Crohn's Disease

Through week 104, 7 treatment-emergent serious adverse events were reported, of which 4 occurred between weeks 52 and 104. At week 104, clinical remission was reported in 14/25 (56%) patients in the darvadstrocel group and 6/15 (40%) patients in the control group.

All patients tolerated the mesenchymal stromal cell infusion well and no dose limiting toxicity was seen. Seven patients had serious adverse events of which five were hospitalisations for Crohn's disease flare. Two of these serious adverse events were possibly related to the mesenchymal stromal cells infusion. Five subjects showed clinical response 2 weeks after the infusion. Mesenchymal stromal cell phenotype, cytokine responsiveness, and peripheral blood mononuclear cell proliferation blockade were not different among the patients.

In the study, 15 patients showed a significant reduction in mean CDAI score from 370 to 203 at day 42 after MSC infusion, with scores decreasing after each infusion. 80% of patients had a clinical response, with 53% achieving clinical remission. 7 patients had endoscopic improvement, and one patient experienced a serious adverse event (2 dysplasia-associated lesions), which was unlikely caused by MSCs.

MSC injections were well tolerated but four hospitalisations for occlusion were reported. At W12, five patients presented a complete or partial resolution of the stricture [two complete and three partial]. Seven patients were re-evaluated at W48 [one dilated, one operated, and one lost to follow-up] and four patients had a complete resolution. The evolution of clinical scores between W0, W12, and W48 was not statistically significant.MSCs injection in CD stricture was well tolerated and may offer a benefit.

At 6 months, 31% of the treatment group and 20% of the control had complete clinical and radiographic healing. When stratifying the treatment group into perianal [n = 7] and ano-vaginal [n = 8] fistulas, 6-month healing in the treatment groups was 57% and 0%, respectively. The perianal Crohn's disease activity index [PCDAI], Wexner incontinence score, and van Assche score all significantly decreased in treatment patients at 6 months; only the PCDAI decreased in the control group. one marrow-derived, allogeneic MSCs offer a safe and effective alternative treatment approach for peripouch fistulas in the setting of a Crohn's like phenotype of the pouch.

Seventy percent of patients had a clinical response at week 12, and 80% at week 48; 20% and 60% of patients achieved combined remission at weeks 12 and 48, respectively. In addition, 13 of 17 treated external openings showed complete re-epithelialization or an absence of drainage at week 48. Two patients showed complete occlusion of fistula tracts on magnetic resonance imaging at week 48 (Figure 1A). A significant improvement in perianal disease severity was observed with a decreased PDAI score (7.3 at baseline, 3.8 at week 12 and 3.4 at week 48;P= .002) and an increased quality of life score (P= .038)

212 patients were randomly assigned: 107 to Cx601 and 105 to placebo. A significantly greater proportion of patients treated with Cx601 versus placebo achieved combined remission in the ITT (53 of 107 [50%] vs 36 of 105 [34%]; difference 15·2%, 97·5% CI 0·2-30·3; p=0·024) and modified ITT populations (53 of 103 [51%] vs 36 of 101 [36%]; 15·8%, 0·5-31·2; p=0·021). 18 (17%) of 103 patients in the Cx601 group versus 30 (29%) of 103 in the placebo group experienced treatment-related adverse events, the most common of which were anal abscess (six in the Cx601 group vs nine in the placebo group) and proctalgia (five vs nine).Cx601 is an effective and safe treatment for complex perianal fistulas in patients with Crohn's disease who did not respond to conventional or biological treatments, or both.

Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [n = 4] 63%, and in cohort 3 [n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy