Organ damage can affect approximately half of all patients with systemic lupus erythematosus (SLE) within a decade of diagnosis, despite disease control. During her presentation at the recent 2025 Congress of Clinical Rheumatology (CCR) East, Michelle Petri, MD, MPH, presented data updating our understanding of organ damage in SLE and potential strategies for prevention and treatment.

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

In SLE, the disease itself and treatment-related effects can lead to organ damage. I want to use cardiovascular (CV) events as an example because CV events in SLE are driven not only by traditional risk factors such as hypertension but also by active SLE and then, unfortunately, prednisone. This is a real example of multifactorial causality of organ damage.

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I made the point during my presentation at CCR East 2025 that the frequency of CV events first peaks in the first 2 years after an SLE diagnosis. People think that organ damage is something that should happen late in the course of SLE, but this is an example of exactly the opposite. So, we need to aggressively treat SLE activity at the very beginning. The problem is that when people are first diagnosed with SLE, they tend to be on higher doses of prednisone. The take-home point that I made during my talk at this year’s meeting was that this is not acceptable. If we are going to reduce these initial CV events, we have to treat active SLE but with much less prednisone.

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The musculoskeletal system is the system that is most commonly impacted by damage in SLE, and that is predominantly osteoporotic fractures mediated by the use of prednisone. Other systems that are commonly involved in organ damage are the renal and neurologic systems, and that is mostly strokes. In general, with the exception of CV events, these types of damage typically occur later after diagnosis.

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We really like to use the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index to monitor organ damage because it is easy to use. Organ damage is either present or absent. However, the most important thing that is taught about organ damage in SLE is that it is biblical. By that, I am referring to the Old Testament chapters—the begats. Once you have organ damage, that begets more organ damage. Organ damage is one of the major drivers of early mortality in SLE, so we would like to prevent even that first event from happening. That is why it is important to treat active SLE aggressively without depending on prednisone.

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It has been reported by Gladman and colleagues that prednisone is directly or indirectly responsible for up to 80% of the organ damage in people with SLE 15 years after diagnosis. So, we want to quickly introduce oral immunosuppression and/or biologics if a patient is on more than 5 mg of prednisone. That is another key finding from the European Alliance of Associations for Rheumatology (EULAR) 2023 guidelines, which I discussed during my presentation at CCR East 2025. In 2023, the target prednisone dose became 5 mg or less, down from 7.5 mg in the 2019 guidelines. However, I do not want my patients to think that even 5 mg is completely safe—it is not. In our study, even 5 mg of prednisone led to an increase in permanent organ damage, although it was much better than the risk at higher doses.

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At this year’s CCR East meeting, I discussed how to translate this in a way that a clinician could easily use in the clinic when the patient is right in front of them. If you increase the patient’s oral prednisone dose by 1 mg and multiply it by 3, that is how much their risk of later organ damage is increased. So, 1 mg is a 3% increase in later organ damage, 5 mg is a 15% increase, and 10 mg is a 30% increase. I think that every physician in that audience would agree that a 30% increase in later organ damage would make them feel uncomfortable.

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During that same presentation, I also talked about vitamin D. A message that I reported some time ago was that if vitamin D supplementation is given to a patient with proteinuria, their proteinuria can improve up to a 25-hydroxyvitamin D level of 40 ng/mL. There is no reason to get higher than 40 ng/mL.

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I presented new data during my talk at CCR East 2025 that were published recently on our work on vitamin D in pregnancy. Pregnant women with SLE have a very high risk of adverse pregnancy outcomes, including outcomes such as miscarriage and preterm birth. We showed a U-shaped curve for vitamin D in pregnancy. Low levels were associated with increased adverse pregnancy outcomes—but so were high levels. And so, there is a “sweet spot.” We want the 25-hydroxyvitamin D level to be between 40 and 59 ng/mL during pregnancy. This differs from the advice on vitamin D that is given to the general pregnancy population, where obstetricians supplement vitamin D like it is one-dose-fits-all. That is not going to work in SLE. The rheumatologist will have to check the patient’s level every trimester to fine-tune it and to make sure that it stays between 40 and 59 ng/mL. This, of course, makes it more complicated, but for a good cause: a successful pregnancy.