Original articleAlimentary tractA Phase 2 Study of Allogeneic Mesenchymal Stromal Cells for Luminal Crohn's Disease Refractory to Biologic Therapy
Section snippets
Study Overview
This phase II study was an open-label, multicenter, Australian, nonrandomized evaluation of subjects with active luminal CD (CD activity index [CDAI], >250) who had failed anti-tumor necrosis factor therapy. Subjects received 4 MSC infusions (2 × 106 cell/kg body weight) each 1 week apart (Figure 1). The primary outcome measure was clinical response (CDAI reduction, >100 points) at day 42; secondary outcome measures at day 42 were clinical remission (CDAI, <150), endoscopic improvement (CD
Demographics
This study included 16 patients, aged 21 to 55 years (7 men), with a mean CDAI of 371 (range, 256-603). Thirteen patients had Crohn's colitis, 2 patients had ileocolitis, and 1 patient had ileal disease alone (Table 1). Three patients had primary failure of a single biologic; the remainder failed both infliximab and adalimumab. The most recently administered biologic was between 4 and 8 weeks before MSC administration in 11 patients (adalimumab, n = 10; infliximab, n = 1), and between 8 weeks
Discussion
This phase II study suggests efficacy of intravenous allogeneic MSCs in luminal CD. In 15 patients with moderate to severe active disease, refractory to anti-tumor necrosis factor therapy, 4 infusions of 2 × 106 cell/kg at weekly intervals led to clinical response in 12 patients (80%), clinical remission in 8 patients (53%), and endoscopic improvement in 7 patients (47%). Quality of life improved, in parallel with improvement in CDAI.12 Locally injected allogeneic MSCs are effective in perianal
Acknowledgments
The authors acknowledge and thank the following: Janina Pawlik, Janice Fogarty, Kath Shaw, Lisa Kaminskis, Adrian Pannekoek, and the staff of the Department of Haematology at The Alfred Hospital.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Broad Medical Research Program of The Broad Foundation, and Therapeutic Innovation Australia (formerly Research Infrastructure Support Services, Inc).