The findings of a phase II study show that the injection of adipose-derived stem cells into complex perianal fistulas related to cryptoglandular disease or Crohn's disease resulted in healing in 71% of patients. In contrast, healing occurred in only 16% of patients treated with standard therapy using fibrin glue.WASHINGTON (Reuters Health) May 24 - Rosiglitazone (Avandia, GlaxoSmithKline) effectively relieved symptoms of refractory ulcerative colitis in nearly half of patients treated in a study reported here this week during Digestive Disease Week 2007.
This news comes in the midst of controversy stemming from a meta-analysis published this week in The New England Journal of Medicine, linking the oral anti-diabetic agent to a 43% increase in risk of myocardial infarction. As a result, the Food and Drug Administration (FDA) is currently re-reviewing the GSK drug.
Rosiglitazone, approved for the treatment of type 2 diabetes, is a thiazolidinedione ligand for gamma subtype of peroxisome proliferator-activated receptors.
Dr. James D. Lewis of the University of Pennsylvania in Philadelphia and colleagues examined rosiglitazone's anti-inflammatory properties in 105 patients with mild-to-moderate ulcerative colitis refractory to or intolerant of standard therapy with 5-aminosalicylic acid.
Patients were randomized to active therapy with rosiglitazone 4 mg bid or placebo bid for 12 weeks.
At baseline, patients had scores of 4-10 on the Disease Activity Index (DAI), indicating mild-to-moderate disease. Clinical response was defined as a reduction of 3 or more points and clinical remission as a reduction of 2 or more points on the DAI by the 12th week.
At the end of the study period, 44% of patients on rosiglitazone had a drop of 2 or more points on DAI compared with 23% of patients on placebo. Clinical remission occurred in 17% of patients on active treatment and in only 2% of patients on placebo.
Endoscopic remission, with no evidence of mucosal activity, occurred in 8% of patients on active treatment and in 2% of patients on placebo. Neither group had a statistically significant response on endoscopy, but Dr. Lewis noted that numerically, there was a response in this very small cohort.
Stool frequency, bleeding rates and the physician's global assessments of patients on active therapy all improved.
"We saw a clinical response within 4 weeks" of beginning rosiglitazone therapy, Dr. Lewis told meeting attendees.
Serious adverse events were "rare and did not differ between the placebo and rosiglitazone arms," he reported.
If patients don't respond to or can't take 5-aminosalicylic acid, "rosiglitazone is a novel second-line therapy," Dr. Lewis said.
As far as the report of increased risk of MI with the drug, GSK has issued a statement saying it "strongly disagrees with the conclusions reached in the NEJM article...the findings are based on incomplete evidence and a methodology that the author admits has significant limitations."
In an interview with Reuters Health after his presentation at DDW, Dr. Lewis said "this study was an investigator-sponsored study funded principally by the NIH. I cannot speak for GSK's plans with regards to this field of research. We are considering future investigator-initiated studies (in ulcerative colitis patients), but will decide if and how to proceed when we have had more time to explore the information available on the risk of MI with rosiglitazone."
"We need another treatment for these patients," principal investigator Dr. Damian Garcia-Olmo of La Paz University Hospital in Madrid, told Reuters Health, after presenting the results of his group's study here during Digestive Disease Week 2007, a conference jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract.
The study involved 49 adults with complex perianal fistulas. The investigators extracted fat tissue and expanded adipose-derived mesenchymal stem cells in culture for approximately 3 months.
At that point, patients were randomized to treatment with fibrin glue or to fibrin glue plus stem cells injected into the interior of the fistula. Healing was assessed 8 weeks later, defined as re-epithelialization of the fistula opening and the absence of drainage either spontaneously or on gentle compression.
If healing was incomplete at 8 weeks, patients were retreated with fibrin glue or fibrin glue plus stem cells.
At follow-up, 17 of the 24 patients (71%) who received stem cells had evidence of healing compared with only 4 of 25 patients (4%) treated with fibrin glue alone. "We define a cure as complete healing, and there was a significantly higher cure rate with the stem cells," Dr. Garcia-Olmo said.
The stem cells spurred healing through immunoregulation and cell proliferation without resorbing the fibrin glue, Dr. Garcia-Olmo told meeting attendees.
"Our main concern in this phase II study was safety, and that was not a problem," he noted.
While the exact duration of response is unknown, some patients have been followed for up to 4 years and fistulas have not recurred. "This is fantastic!" Dr. Garcia-Olmo exclaimed. "It's very, very durable, and the stem cells stay where they are put."
Phase III trials have already begun.