Research in context
Evidence before this study
We searched PubMed from Jan 1, 1980, to Dec 31, 2015, for publications on the treatment of complex perianal fistulas in patients with Crohn's disease using the following search terms: “perianal”, “fistul*”, “Crohn's disease”, and “treatment”. This search yielded 639 results, of which 52 were clinical studies. These studies showed that: (1) existing pharmacological treatments for complex perianal fistulas have low efficacy in inducing fistula healing (antibiotics 21–48%; thiopurines 20–40%; anti-tumour necrosis factor [TNF] treatment 23% complete responders [36% of 64% of patients who responded to induction treatment]); (2) the only approved drug that has shown efficacy in a randomised clinical trial is the anti-TNF drug infliximab; and (3) few treatment options exist for drug-treatment-refractory patients, and repeated surgical options are associated with substantial morbidity (eg, incontinence) and with a significant risk of permanent stoma. These findings emphasised the need for novel treatment options for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Available data suggest that Crohn's-disease-associated fistulas originate from an epithelial defect that might be caused by ongoing inflammation. Since adipose-derived mesenchymal stem cells have anti-inflammatory and immunomodulatory potential, they seem to be suitable candidates to treat this disorder. Initial clinical results suggested they might have therapeutic potential in this setting.
Added value of this study
This study is, to our knowledge, the first randomised, placebo-controlled study of adipose-derived mesenchymal stem cells (Cx601) for the treatment of complex treatment-refractory perianal fistulas in patients with Crohn's disease. Our findings suggest that local treatment with Cx601 added on to established treatments for Crohn's disease might open new therapeutic options for refractory perianal disease. In this study, we assessed therapeutic effect using an innovative and distinctive primary endpoint combining both clinical assessment of fistula closure and MRI. 50% of patients treated with Cx601, compared with 34% of the placebo group, achieved combined remission 24 weeks after treatment, and the stem-cell treatment was well tolerated.
Implications of all the available evidence
Our findings suggest that Cx601 might offer patients with Crohn's disease who have treatment-refractory complex perianal fistulas a novel and minimally invasive closure alternative to avoid the need for systemic immunosuppression or surgery.