks (p=0.024). In the modified ITT population, the numbers were 51% and 36%, respectively (p=0.021).

The stem-cell treatment was well tolerated, with 17% of patients in the active group and 29% of those in the placebo group experiencing treatment-related adverse events, most commonly anal abscesses (in six patients in the Cx601 group and nine in the placebo group), and proctalgia (in five and nine patients, respectively).

The authors note that their study excluded younger patients and those who had more than two internal and three external openings, as well as patients with other types of treatment-refractory fistulas, such as abdominal or rectovaginal, and those with previous surgery other than drainage and seton placement. Also, they did not determine whether treatment-emergent adverse events were related to Cx601 or to the preparation procedures.

"The high rate of composite remission (fistula closure and absence of abscesses) in the placebo group was unexpected," Dr. Panes said. "Various factors may have contributed to the fistula healing: patients in the placebo group underwent two surgeries - the preparation surgery with extensive drainage of the fistula tract, and the administration visit to surgically close the internal fistula orifice. Also, the medications patients received at baseline, including immunosuppressants and anti-TNF therapy, were stable over the 24 weeks of the trial, which might contribute to increased response in patients receiving placebo."

"For patients whose only or predominant manifestation of Crohn's disease is perianal, and who are not under immunosuppression, local therapy with MSCs can avoid the exposure to and risks of systemic immunosuppression," Dr. Panes said.

"Treating with autologous MSCs is limited by the time needed for adequate cell expansion, the incapability of some patients to get the necessary number of stem cells, and the great expense involved. Allogeneic MSCs induce tolerance, allowing the possible use of stem cells from a donor that would be available whenever needed, and allowing production costs to drop sharply," he added.

Drs. Rachele Ciccocioppo and Gino Roberto Corazza, of the University of Pavia, Italy, wrote in an accompanying editorial that they "regard the results of this phase 3 study as an opportunity to support the start of a new era in the treatment of fistulising Crohn's disease through local injections of an industrial preparation of MSCs (Cx601) as first-line treatment, either alone or in combination with other therapeutic drugs."

Dr. Panes added in an email that he and his group are planning a follow-up study to examine how long the benefit of Cx601 therapy can last.

TiGenix funded the study. Dr. Panes and several co-authors disclosed financial ties to the company, including employment.

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Lancet 2016.

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