624 Clinical and immune analysis of mesenchymal stromal cells (MSCs) for multiple biologic-resistant psoriasis

Biologics have transformed the management of moderate-to-severe psoriasis; however, none are curative, and an increasing number of patients have failed all available classes. MSCs, multipotent stem cells with immunomodulatory properties have been used to treat immune-mediated inflammatory diseases including rheumatoid arthritis and Crohn disease. We investigated the efficacy and safety of umbilical cord-derived MSCs in 2 adults with severe, multiple biologic-resistant psoriasis. MSCs were infused intravenously at a dose of 2.2–3x106cells/kg on Day (D) 0 and D7. Both Patient 1(46yo F, baseline PASI 37.8, DLQI 27) and Patient 2 (45yo F, baseline PASI 13.8, DLQI 15) had failed all 4 classes of biologics. At the time of infusion, Patient 1 was unresponsive to etanercept and Patient 2 failing guselkumab. Patient 1: by D7, itch reduced by 50% and by D16, PASI reduced to 23.0 (-39%) and DLQI 10. At D70, PASI maintained at 21.8. Co-morbidities included type 2 diabetes and psoriatic arthritis(PsA). PsA tender joint count at baseline 13; reduced to 9 at D16. Patient 2: by D3, itch reduced by 90%; by D7, PASI reduced to 8.2 (-41%) and DLQI 12. At D28 PASI 1.8 (-87%) and DLQI 8. MSC infusions were well tolerated without adverse events. For Patient 1, immunophenotyping of peripheral blood mononuclear cells at baseline, D7 and D42 post-infusion revealed changes in myeloid and lymphoid cell compartments. Frequency of myeloid dendritic cells(p<0.01 at D7 and D42) and monocytes(p<0.01 at D42) significantly decreased over time, with the latter shifting from classical to non-classical phenotype (p<0.05 at D42). Frequency of CD8+CLA+CD103- skin homing T cells displaying a mixed T1/T17 phenotype significantly increased by D42 (p<0.05), suggesting reduced skin homing by pathogenic T cells. Taken together, MSCs appear to have changed the peripheral immune profile. In conclusion, these data are supportive of immunomodulation by and efficacy of MSCs for patients with severe psoriasis unresponsive to multiple lines of biologics.