A clinical trial at UH Cleveland Medical Center will test the idea in early RA patients who haven’t responded well or who have had only an incomplete response to methotrexate therapy
UH Clinical Update - June 2018
Therapies for rheumatoid arthritis (RA) have improved dramatically in recent years. Still, there are limitations.
“What we have now are many good therapies for RA that can control the disease, but these are long-term therapies and cannot cure the disease, or place it into long-term remission,” says UH rheumatologist Donald Anthony, MD, PhD. “Most of our therapies also have the side effect of increased infection risk.”
Exploring other options, Dr. Anthony, Dr. Hillard Lazarus and their colleagues are enrolling patients at UH into a new NIH-funded clinical trial investigating the role of stem cells – specifically, mesenchymal stem cells (MSCs) – in treating RA. More than two decades ago, Dr. Lazarus helped pioneer the first-in-human clinical trials for MSCs in several settings. MSCs are able to produce a wide range of biologically active chemicals that stimulate the body’s own healing systems. Many thousands of patients now have been treated world-wide using MSCs. MetroHealth’s Nora Singer, MD, the principal investigator on the trial who will be enrolling patients at Metro, suggests that this approach has great potential.
“MSC-products secreted into fluid used to grow MSCs or “conditioned media” reduce RA effector T-cell responses ex vivo, and we hypothesize that when administered therapeutically, MSCs will induce tolerance and dampen autoreactive immune responses,” Dr. Anthony says. “Published literature and our pre-clinical studies show that bone marrow-derived MSCs may provide a new treatment for RA and act therapeutically to “reset” the immune system to a “pre-RA” state, thus reducing the need for continuous therapy.”
The prospective, double-blind, placebo-controlled trial will evaluate three different doses of MSCs for their safety. It will also test different measures of biologic efficacy using blood obtained before and after the treatment to try and understand what pathways MSCs might use to quiet RA down. Post-infusion study visits will occur on Days 1 (Visit 3), 7 (Visit 4), 14 (Visit 5), 28 (Visit 6), 56 (Visit 7), and weeks 24 (Visit 8), 39 (Visit 9) and 52 (Visit 10).
Inclusion criteria for the trial:
- Male or female age 18-80 years
- Able to give written informed consent
- Recent-onset rheumatoid arthritis – diagnosis of a year or less and symptoms for two years or less (must also meet criteria as defined per the ACR/EULAR 2010 classification criteria for RA)
- Must have detectable serum auto-antibodies against cyclic citrullinated peptides and/or high titer serum rheumatoid factor (the latter defined as > 2x ULN)
- Must have a Disease Activity Score 28 (DAS28-CRP) of > 4.4 at screening
- Must have active synovitis of at least one joint
- Must have been intolerant or had inadequate response to at least 12 weeks total of methotrexate, 10 weeks of which methotrexate must have been dosed at ?15 mg per week or with low dose corticosteroids (< 10 mg prednisone per day). Steroids must be at a stable dose for two weeks prior to infusion
- Must be clinically stable with no significant changes in health status within 2 weeks prior to randomization
For more information on this trial or to refer a patient, please contact Dr. Anthony at email@example.com.