AURORA, COLO. — Perianal Crohn’s disease with fistula is notoriously difficult to treat and can make patients’ lives miserable, but a new, minimally invasive approach involving local injection of mesenchymal stem cells is both safe and, in a significant proportion of patients, highly effective, according to a colorectal surgeon.
“It’s a really debilitating phenotype, a spectrum of phenotypes,” Amy Lightner, MD, of the Cleveland Clinic said at the annual Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Although some patients have minimal symptoms, others may require multiple setons to aid in drainage and healing, while others may require fistulotomy, endorectal advancement flap, intersphincteric fistula tract (LIFT) procedure, diversion, or proctectomy.
“Why is it so difficult to treat? Well, part of it is that this is an anatomic defect, and this is why 90% of patients will come to the operating room and will see their surgeons on a frequent basis. The other part of that is that we have medical therapies to treat these fistulas but they’re really largely ineffective, because there is that anatomical defect, the hole there that needs to be closed,” Dr. Lightner said.
Up to 20% of patients may require a permanent stoma, and an additional 20% may require temporary fecal diversion.
Mesenchymal stem cells (MSC) are derived from bone marrow, fat stores, or umbilical cord tissues. Unlike embryonic stem cells, which have the ability to metamorphose into a multitude of other cell types, mesenchymal stem cells are differentiated “adult” cells.
They work by secreting anti-inflammatory cytokines and recruiting immune cells to stimulate tissue repair and healing. The cells are delivered in a minimally invasive outpatient setting, and there is no risk of incontinence compared with more invasive procedures such as fistulotomy or advancement flaps.
Effective and safe
MSCs were first used in Spain in 2003 to successfully treat a young women with a complex fistula with five perianal tracts converging into a rectovaginal fistula. The investigators injected a single dose of 9 x 106 MSCs into the site, and the fistula healed within 3 months.
Since then in multiple clinical trials involving more than 400 patients, injection of MSCs has resulted in fistula closure and complete healing by 8-12 weeks in 50%-85% of patients, Dr. Lightner said.
The treatment effect is also durable, she said, pointing to data from the ADMIRE-CD study, in which 51.5% of Crohn’s disease patients with treatment-refractory complex perianal fistula were healed at 24 weeks following injection of adipose-derived stem cells, compared with 35.6% of controls. At 1 year of follow-up, respective rates of healing were 56.3% vs. 38.6%.
Dr. Lightner also cited a case report of a patient whose fistula remained healed 4 years after receiving MSCs for refractory perianal Crohn’s fistulas.
Although MSCs are derived from healthy donors, they do not bear cellular surface antigens that would instigate a destructive host immune response, and to date, there have been no reports from clinical trials of systemic infections or complications. The most frequently reported adverse events have been injection-site pain in about 12%-15% of patients, and perianal abscess in 5%-13%, with similar frequencies in treatment and control groups.
Dr. Lightner and colleagues are currently exploring additional indications for stem cell therapy with MSCs, including other complex fistula phenotypes, intestinal Crohn’s disease, and ulcerative colitis.
In a separate presentation, James D. Lewis, MD, MSCE, of the University of Pennsylvania in Philadelphia talked about what would be needed to achieve a “medical moonshot” with the goal of curing inflammatory bowel disease (IBD), and touched on hematopoietic stem cell transplants as a potential option for patients with chronic, severe, and intractable disease.
One of his patients was a woman in her 60s who was diagnosed with stricturing and penetrating Crohn’s disease in her 30s, with the disease involving the ileum and entire colon. She had previously undergone three small bowel resections and a partial colon resection, and had never experienced remission despite taking steroids, azathioprine, methotrexate, four anti-TNF drugs, ustekinumab (Stelara), and vedolizumab (Entyvio).
Following an autologous hematopoietic stem cell transplant, she had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 0. Her course was complicated by demand ischemia and acute kidney injury.
An IBD specialist who was not involved in either study commented in an interview that both MSCs and stem cell transplants show promise for treatment-refractory IBD,
“Both approaches are very promising, but stem cell transplants for IBD haven’t been formally studied yet so the data aren’t as strong, but there is promise for the future,” said Berkeley N. Limketkai, MD, PhD, from the University of California, Los Angeles.
“The challenges, however, are also the morbidity associated with actually undergoing such procedures,” he continued. Short- and long-term morbidities associated with hematopoietic stem cell transplants may include mucositis; hemorrhagic cystitis; prolonged, severe pancytopenia; infection; graft-versus-host disease; graft failure; pulmonary complications, veno-occlusive disease of the liver; and thrombotic microangiopathy.
Dr. Limketkai said that over time as the protocols for stem cell transplants in IBD improve, the benefits for select patients may more clearly outweigh the risks.
Dr. Lightner’s work is supported by the Leona M. and Harry B. Helmsley Charitable Trust and the American Society of Colon and Rectal Surgery. She disclosed consulting fees from Boomerang Medical, Mesoblast Limited, Ossium Health, and Takeda Pharmaceuticals USA. Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has also served as a consultant to and data safety monitoring board member for several entities. Dr. Limketkai disclosed consulting for Azora Therapeutics.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.