Letter: Real-Life Evaluation of Effectiveness of Mesenchymal Stem Cell Treatment in Fistulising Crohn's Disease Emphasises Importance of Appropriate Patient Selection and Centre Expertise—Authors' Reply

Abstract

We are grateful to Drs. Gao and Segal for their letter concerning our article [1, 2]. As pointed out, patient selection, concurrent medication and an experienced medical centre are the important pillars of successful outcomes of mesenchymal stem cell (MSC) treatment in perianal fistulising Crohn's disease (PFCD). Despite the evolving evidence, it is still unclear whether MSC treatment should be used early or late in the disease process, how can we optimise patients prior to receiving stem cell therapy and whether there are any clinical or biochemical predictors of treatment success [3].

Conflicting results between ADMIRE trials with real-life data highlight the need to better understand the factors associated with successful treatment. However, our results suggest that, as in case of luminal CD [4], early intervention in PFCD is crucial for improving therapeutic outcomes. Furthermore, analysing the discrepancies between ADMIRE results emphasises the importance of population characteristics, as pointed out by Drs. Gao and Segal. An additional important consideration is that the inclusion of milder cases, compared to the ADMIRE trials, is likely to significantly enhance the effectiveness of darvadstrocel. Based on this, we believe that appropriately positioning a clinically proven, effective therapy is certainly a better alternative than completely abandoning an option that, according to real-world data, provides a significant improvement in quality of life for most patients in a highly restrictive setting.

The growing therapeutic arsenal for inflammatory bowel disease clearly underscores the need for patient care in centres with well-trained specialists who have appropriate expertise in the management of difficult-to-treat patients. This applies not only to the use of biological therapies and small molecules but also to the application of darvadstrocel for treating PFCD.

We agree with Drs. Gao and Segal that further well-designed, real-world clinical studies are needed to better define the role of MSC therapy and help to position it within the treatment protocols for PFCD.