While treatment advances have improved outcomes for patients with systemic lupus erythematosus (SLE), there are still significant unmet needs, particularly for patients with lupus nephritis (LN) and severe SLE. The field is hopeful that these unmet needs will be addressed by the current and future treatment advances. At the recent 2024 Congress of Clinical Rheumatology (CCR) West, several talks and presentations focused on unmet needs in the treatment of SLE.

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

Some of the biggest unmet needs in SLE are determining how to prevent LN, how to quench neuropsychiatric lupus, and how to prevent the severe life-threatening disease that keeps people in the hospital for long periods. Severe, catastrophic, life-threatening illness has typically been excluded from drug development. As we are getting a little more comfortable in our ability to treat moderate to severe SLE, we are now looking at trying to treat severe disease, put people in remission, improve quality of life, and prevent damage. These and other unmet needs were discussed during a presentation by Richard A. Furie, MD, at CCR West 2024.

We have long relied on steroids as our first step to quench and treat disease activity. We now understand that the price of treating disease activity with steroids is very high. As we have more therapeutic options and targeted therapies, we are now able to focus on decreasing the use of steroids for not only acute and chronic moderate to severe disease but also for acute, severe, life-threatening illness.

A poster presented at CCR West 2024 by Dr Furie and colleagues reported the rate of steroid reduction and withdrawal in a post hoc analysis of the long-term extension studies of the phase 3 TULIP-1 and TULIP-2 anifrolumab trials. Based on the European Alliance of Associations for Rheumatology (EULAR) recommendations, the treatment goal is to taper the dose of steroids to 5 mg/day or less, but, ideally, all of our patients should be completely off steroids. At week 208, higher proportions of anifrolumab-treated patients vs placebo-treated patients had tapered glucocorticoids from 7.5 mg/day or higher to 5 mg/day or lower (58.2% [39 of 67 patients] vs 47.8% [11 of 23 patients], respectively) or had withdrawn from glucocorticoid therapy (22.4% [15 of 67 patients] vs 8.7% [2 of 23 patients], respectively).

Another poster from CCR West 2024 reported on the clinical characteristics of patients with SLE with and without LN. Patients with LN had a higher incidence of comorbidities compared with patients without LN. These data make a lot of sense in terms of the comorbidities and the associated complexity of severe SLE and LN. We are acknowledging more and more that people with severe LN develop heart failure, which is likely related to ischemic heart disease, but lupus cardiomyopathy should be considered in the differential diagnosis. Furthermore, while diabetes and hypertension are known complications of steroid use and LN, the authors unexpectedly reported an increase in chronic obstructive pulmonary disease in patients with LN.

Finally, I think that the SLE field has become wiser about designing clinical trials and the choice of therapies that advance to late-stage development. Better clinical trial design has propelled us to this next level. We have had several successful drug development programs in SLE and LN in the last few years, and CAR T-cell therapy brings forth the possibility of long-term, drug-free remission and cure. The big excitement surrounding the CAR T-cell therapy data, some of which were discussed in a talk by Georg Schett, MD, at CCR West 2024, is the promise of SLE remission without drugs.