Real-world studies complement randomized controlled trials (RCTs), providing additional data from routine clinical practice. At ACR Convergence 2023, researchers analyzed real-world data to shed light on a variety of issues affecting patients with systemic lupus erythematosus (SLE).

Following these presentations, featured expert Maureen A. McMahon, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr McMahon’s clinical perspectives on these studies are presented here.

While RCTs are the gold standard for evaluating the safety and efficacy of new treatments, there are also some limitations. We do not always get a diverse patient population in clinical trials, and so, real-world data may give us the opportunity to capture some of those patients who might not be represented as well in RCTs. Additionally, while clinical trials control for many variables, such as the use of glucocorticoids, they do not necessarily reflect scenarios that might be encountered in real life when things do not quite go according to script. Real-world data can sometimes help to identify health disparities, but they also really give us the opportunity to capture what is going on in routine clinical practice and identify areas that we should focus on to improve patient care overall.

There were several studies presented at ACR Convergence 2023 that involved real-world data. An interesting pragmatic target trial utilizing electronic health records identified a large cohort of patients with incident prescriptions for SGLT2 or DPP4 after a diagnosis with SLE (abstract 1579). They did propensity score matching to make sure that the groups were as matched up as they could be, and they found a lower risk of major adverse cardiovascular events and renal progression with SGLT2 inhibitors in patients with SLE. These preliminary data certainly warrant further investigation to determine if there is a true benefit in our patient population that is similar to what has been seen in other disease populations.

The SPOCS trial was another analysis that took a real-world patient cohort and followed these patients over time to see practice patterns, looking at the interferon (IFN) gene signature (low or high) (abstract 0592). Patients who were followed were not necessarily brand-new SLE patients, they were just patients who were new to this study. One might theorize that patients with a high IFN score might respond differently to an agent that targets IFN than patients with a low IFN score, but we are still trying to understand this biomarker. Of course, the treating providers in SPOCS did not know the baseline IFN signatures of their patients at the time, so this report was really just a reflection of what that IFN score looks like in a real-world patient population—and the practice patterns that are seen in the real world. Overall, a high proportion of patients were taking steroids, with many of them also taking a higher dose (ie, >7.5 mg). The percentage of patients at doses higher than 7.5 mg increased from 26% at the start of the study to more than 45% at 12 months. And, although that percentage decreased over time thereafter, it never reached baseline levels.

Clearly, we want patients to receive the lowest dose of corticosteroids possible so that we are less likely to incur the future damage and side effects that are well known to correlate with the higher doses. While the IFN gene signature is still a biomarker that is in development, these types of studies, along with others, might lead to the commercial availability of such a test in the future. The IFN-high patients did show a higher percentage of patients with glucocorticoid use, even though the mean dose was similar up until the end of the study. They also did show a little bit of a numerically higher use of biologics. These data highlight the potential of additional biomarkers in SLE; ie, perhaps something like the IFN gene signature could be used to identify patients who may have more aggressive disease over time, and maybe these would be the patients we might want to focus on when thinking about newer therapies to avoid excessive glucocorticoid use.

Other abstracts presented at ACR Convergence 2023 focused on SLE-associated comorbidities. For example, the RELESSER-PROS multicenter cohort study highlighted how common depression is in patients with SLE (abstract 1446). An association was found between glucocorticoid use and self-reported depression, which is very important and something that we can use to remind ourselves to decrease glucocorticoid use. Although depression is not one of the most common reasons that we have for decreasing glucocorticoids in patients with SLE, this shows that there may be implications for patient health above and beyond the traditional ways that we think of glucocorticoids causing adverse outcomes.

Cardiovascular disease is also commonly associated with SLE. A study by Parperis and Bhattarai highlighted that patients with SLE are at increased risk for the development of acute coronary syndrome and that, when they have a cardiovascular event, it is associated with longer hospital stays and increased costs compared with those for patients who do not have lupus (abstract 2257). Antiphospholipid syndrome, chronic renal disease, end-stage renal disease, and a history of thromboembolism may be associated with a higher rate of acute coronary syndrome.