Targeted therapies are the most recent additions to the treatment armamentarium for systemic lupus erythematosus (SLE) and are providing patients with improved outcomes. Researchers and clinicians at the 2025 Congress of Clinical Rheumatology (CCR) East presented data from various studies aiming to highlight the role of targeted therapies in the treatment of patients with SLE.

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Following these presentations, featured expert Michelle Petri, MD, MPH, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Dr Petri’s clinical perspectives on these findings are presented here.

The oral immunosuppressive drugs mycophenolate mofetil and azathioprine are broadly immunosuppressive. However, perhaps our broadest immunosuppressive therapy for SLE is prednisone, as nearly all aspects of the immune system are downregulated by prednisone. In addition to rituximab, which we use off-label for SLE, our currently available biologic targeted therapies for this disease include the following 2 other monoclonal antibodies (mAbs): belimumab and anifrolumab-fnia. Belimumab targets BAFF/BLyS, a B-cell survival factor, and was US Food and Drug Administration (FDA) approved for SLE in 2011. More recently, it was approved for renal lupus in 2020. Anifrolumab-fnia is an anti-interferon (IFN) receptor mAb that was FDA approved for SLE in 2021.

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Knowing a targeted therapy’s mechanism of action can be helpful because we try to match the mechanism of action to the appropriate patient. For example, we know that belimumab works the best for nonrenal SLE in patients who have low levels of complement or anti–double-stranded DNA antibodies, which are markers that the B-cell pathway is involved in the pathogenesis of their SLE. For anifrolumab-fnia, because it targets the IFN gene signature, we would like to prioritize it for patients whose disease is driven by IFN. That is likely the case for most of our patients who have cutaneous lupus. However, anifrolumab-fnia is only FDA approved for SLE and is not approved for patients who have chronic cutaneous lupus alone, without SLE.

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Anifrolumab-fnia works very quickly. In fact, patients may experience some improvement within the first month. If there is not any improvement in 3 months of treatment with anifrolumab-fnia, I would probably stop this therapy and move on to something else. Luckily, anifrolumab-fnia works for the majority of patients with cutaneous lupus in whom it is started. For belimumab, the BAFF/BLyS pathway is a little strange. There is improvement in complement and in anti–double-stranded DNA antibodies even by the first month. However, clinical improvement takes time to reach maximal impact. Some patients will not plateau or achieve their maximum benefit until about 6 months following the start of treatment. For belimumab, I think that it is important for both the patient and the physician to be patient during those 6 months of treatment. Whereas, for anifrolumab-fnia, I think that a decision of either yes, it is working, or no, it is not working, can be made by around the third month of treatment.

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It is worth mentioning that a significant proportion of patients on targeted therapies are able to achieve remission. At CCR East 2025, a poster presented by Aarat M. Patel, MD, showed that approximately 14% to 28% of patients started on belimumab achieved remission in 1 year. Remission has also been shown in patients on anifrolumab-fnia. After patients had finished 1 year of the randomized TULIP-1/TULIP-2 trials, anifrolumab-fnia developers did not break the blind, and this was unique. They continued to have patients on placebo throughout a 3-year long-term extension trial. This allowed them to show that the remission is durable, and, in fact, the frequency even increases over time as compared with an ongoing placebo group. We have never talked about remission in patients on our oral immunosuppressive drugs because, while we usually improve disease activity, we do not squash it enough to put a lot of people in remission. So, the fact that we are able to use the word “remission” now shows how much better the results are with targeted therapy.

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Regarding targeted therapies, I discussed CAR T cells during my presentation, “Ten Things I Want You to Know About Lupus,” at this year’s CCR East meeting because, with CAR T-cell therapy, this is the first time people have talked about the possibility of treatment-free remission or possibly even a cure. The initial work on CAR T cells in SLE was done by Georg Schett, MD, and colleagues in Erlangen, Germany. Of their first 8 patients, all seemed to go into remission. One patient has been in remission for almost 5 years, and all of them got off treatment. However, more recent results have not been as easy to understand, especially for some of the companies that have released their data to the public. For example, the urine protein did not go down to 0 in everyone. Unless an end-of-treatment biopsy is performed, simply having unresolved proteinuria does not tell the clinician how much of it is due to insufficiently treated disease activity in the kidney vs chronic scarring. I think that there is going to be a lot more needed to dissect what is going on in these CAR T-cell trials.

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The other presentation that I gave at CCR East 2025 was on lupus nephritis. I tried to emphasize that our current measure, the urine protein to creatinine ratio (UPCR), does not tell us how much of that protein is from active disease needing more treatment vs chronic damage or scarring. This means that we do not know if it is correct to say whether, at 1 year, the patient has or has not met a complete renal response (≤500 mg/g). I emphasized work that has been done by Ana Malvar, a nephrologist from Argentina. She has pioneered end-of-treatment biopsies, so that we actually know whose lupus nephritis is adequately treated. There needs to be more attention focused on end-of-treatment biopsies, rather than guessing that a low UPCR must be good and that a moderate or high UPCR must be bad. We really need to know for sure who still has active renal lupus.