The systemic lupus erythematosus (SLE) treatment pipeline includes therapies that target different mechanisms of the disease. Drawing on presentations from the RhAPP Seventh Annual National Conference 2026, Danielle Gatti-Palumbo, PharmD, BCACP, reviews selected clinical trial findings and considers how emerging therapies may help individualize treatment for SLE.

Following these presentations, featured expert Danielle Gatti-Palumbo, PharmD, BCACP, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Gatti-Palumbo on these findings are presented here.

Coming out of RhAPP 2026, a key takeaway was the importance of looking at the newer agents and recognizing that SLE treatment is not one size fits all. Even if a patient’s skin manifestations are well controlled, they may eventually develop kidney involvement. This means that looking at the different domains and the pathogenesis of SLE itself is critical. The patient’s disease may appear to be well controlled on one medication, but SLE may still be active, and we may ultimately end up having to switch to another agent.

The plenary presentation at RhAPP 2026 titled “Emerging Therapies in SLE: What’s Next in Clinical Care?” given by Jeannette Hart, PA-C, focused on litifilimab, subcutaneous anifrolumab, deucravacitinib, dapirolizumab pegol, obinutuzumab, ianalumab, and upadacitinib. These drugs directly or indirectly modulate type I interferon, which we know is a key driver of inflammation in SLE, especially in patients with skin manifestations. An example of research targeting type I interferon signaling is part A of the phase 2/3 AMETHYST trial of litifilimab in cutaneous lupus erythematosus, which showed an improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) scores.

In SLE, we know that there is also B-cell dysfunction and a loss of tolerance to multiple cell antigens. B cells drive the inflammation and cytokine release seen in SLE. Obinutuzumab has been engineered for the effective depletion of CD20+ B cells. Ianalumab may serve as another potentially useful B-cell depleter.

Dapirolizumab pegol, which inhibits CD40L, is a pegylated biologic and lacks an Fc domain. This design addresses concerns about the platelet activation and thrombosis that were associated with earlier anti-CD40L antibodies. The phase 3 PHOENYCS GO trial showed improved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responses at week 48 with dapirolizumab pegol, with supportive Systemic Lupus Erythematosus Responder Index 4 (SRI-4) findings. PHOENYCS FLY, a second pivotal, confirmatory phase 3, registrational trial of dapirolizumab pegol in patients with moderate to severe active SLE, is ongoing.

The plenary presentation at RhAPP 2026 titled “Year in Review With Q&A” given by Jessica Farrell, PharmD, and Audrey Gibson, PA-C, discussed nipocalimab, which represents a potential first-in-class breakthrough for SLE. It selectively blocks the neonatal Fc receptor, reducing circulating pathogenic IgG antibodies and immune complexes. In the phase 2 JASMINE-SLE trial, nipocalimab achieved the primary end point of SRI-4 response at week 24. In the week 52 subgroup analysis, the autoantibody-positive group had an even better treatment effect.

Also at RhAPP 2026, a masterclass on CAR T-cell therapy presented by Leonard Calabrese, DO, Betsy Kirchner, DNP, Philip Mease, MD, and Christy Vath, PA-C, covered the history of CAR T-cell therapy and touched on its role in treating SLE. The presenters discussed how CAR T-cell therapy is not a one-size-fits-all treatment. Not everybody responds the same way, and even in vivo complete B-cell depletion may not correlate with clinical response. Moreover, CAR T-cell therapy requires a lot of time and resources, along with extensive patient preparation. Its safety profile also warrants caution, so we may use it only in the most severe cases of SLE. In short, we still have much to learn about CAR T-cell therapy and its potential as a treatment for SLE.

Finally, without head-to-head comparisons, we cannot necessarily say that one of these drugs yields a better treatment response than another. However, having multiple treatment options may be helpful because if a patient is not responding optimally to one drug, switching to a different drug with a different mechanism of action may be beneficial.

Ultimately, treatment selection will depend on the severity of the SLE and the pathway driving the disease, which we may or may not know. Currently, it depends on the patient’s clinical phenotype. Are there predominantly joint manifestations, like what we typically see in SLE? Or are there predominantly skin manifestations, for which we would consider treating with anifrolumab? Is there kidney involvement, for which we would perhaps use obinutuzumab instead? I think that we still have many drug targets and mechanisms to explore, but it is an exciting time because so many investigations are underway across many different SLE therapies.