<p>Patients with systemic lupus erythematosus (SLE) have historically had limited treatment options. However, in recent years, new treatments have been approved by the US Food and Drug Administration (FDA), and several investigational agents appear to be promising. Researchers at the <strong>2024 Congress of Clinical Rheumatology (CCR) East</strong> presented data from several studies highlighting these emerging therapies.</p> <p> </p> <p><em>Following these proceedings, featured expert George C. Tsokos, MD, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Tsokos are presented here.</em></p>

These days, patients will use classical drugs for SLE, such as hydroxychloroquine and steroids, with an effort to minimize overall steroid use. For patients with more serious disease, cytotoxic immunosuppressants, including cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil, may also be used with steroids. Two biologics have recently been approved by the FDA to treat SLE. The first to be approved was belimumab, which was shown to decrease the need for steroids and, very importantly, to decrease organ damage. Then there was anifrolumab-fnia, which may prove to be particularly useful for some patients with skin manifestations.

 

Several posters presented at CCR East 2024 reported on the long-term results of anifrolumab-fnia, including 2 posters by Furie et al, 1 poster by Strand et al, and 1 poster by van Vollenhoven et al. The general findings showed that long-term treatment is beneficial. The same thing was said about belimumab. That is good news. There was also a poster presentation by Merrill et al of the phase 2 results of the upadacitinib-plus-elsubrutinib combination therapy ABBV-599. Upadacitinib is a JAK inhibitor that will limit cytokine signaling, and elsubrutinib is a BTK inhibitor that will limit B-cell signaling. The hope is that, by using this combination, more than one pathogenic pathway will be silenced simultaneously.

 

One of the investigational drugs that I am very excited about is low-dose IL-2. Approximately 10 years ago, we developed a way to deliver low-dose IL-2 to mice, and we were able to suppress a number of pathogenic pathways, as well as clinical disease, in these mice. Low-dose IL-2 works by expanding regulatory T cells, which are deficient in patients with SLE, and suppressing T follicular helper cells, IL-17 production, and double-negative T cells. So, with low-dose IL-2, you instantly target 4 immune pathways, which probably means that more patients with SLE may have a beneficial effect.

 

Studies of low-dose IL-2 were picked up by investigators in China and by David Klatzmann, MD, PhD, in Paris, with whom I work. Initially, investigators in China gave low-dose IL-2 to patients with SLE and claimed that it was a panacea, with their last report claiming that low-dose IL-2 had an effect in 60% of patients with SLE. They also reported that it expanded cytotoxic T cells and decreased the rate of infections. Dr Klatzmann’s group conducted a multicenter, double-blind, randomized, placebo-controlled trial of low-dose IL-2 that showed a clinical effect in SLE. The study linked that clinical effect to the expansion of regulatory T cells.

 

Another investigational approach is CAR T-cell therapy. To perform CAR T-cell therapy for patients with SLE, T cells are removed from the patient and are then transfected with a T-cell receptor that recognizes one of the surface molecules of B cells, such as CD19, CD20, or BCMA. Patients undergo lymphodepletion, and the transfected T cells are reinfused back into the patient, where they can expand and target the antigen that is recognized by the CAR T receptor.

 

A systematic review of CAR T-cell therapy in rheumatologic autoimmune disorders, including SLE, was presented at CCR East 2024 by Fizza Zulfiqar, MD. In addition to acknowledging promising results from CAR T-cell therapy, Dr Zulfiqar highlighted that long-term follow-up and prospective clinical trials are needed to establish the optimal timing and assessment of the safety and efficacy of CAR T-cell therapy. I am excited about this, but, simultaneously, a lot of things still need to be figured out. New approaches to developing CAR T cells are already being developed, and, in a few years, the landscape of clinical trials of CAR T cells will be completely different from how we think about them now. This is where the excitement is, but I think that the road ahead of us is still quite long.