Insights into SLE & Lupus Nephritis From the 2025 Review Course

CHICAGO—Each year, the ACR provides a tremendous service to the rheumatology community by organizing its annual Review Course sessions at ACR Convergence. Not only are the subjects selected for these sessions consistently timely and relevant, but also the speakers who present the material are invariably skilled at distilling complex topics down to their essence. This makes for talks that are engaging, high yield and always popular among conference attendees.

Systemic Lupus Erythematosus

The first lecture this year was given by Stacy Ardoin, MD, division chief of pediatric rheumatology, Nationwide Children’s Hospital and The Ohio State University, Columbus, and its focus was on both pediatric and adult systemic lupus erythematosus (SLE).

Dr. Ardoin began by laying out several goals that all clinicians should have when caring for patients with SLE, namely: 1) controlling disease activity, 2) preventing organ damage, 3) improving patients’ quality of life, and 4) minimizing side effects from therapy.

At the moment, only one medication—belimumab—is approved for pediatric SLE by the U.S. Food & Drug Administration (FDA), but Dr. Ardoin explained that pediatric rheumatologists often employ a range of therapies that, although off label, are still found to be helpful in managing patients’ disease. Without question, hydroxychloroquine is indicated for every pediatric and adult patient with SLE unless an absolute contraindication to its use exists or if a patient has significant side effects with the medication; in the latter case, Dr. Ardoin recommended trying a lower dose of the medication or using chloroquine in its place.

Similar to other rheumatic conditions, SLE can now be managed using a treat-to-target approach, with the target being either remission or low disease activity state. In the past, Dr. Ardoin explained, such targets would have been aspirational, but in recent years they have become realistic thanks to better treatments and a better understanding of how to use these targets. The Lupus Low Disease Activity State is characterized by the absence of activity in major organ systems, a prednisone dose of no more than 7.5 mg per day and standard maintenance doses of immunosuppressive treatments.¹

Successful Treatment of Lupus Nephritis

Specific ways to measure success in treating lupus nephritis include improvement in glomerular filtration rate (GFR) and proteinuria, and Dr. Ardoin cited the guideline published by the ACR in 2024 as a particularly helpful resource for clinicians.² Significant innovations from these guidelines were the concept of using triple therapy at time of diagnosis of lupus nephritis and using such factors as the Inter­national Society of Nephrology/Renal Pathology Society (ISN/RPS) class of nephritis, GFR, degree of proteinuria and presence or absence of significant hypertension to guide selection of therapy.

She noted the FDA’s approval of obinutuzumab for the treatment of adults with active lupus nephritis came after publication of these recommendations, thus updates may be needed with respect to this medica­tion; recommendations from the European Alliance of Associ­ations for Rheumatology, however, do include obinutuzumab.³

Non-Renal Manifestations

For non-renal manifestations of disease, Dr. Ardoin explained that this is a bit of the Wild West in that more variability in practice patterns exists even among experts in the field, although this should improve with the publication of the guideline for the management of SLE presented at this year’s ACR Convergence.

When a patient has possible neuro­psychiatric lupus (NPSLE), Dr. Ardoin noted that it is important to first ask a few questions: Could this be something else, like infection, malignancy or a toxic exposure? Why is the patient flaring now, and is it related to medication adherence? Is the patient pregnant or planning to become pregnant? If NPSLE does appear to be the correct diagnosis, then the clinician must consider if the driving issue is ischemia, in which case anticoagulation is important, or inflammation, which would require consideration of glucocorticoids, cyclophosphamide and anti-CD20-directed therapies.

Symptomatic treatments, such as antipsychotics and antidepressants, may also have a role to play, and Dr. Ardoin recommended shared decision making with patients around treatment strategies whenever this is possible.

For patients with cutaneous disease, Dr. Ardoin stressed the importance of checking for medication adherence, the use of topical therapies and photoprotection, and highly encouraging patients who smoke to quit because this may dramaticly improve their skin disease. Options for medical management include dapsone, quinacrine, anifrolumab, anti-CD20 therapy and lenalidomide.

For articular disease, Dr. Ardoin has had more success with methotrexate and leflunomide than with mycophenolate mofetil and azathioprine, and she sometimes borrows from treatment strategies for juvenile idiopathic arthritis and rheumatoid arthritis (RA) in considering treatment with tocilizumab, abatacept or Janus kinase inhibitors, although the latter may have concerns in patients with risk factors for thrombotic or cardiovascular disease.

Dr. Ardoin noted considerations that are particular to pediatric vs. adult patients with SLE that clinicians must keep in mind. Pediatric patients often present with more severe disease and may have monogenic forms of lupus, such as that seen with C1q deficiency, and given their earlier age of onset they have more potential years to be exposed to the effects of high disease activity or to incur the effects of years of drug exposure. Adults, meanwhile, often have more comorbidities and, thus, a greater degree of polypharmacy. Both pediatric and adult patients may face challenges with medication adherence, social impacts on their families, struggles with mental health, absences from work or school and impacts on their reproductive health/family planning.

Dr. Ardoin also discussed the situation in which a patient’s laboratory studies and physical exam look good, but they feel poorly. In such cases, she recommended that the rheumatologist consider different etiologies of the patient’s not feeling well, including medication side effects, fibromyalgia/amplified musculoskeletal pain syndrome, depression, adrenal insufficiency, other medical conditions that may arise secondary to the effects of SLE and life stressors.

Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

1. Franklyn K, Lau CS, Navarra SV, et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615–1621.
2. Sammaritano LR Askanase A, Bermas, BL, et al. 2024 American College of Rheumatology (ACR) guideline for the screening, treatment, and management of lupus nephritis. https://rheumatology.org/lupus-guideline.
3. Fanouriakis A, Kostopoulou M, Anders H_J, et al. EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update. Ann Rheum Dis. 2025 Oct 16:S0003-4967(25)04412-7. Online ahead of print.

Reprinted and adapted from an article on The Rheumatologist’s website, https://www.the-rheumatologist.org/article/reflections-on-b-cells-in-sle-looking-back-and-looking-ahead.