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* = Presenting author

P590. Allogeneic mesenchymal stromal cells for biologic refractory luminal Crohn's disease

G. Forbes1, M. Sturm1, R. Leong2, M. Sparrow3, D. Segarajasingam4, A. Cummins5, R. Herrmann1, 1Royal Perth Hospital, Perth, Australia, 2Concord Hospital, Sydney, Australia, 3The Alfred Hospital, Melbourne, Australia, 4Sir Charles Gairdner Hospital, Perth, Australia, 5The Queen Elizabeth Hospital, Adelaide, Australia

Background

Sustained benefit of medical therapy is achieved in less than two-thirds of Crohn's disease (CD) patients. Cellular therapy in the form of bone marrow or peripheral blood stem cell transplantation, either allogeneic or autologous, has been successfully used in small numbers of patients, but with the need for prior myeloablative therapy or hematopoietic stem cell mobilisation. By contrast, mesenchymal stromal cells (MSC) are multipotent adult stem cells, which are not immunogenic and escape immune recognition; myeloablation is not required prior to infusion for potential therapeutic efficacy. The aim of this study (NCT01090817) is to establish efficacy and safety of allogeneic MSC in luminal Crohn's disease.

Methods

A phase II open label Australian multicentre study in patients (planned n = 30) with infliximab/adalimumab-refractory moderate to severe, endoscopically confirmed, active luminal CD (CDAI >250). Marrow derived MSC are isolated, culture expanded and cryopreserved at Royal Perth Hospital, and transported at <−150°C to study centres. Subjects receive intravenous allogeneic MSC (2 million cells/kg body weight) weekly for 4 weeks. The primary study endpoint is clinical response (decrease in CDAI >100 points) at day 42; secondary endpoints at day 42 are clinical remission (CDAI <150), endoscopic improvement (CDEIS fall >5 or CDEIS <3) and safety. Prior to enrolment, biologics are not permitted within 4 weeks; corticosteroids or immunomodulators are permitted at stable dose between day −14 and day 42.

Results

To November 2012, outcome data are available for 14 patients (aged 21 to 55 years; 6 males); 13 patients have completed the 42-day study; one withdrew for worsening CD. Mean/median CDAI (n = 13) fell from 373/335 (range 256–603) at entry to 179/128 at day 42 (p = 0.001). Mean CDAI fell weekly, after each MSC infusion (day 0: 373; day 7: 245; day 14: 222; day 21: 185; day 28: 158; day 42: 179).

Of the 14 patients, clinical response occurred in 12 (mean CDAI reduction: 211, range 102–367), clinical remission in 8 (mean CDAI at day 42: 94, range 44–130), and endoscopic improvement in 7 (mean CDEIS 21.5 [range 3.3–33] to 11.0 [0.3–18.5]). No significant adverse events have occurred.

Conclusion

Allogeneic MSC have therapeutic efficacy and appear safe in luminal CD. These data provide justification for studies of long term efficacy and safety, use in earlier stage disease, and optimal induction or maintenance dose scheduling.