<p>Systemic lupus erythematosus (SLE) is a highly variable and heterogeneous disease. Accordingly, a one-treatment-fits-all approach is not practical for the management of SLE, and a personalized and/or precision-based approach to treatment warrants consideration. Studies related to this important emerging concept were presented at the <strong>2024 Congress of Clinical Rheumatology (CCR) East</strong>.</p> <p> </p> <p><em>Following these proceedings, featured expert George C. Tsokos, MD, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Tsokos are presented here.</em></p>

Personalized medicine can be described as a situation in which a clinician sees a patient in the office who has a specific disease, and they try to tailor treatment to address what that patient needs. For example, if a patient with SLE is in the office for skin disease, and the rest of their organs are not particularly active with disease, then the clinician can use certain drugs that we know have a better chance of treating skin disease. Steroids may help, and anifrolumab-fnia may help even more. Similarly, if a patient presents with active kidney disease, then the clinician must think about treatments that suppress inflammation.

 

Precision medicine goes a step beyond personalized medicine, and to use this approach we need to know the exact mechanisms that are involved in the development of the disease. Lupus is a very heterogeneous disease at the pathogenetic level, which means that not all patients share the same pathways for their disease. For example, for patients in whom IFN signaling is important in the process of their lupus, a TYK2 inhibitor or anifrolumab-fnia may have a very good effect since they can suppress IFN signaling. Similarly, if you were to isolate the people who have BAFF signaling that is dominant in the pathogenesis of their disease, then these individuals may respond better to the BAFF inhibitor belimumab. This is precision medicine. Unfortunately, many of the available biologics are used without considering what exactly is going on in the patient.

 

There are other important considerations in precision treatment, especially for patients with lupus. For example, IFN signaling is required for the expansion and development of regulatory T cells, which are compromised in patients with lupus. If we shut down IFN signaling, we expect to see beneficial effects. But, simultaneously, you have to consider other potential deleterious effects that could occur due to reduced IFN signaling and may be responsible for not seeing a better effect in more patients.

 

Wu et al presented a study at CCR East 2024 related to this topic in which investigators developed an IFN 5-gene signature score to identify patient subsets and for use as a potential biomarker for deucravacitinib. There were also other useful clinical studies presented at CCR East 2024 that tried to identify the patients who would respond better to various treatments than others. However, these studies do not address personalized medicine the way that I would like them to, and they do not touch precision medicine at all.

 

After the US Food and Drug Administration (FDA) approval of many of these new therapies, investigators often will start collecting information to determine which people can benefit the most from treatment. Hopefully, these post-FDA approval studies that are being performed by these academically oriented clinicians will eventually identify such people. The work that these investigators are doing is certainly very important, as they are trying to refine the use of these FDA-approved drugs. But, at the same time, I have to say that they do not address the core of the problem that we have in lupus management, which is improving our ability to use precision medicine.