Preventive Strategies & Novel Treatments for RA

Novel Treatments

The final portion of the lecture discussed novel therapies for RA. With chimeric antigen receptor (CAR) T cell therapy clearly on everyone’s mind, Dr. van der Woude noted this mode of treatment represents a promising, potentially long-lasting intervention for the disease.

Based on at least one case in the literature, the fact that ACPA levels decline following CD19-CAR T cell treatment implies that ACPA autoreactivity resides in the CD19 cellular subset.¹⁴ Innovative constructs, such as a new, autologous, fourth-generation CD19-targeted CAR T cell that secretes antibodies against interleukin (IL) 6 and tumor necrosis factor (TNF) α, are also being tested.¹⁵ However, Dr. van der Woude reminded the audience that the conditioning regimen and costs associated with CAR T cell therapy may still be barriers to this therapy being used for RA on a broader scale.

Bispecific T cell engagers, or BiTEs, also represent a novel therapy for patients with RA. BiTEs can simultaneously bind to T cells—typically via CD3—and a disease-relevant target, such as an autoantigen or a cell-surface molecule on autoreactive B or T cells, thereby bringing T cells into close proximity with pathogenic immune cells. This approach leads to targeted cytotoxicity or immune modulation of the autoreactive population while sparing non-pathogenic cells.

 Dr. van der Woude’s key takeaways on BiTEs are:

1. They appear to be effective and capable of deep B cell depletion in tissue;
2. They may be an option for treatment-resistant patients;
3. They have an effect that is not long lasting and, thus, may require re-treatment; and
4. They are still finding their place in the therapeutic landscape.

Among other potential new therapies in RA are S1PR1 agonists, PD1 agonists (note: development was halted for peresolimab, other agents are being investigated) and FcRn blockers, such as nipocalimab.

Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

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