Systemic Lupus Erythematosus: Response to Treatment With Newer Therapies
As seen at the 2023 Congress of Clinical Rheumatology (CCR) East, the treatment of systemic lupus erythematosus (SLE) continues to evolve, with newer therapies such as anifrolumab, voclosporin, and belimumab now under consideration in various settings.
Following the conference, featured expert Vasileios C. Kyttaris, MD, was interviewed by Christopher Ontiveros, PhD. Clinical perspectives from Dr Kyttaris are presented here.
Vasileios C. Kyttaris, MD
Assistant Professor of Medicine
“There is a great deal of interest right now in learning how best to incorporate newer treatments for lupus nephritis into our treatment paradigm. We are also interested in determining how newer medications for SLE can help decrease our reliance on corticosteroids, especially the chronic use of corticosteroids for the prevention of flares.”
The 2 main goals in the treatment of SLE are to prevent flares with the use of background medications (eg, hydroxychloroquine) and to treat acute flares with the use of more effective medications (ie, biologics, immunosuppressives, and corticosteroids). We treat flares differently, depending on whether they are arthritis related, nephritis related, or skin related, among other factors. For example, we may use methotrexate for arthritis flares, but we would use mycophenolate or cyclophosphamide for nephritis flares. I think that finding a medication that works for the treatment of all types of flares and is also effective for the prevention of flares would be the holy grail in SLE.
There is a great deal of interest right now in learning how best to incorporate newer treatments for lupus nephritis into our treatment paradigm. We are also interested in determining how newer medications for SLE can help decrease our reliance on corticosteroids, especially the chronic use of corticosteroids for the prevention of flares.
Cyclophosphamide had been a mainstay of treatment for renal SLE in the past, but we are using less and less of it today, and, instead, mycophenolate mofetil has become the standard of care for the treatment of renal SLE. Belimumab and voclosporin can each be combined with standard therapy mycophenolate to treat acute renal flares. In addition, belimumab may also prevent future renal flares, while voclosporin may help limit total corticosteroid use during the treatment of acute lupus nephritis. We still have to determine, however, when belimumab and/or voclosporin should be initiated and how long patients should remain on combination therapy.
In just the last year and a half, we have also added anifrolumab for nonrenal SLE to the treatment armamentarium. Anifrolumab inhibits type I interferon signaling, has been shown to be effective for the treatment of skin disease, and is approved by the US Food and Drug Administration for patients with moderate to severe SLE who are receiving standard therapy. An interesting observation with anifrolumab is that the treatment effect seems to be present quite early. In fact, you can have a clinical effect as early as 8 weeks, and this could have a role in the earlier tapering of corticosteroids. In contrast, with belimumab, you may wait for 6 or 7 months to determine whether it is effective before deciding to move on.
For nonrenal SLE, we are still not using the biologics anifrolumab and belimumab in the first-line setting. For the most part, these agents are used in patients who have failed hydroxychloroquine and at least 1 immunosuppressive agent. Real-world data presented at CCR East by Bell et al suggested that belimumab might have a steroid-sparing effect, but this was not a randomized trial. Other data suggest that anifrolumab may also decrease the cumulative corticosteroid exposure in patients with lupus. I think that both drugs have some evidence that they may help limit the role of steroids, or at least decrease the cumulative corticosteroid exposure, in their respective settings.
Of course, optimizing the use of hydroxychloroquine in SLE also continues to be of interest. Michelle Petri, MD, MPH, touched on the issue of long-term hydroxychloroquine therapy at CCR East. She is a strong advocate for the use of hydroxychloroquine as a background therapy for virtually every patient with lupus, and she presented some data showing that hydroxychloroquine can avert death, prevent thrombosis, and improve the effectiveness of mycophenolate in lupus nephritis.
Nonetheless, hydroxychloroquine is associated with retinal toxicity, especially in patients who have been taking the drug for decades. Because of this, the current recommendation that is backed by the American Academy of Ophthalmology and the American College of Rheumatology is not to use more than 5 mg/kg daily on a chronic basis in order to avoid irreversible visual disturbance or even visual loss. At this point, hydroxychloroquine remains the backbone of therapy for lupus, but that has to be weighed against its potential for toxicity, especially after use for more than a decade.
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