<p>Recent data highlighted at <strong>ACR Convergence 2025</strong> underscore how emerging B-cell–directed therapies are reshaping expectations for systemic lupus erythematosus (SLE) control. Established biologics are being reevaluated against modern remission and steroid-sparing goals, while novel cellular and T-cell–directed therapies are allowing the field to consider the possibility of deeper, more durable responses.</p> <p><br></p> <p><em>Following these presentations, featured expert Anca D. Askanase, MD, MPH, was interviewed by</em> Conference Reporter <em>Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Askanase are presented here.</em></p>

It is very clear that SLE is a disease of our antibodies. Accordingly, targeting the cells that make antibodies makes a lot of sense. This concept was first considered soon after the US Food and Drug Administration (FDA) approval of the B-cell–targeting drug rituximab for the treatment of lymphoma in the late 1990s and the introduction of B-cell depletion treatment strategies in hematologic malignancies in the early 2000s. It is on the coattails of these B-cell–targeted therapies that trials in SLE have evolved. Belimumab, a B-cell–targeting treatment, was the first FDA-approved drug for SLE in many decades and has been a big success story as data on efficacy and safety continue to accumulate. In addition, the recent FDA approval of obinutuzumab for lupus nephritis has further improved our understanding of how to design and implement clinical trials in SLE.

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At every ACR Convergence meeting, we learn more about refining some of the earlier study outcomes. At ACR Convergence 2025, my group presented a post hoc analysis of belimumab studies in SLE (poster 1531). We refined the Definition of Remission in SLE (DORIS) and the Lupus Low Disease Activity State (LLDAS) used in earlier SLE studies to exclude the glucocorticoid component from the target definitions because there was no mandated steroid taper at that time as there is now, which resulted in prolonged glucocorticoid courses in many patients. In the post hoc analysis, belimumab attained approximately 2-fold higher rates of non-glucocorticoid-DORIS and non-glucocorticoid-LLDAS than reported with full DORIS and LLDAS definitions. We have come a very long way in our use of corticosteroids and steroid-sparing agents when managing SLE.

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This year at the ACR Convergence meeting, there was an interesting spectrum of studies highlighting the enormous amount of work that is happening in the CAR T-cell arena, including the study presented by Jan K. Davidson-Moncada, PhD, MBBS (poster 1532). CARs are synthetic fusion proteins that redirect the genetically engineered cells to recognize and eliminate target cells. The majority of CAR therapies in development for SLE are autologous; however, there is a lot of interest in developing allogeneic products made from healthy volunteers.

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CAR T-cell therapy is one area that we are just starting to explore. Since the initial publications on CAR T-cell therapy became available, we are now more aware of the spectrum of responses among people with SLE. Based on the available data, it seems that remission is achieved in somewhere around 80% of patients with SLE who are treated with CAR T-cell therapy, which I think is expected given the heterogeneity of SLE pathogenesis.

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Our group had a presentation at ACR Convergence 2025 on a systematic review and analysis of all the CAR T-cell therapy studies published through June 2025 (abstract 2693). We identified 12 studies targeting CD19-targeted CAR, 2 studies targeting bispecific CD19-BCMA CAR T cells, and 2 studies evaluating allogeneic CAR products, which included a total of 98 patients. Thus far, it seems that this therapeutic modality may offer consistent efficacy with an acceptable safety profile. There is excitement from clinicians and investigators, interest from the drug developers, and awareness and engagement from patients to try these new CAR T-cell therapy treatments that have the aura of potential drug-free remission.

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Related, there was also a lot of enthusiasm at this year’s ACR Convergence meeting about T-cell engagers. Investigators from China presented data on a CD3xCD19 T-cell engager, which is a specific antibody that creates an immunologic synapse between the CD3-positive T cells and the C19-expressing B cells, thereby allowing the cytotoxic effect of the T cells to eliminate the CD19-positive B cells (poster 0646). Finally, I was the speaker of a session on T-cell engagers, during which I went through the data in both SLE and other rheumatic diseases and discussed where we think the field is going. As opposed to CAR T-cell therapy, where the doses that are used for malignancies are translated and seem to be efficacious for SLE, there is a little bit of a struggle to identify the precise dose for T-cell engagers for SLE.