Background/Purpose:

Expanded adipose-derived stem cells (eASCs) are shown to have immune-modulatory effects both in vitro and in animal models of arthritis. eASCs are currently under investigation as potential treatments targeting auto-immune and inflammatory diseases such as Rheumatoid Arthritis (RA). The aim of the study was to determine the safety, feasibility and tolerance of intravenous (IV) administration of allogeneic eASCs in RA patients.

Methods:

A 24-week, single blind dose-escalating study in RA patients under treatment with at least one non-biological DMARD and who previously failed treatment with at least two biologicals was conducted in 23 centers in Spain. Fifty-three patients with moderate to high disease activity (DAS28>3.2) were assigned to receive 1×10⁶ eASCs/kg (cohort A: 20 patients), 2×10⁶ eASCs/kg (cohort B: 20 patients), 4×10⁶ eASCs/kg (cohort C: 6 patients) or placebo (Ringer’s lactate solution: 7 patients). All patients received 3 IV eASC infusions at day 1, 8 and 15. Tolerability and treatment emergent adverse events such as Dose Limiting Toxicities (DLTs), serious adverse events (SAEs) and non-serious adverse events (AEs) were primary endpoints. ACR20/50/70, DAS 28, and SF-36 were secondary endpoints.

Results:

Patient and disease characteristics were comparable for all three dose groups. Median disease duration was 13 years Repeated IV infusion of eASCs did not show any major safety signals and the dose-limiting safety signal was not identified Three serious adverse events were reported (lacunar infarction, peroneal palsy and fever of unknown origin) of which, lacunar infarction was possibly related and lead to discontinuation with patient recovery. Most frequent non-serious AEs (threshold: > 4%) in patients treated with eASCs, included pyrexia (19%), headache (13%), urinary tract infection (13%), upper respiratory tract infection (11%), nausea (11%), malaise, respiratory tract infection, vomiting and asthenia (6% each).

In secondary endpoints, a clear dose-response effect was not observed. Maximum clinical benefit in the ITT population was observed in cohort A. ACR20/50/70 responses were observed in 45/20/5% of patients in cohort A versus 28/14/5% of patients on placebo at month 1. At month 3, ACR responses were 25/15/5 and 0/0/0 in cohort A and placebo respectively. The DAS 28 good/moderate response was 10/35% in cohort A and 0/43% in the placebo group at month 1. These values were 20/20% and 0/0% at month 3 for cohort A and placebo respectively.

Conclusion:

These early clinical results are the first to suggest that IV infusion of eASCs is well tolerated along 24 weeks and could be associated with clinical benefit in the treatment of refractory RA.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/phase-ibiia-study-on-intravenous-administration-of-expanded-allogeneic-adipose-derived-mesenchymal-stem-cells-in-refractory-rheumatoid-arthritis-patients/