Combination of mesenchymal stem cell transplantation (MSCT) with interferon-γ (IFN-γ) is a promising treatment approach for patients with rheumatoid arthritis (RA) refractory to conventional and/or biological disease-modifying antirheumatic drugs (DMARDs), according to study results published in Annals of the Rheumatic Diseases.

RA is the most common inflammatory rheumatic disease. And despite the success of biological agents in RA, a significant portion of patients are not responsive to these drugs. Hence, novel treatment strategies are required for patients with refractory disease.

Mesenchymal stem cells have significant immunomodulatory properties with demonstrated immunosuppressive and anti-inflammatory effects. For that reason, this is considered a promising treatment strategy for various autoimmune diseases. The goal of the current study was to assess the outcomes of IFN-γ combined with MSCT in patients with RA.


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The researchers assessed the efficacy of MSCT plus IFN-γ in a RA mouse model of MSCT monotherapy or in combination with IFN-γ and in a clinical study of 63 patients with RA with a poor response to conventional synthetic or biological DMARDs, non-steroidal anti-inflammatory drugs, or steroids.  The participants were randomized to 2 treatment groups: MSCT plus IFN-γ or MSCT monotherapy.

The participants completed 48 weeks of follow-up and were assessed at various time points. The primary outcome was efficacy, defined as good or moderate European League Against Rheumatism (EULAR) response rate and the percentage of patients attaining American College of Rheumatology 20 (ACR20) response at 3 months.

According to the murine models, treatment with MSCT without IFN-γ did not improve clinical severity of arthritis in mice and in fact, was associated with severe arthritis symptoms and worse synovitis and cartilage destruction on histological evaluation, while the combination of MSCT with IFN-γ led to a significant improvement of arthritis. Furthermore, combination of mesenchymal stem cells with IFN-γ had a suppressive effect on T cell proliferation, but this was not seen with MSCT monotherapy.

Similarly, in the clinical study, combination of MSCT with IFN-γ was associated with a rapid clinical improvement and a higher efficacy rate compared with MSCT monotherapy (93.3% vs. 53.3%, respectively). In addition, a higher percentage of patients treated with MSCT and IFN-γ had an ACR20 response at 3 months (93.3% vs. 40.0%, respectively; P <.05).

During or after MSCT or MSCT plus IFN-γ treatment there were no severe acute adverse events or unexpected safety issues. 

Study limitations include the small sample size and the researchers call for additional studies.

“We proposed a novel clinical strategy for the treatment of RA with MSCT+IFN-γ and confirmed that MSCT+IFN-γ combination therapy synergistically enhances the efficacy of MSCT in patients with RA without any side effects during a 1-year observation period,” concluded the researchers.

Reference

Xu X, He X, Yang Y, et al. Combination of human umbilical cord mesenchymal stem (stromal) cell transplantation with IFN-γ treatment synergistically improves the clinical outcomes of patients with rheumatoid arthritis [published online Jun 19, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-217798