September's paper of the month is a prospective interventional study on 21 patients with perianal fistulous disease whose treatment included injection of freshly collected autologous adipose tissue.
Efficacy of injection of freshly collected autologous adipose tissue into perianal fistulas in patients with Crohn’s disease
Anders Dige, Helene Tarri Hougaard, Jørgen Agnholt, Bodil Ginnerup Pedersen, Michaela Tencerova, Moustapha Kassem, Klaus Krogh, Lilli Lundby
Gastroenterology 2019;156:2208-16.e1
What is known on the subject
Perinanal disease is common in patients with Crohn’s disease and represents a significant disease burden in terms of quality of life. Despite the introduction of biological treatments and recognition of combined medical and surgical input to achieve optimal healing, well over 50% of patients will continue with symptoms.
Recent advances in treatment have included the use of mesenchymal stem cells. One large multicenter phase 3 trial has reported that treatment with in-vitro expanded allogenic adipose-derived stem cells in patients resistant to biological therapy resulted in a closure rate of 50% compared with 34% in the placebo group at 24 weeks after treatment [1] and that this was maintained after 52 weeks [2]. The stem cells were produced commercially and are now available throughout most of Europe.
Despite this exciting advancement in treatment, very significant cost and logistical implications remain. Freshly collected adipose tissue may represent a faster, easier and more cost effective alternative to in vitro expanded autologous or allogenic stem cells.
What this study adds
This was a prospective interventional study on 21 patients with perianal fistulous disease. All patients had quite aggressive surgical treatment in the form of repeated curettage every 6-8 weeks until the secretory activity of the fistula was reduced. At this stage adipose injection was carried out. The collection of fresh autologous adipose tissue using liposuction was relatively simple. Those that failed to have complete healing at 6 weeks underwent repeat injection. The primary end point at 6 months after treatment was well-defined. After single or repeat injections 57% achieved clinical healing and 90% of those who underwent MRI had radiological evidence of healing. The intervention appeared safe.
Implications for colorectal practice
Recent publications on the use of stem cells for the treatment of perianal fistulous disease have illustrated the potential for this particular treatment to help some patients achieve disease remission. There is a common theme of the need for vigorous surgery and it could be argued that meticulous, persistent and aggressive surgery rather than stem cell injection is the key to success in these patients. A well defined clinical and radiological outcome such as shown in this study is essential if results are to be robust.
These findings clearly require further confirmation in a blinded comparative trial with a control of either placebo or alternatively the commercially available stem cells. A comparative trial against placebo may be difficult in terms of blinding both surgeon and patient given the need for liposuction and novel methods of study design would have to be incorporated. The control of commercially available stem cells would probably be easier form a methodology perspective but more difficult in terms of cost. Nevertheless, if proved to be non-inferior to the commercially available treatment, this has significant implications in terms of a viable cost-effective option of patients with treatment resistant perianal fistulous Crohn’s disease.
References
- Panes, J., Garcia-Olmo, D., Van Assche, G. et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016; 388: 1281–1290.
- Panes, J., Garcia-Olmo, D., Van Assche, G. et al. Long-term efficacy and safety of stem cell therapy (cx601) for complex perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2018; 154: 1334–1342.e4