Background/Purpose: Mesenchymal stem cell (MSC) therapy represents a promise for the treatment of autoimmune diseases due to its potent immunomodulatory effect. We investigated the long-term safety of a single treatment of human umbilical cord blood-derived (hUCB)-MSCs in patients with rheumatoid arthritis (RA).

Methods: Patients with RA who met the 2010 ACR/EULAR classification criteria and received a single intravenous infusion of hUCB-MSCs (3 groups; 2.5 x 10⁷, 5.0 x 10⁷, 1.0 x 10⁸ cells) in a phase I trial (NCT02221258) entered this 5-year observational study. Safety assessments were carried out at 3, 6, and 12 months for the first year after the hUCB-MSC administration and annually thereafter for the remaining period. Key safety endpoints included overall adverse events (AEs), serious adverse events (SAEs) and AEs of special interest including infection, thromboembolism, and benign/malignant tumor. Physical examination, laboratory tests and electrocardiograms were also performed.

Results: A total of nine patients were treated after the phase I trial at a single center. The most frequent AEs (Table) over 5 years were osteoarthritis (66.7%), nasopharyngitis (44.4%), abdominal pain (33.3%), osteopenia or osteoporosis (33.3%), lumbar spinal stenosis (22.2%), and hypertension (22.2%). SAEs occurred in 5 patients (55.6%); a serious infection (cellulitis) happened in one patient in the 1.0 x 10⁸ group that resolved after treatment. Three years after administration of MSCs, a benign ovarian tumor and a breast adenoma were reported in the 2.5 x 10⁷ and 5.0 x 10⁷ groups, respectively. However, no death, thromboembolism or malignancy occurred during the follow up period. The incidence of AEs increased over time after administration of MSCs, but similar across the dose groups. There were no clinically significant laboratory finding, except for a case of hypertriglyceridemia and a case of anemia.

Conclusion: The long-term safety profile of a single dose of intravenous hUCB-MSC in patients with RA was reasonable and acceptable.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-safety-of-a-single-infusion-of-human-umbilical-cord-blood-derived-mesenchymal-stem-cell-therapy-in-rheumatoid-arthritis-the-5-year-follow-up-of-the-phase-i-clinical-trial/