Background/Purpose: Mesenchymal stem (stromal) cells (MSCs) constitute an emerging therapeutic strategy for several human diseases. Small non-randomized studies have shown that MSCs may be a promising treatment for Rheumatoid Arthritis (RA), potentially acting to ”reset” the immune system to a “pre-RA” state. A single infusion of bone marrow derived allogeneic MSCs has been shown to be safe in a phase 1 randomized double blind controlled trial in early RA patients. We have previously reported the safety of allogeneic MSCs in early RA. A secondary goal was to evaluate patient reported outcomes (PROs). Here we compare PROs and measures of disease activity.

Methods: A prospective, double blind, placebo-controlled interventional study to evaluate the safety of allogeneic mesenchymal stem cell infusion in early RA patients with moderate to high disease activity was conducted. Patients were followed for 52 weeks following MSC infusion as required. Disease Activity Score 28 – C-Reactive Protein (DAS28-CRP) and patient reported outcomes using Patient-Reported Outcomes Measurement Information System (PROMIS) measures were completed as exploratory endpoints. PROMIS measures included Physical Function, Ability to Participate in Social Roles and Activities, Anxiety, Depression, Fatigue, Pain Interference, Sleep Disturbance, Pain Intensity. The Wilcoxon Signed Rank test was used to compare the change in these measures between visits 2 (baseline, day 0 before infusion) and visit 6 (day 28 post infusion).

Results: 10 patients were recruited, 8 patients received MSC (5 at 1M/kg ideal body weight and 3 at 4M/kg) and 2 patients received placebo. When comparing the 8 patients treated with MSC before and after infusion, 3 categories of PROMIS scores and DAS28-CRP had a statistically significant improvement at 28 days. The PROMIS scores that improved were: Physical Function median T score increased from 41.30 to 44.70 (p = 0.047), Fatigue decreased from 62 to 53.10 (p = 0.034), and Pain Interference was also reduced from 63.70 to 57.70 (p = 0.047). DAS28-CRP decreased from a median score of 4.78 before MSC to 3.19 after MSC (p=0.007813).

Conclusion: This study is the first randomized double blind clinical trial of allogeneic MSCs in early RA and suggested that MSC infusion may result in improvement in patient reported outcomes using PROMIS measures, as well as in disease activity as measured by DAS28-CRP. These preliminary efficacy results provide a proof of concept that warrant performance of a phase 2 trial to provide evidence as to whether MSCs can treat early RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/patient-reported-outcomes-and-disease-activity-from-a-phase-1-double-blind-randomized-clinical-trial-of-allogeneic-mesenchymal-stem-cells-in-early-rheumatoid-arthritis/