A phase IB/IIA study of remestemcel-L, an allogeneic bone marrow-derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: an interim analysis

Abstract

Aim: There have been no studies into the direct injection of mesenchymal stem cells (MSCs) for luminal ulcerative colitis (UC). Our aim was to investigate the efficacy of MSCs delivered locally via endoscopic delivery, as is done in the setting of perianal disease, to treat the local site of inflammation directly.

Method: A phase IB/IIA randomized control clinical trial of remestemcel-L, an ex vivo expanded allogeneic bone marrow-derived MSC product, at a dose of 150 million MSCs versus placebo (2:1 fashion) delivered via direct injection using a 23-gauge sclerotherapy needle at the time of colonoscopy was designed to assess the safety and efficacy of endoscopic delivery of MSCs for UC. The main outcome measures were adverse events, Mayo score and Mayo endoscopic severity score at 2 weeks, 6 weeks and 3 months post-MSC delivery.

Results: Six patients were enrolled and treated; four received MSCs and two placebo. All had been on prior anti-tumour necrosis factor or anti-integrin therapy. There were no adverse events related to MSCs. In the treatment group (n = 4), the Mayo endoscopic severity score decreased in all patients by 2 weeks after MSC delivery. At 3 months, all patients were extremely satisfied or satisfied with their MSC treatment based on the inflammatory bowel disease patient-reported treatment impact (IBD-PRTI), and treatment response was described as excellent or good in all patients. In the control group (n = 2), the Mayo endoscopic severity score did not increase as a result of being off alternative therapy. At 3 months, patients were dissatisfied according to the IBD-PRTI, and treatment response was poor or unchanged.

Conclusion: MSCs may offer a safe therapeutic option for the treatment of medically refractory UC. Early data suggest improved clinical and endoscopic scores by 2 weeks after MSC delivery.

Keywords: Mayo score; mesenchymal stem cells; ulcerative colitis.

FIGURE 1

At the time of colonoscopy, a 23‐gauga sclerotherapy needle is used to inject the MSC product directly into the submucosal layer of the bowel wall.

FIGURE 2

Magnetic resonance enterography (MRE): coronal (A) and axial (B) T1‐weighted fat‐saturated postcontrast images from a baseline MRE study in a 39‐year‐old patient with ulcerative pancolitis shows diffuse colitis with wall thickening and mural hyperenhancement (arrows) but normal appearance of the distal and terminal ileum (arrowheads).

FIGURE 3

Colonoscopy: pretreatment colonoscopy with MSCs showing a Mayo score of 2 and pancolitis (A, B) as compared with the colonoscopy 3 months after MSC treatment showing a Mayo score of 0 to 1 throughout (C, D).

FIGURE 4

Mayo score in the treatment and control groups.

FIGURE 5

Mayo endoscopic severity score in the treatment and control groups.

FIGURE 6

Histopathology: all patients showed evidence of rectal epithelial injury at baseline. Three months following the endoscopic delivery of MSCs, one of four patients showed mucosal healing with mildly increased lamina propria eosinophils and no evidence of active neutrophilic inflammation.

FIGURE 7

Geboes score in treatment and control groups.