Safety and efficacy of intravenous administration of bone-marrow derived mesenchymal stromal cells in therapy refractory juvenile idiopathic arthritis patients, a phase IB/IIA pilot-study

Objectives: To compare the total number of adverse events (AE's) before and after mesenchymal stromal cell (MSC) infusion in refractory JIA and to evaluate its effectiveness. Methods: Single-centre Phase Ib/IIa, open label intervention study in JIA patients previously failing all biologicals registered for their diagnosis. Six patients will receive 2 million/kg intravenous infusions of allogeneic bone-marrow derived MSC. In case of ACR-Ped30-response but subsequent loss of response one and maximal two repeated infusions are allowed. Results: Six JIA patients with 9.2 years median disease duration, still active arthritis and damage were included. All had failed methotrexate, corticosteroids and median 5 different biologicals. MSC were administered twice in 3 patients. No acute infusion reactions were observed and a lower post-treatment than pre-treatment incidence in AE's was found. The one sJIA patient had again an evolving macrophage activation syndrome, 9 weeks after tocilizumab discontinuation and 7 weeks post- MSC infusion. Eight weeks after one MSC infusion, 4 patients showed less active joints, 5 patients improved in many clinical parameters and inflammatory parameters decreased in 3/4. After 1 year, we found significantly lower active joint counts, improved well-being scores, normalised median ESR- and CRP-levels. Inactive disease was reached by 3 patients at 1 year. Conclusions: MSC infusions in refractory JIA patients are safe, although in sJIA stopping the 'failing' biologic treatment carries a risk of a MAS flare since the drug might still suppress the systemic features. Furthermore, intravenous administration of MSC might be efficacious even in multiple biological-failing JIA patients with damage.