Rob Volansky , 2025-05-20 09:30:00
Current treatment paradigms for lupus nephritis offer significant room for improvement, according to a presenter at the Biologic Therapies Summit.
“Everything you think about lupus nephritis may be wrong,” Michelle Petri, MD, MPH, director of the Hopkins Lupus Center and professor of medicine at Johns Hopkins University, told attendees.
As her first example, Petri cited the threshold of 500 mg of protein in the urine as an acceptable benchmark for improvement.
“This is the definition of a complete renal response in randomized controlled trials,” she said. “I call it an incomplete renal response. No one thinks 500 mg is normal.”
According to Petri, clinicians and researchers alike remain uncertain about the nature of damage from conditions such as proteinuria and microalbuminuria resulting from lupus nephritis.
“We do not know how much damage in lupus is from disease activity or accrued damage or both,” she said.
Rheumatologists should additionally be aware that all cases of lupus nephritis are chronic kidney disease, according to Petri.
“By the time we pick up the proteinuria, the patient has already lost one-third of her podocytes and nephrons,” she said. “Our goal should be to stop renal flares because our patients march to dialysis with one renal flare after another.”
Regarding treatment decision-making in lupus nephritis, complications and unmet needs abound, Petri said.
“We know that belimumab (Benlysta, GlaxoSmithKline) protects the epidermal growth receptor factor starting at week 20,” she said.
However, patients often stop taking medications after a few weeks due to “unpleasant gastrointestinal side effects,” thereby limiting the long-term benefits, she added.
“We have to get the patient on board at the first visit,” Petri said. “Treating lupus nephritis is a numbers game.”
Another concern surrounding lupus nephritis treatment pertains to occasional pain medication use or proton pump inhibitors to manage stomach acid. Both of these medications can impact renal complications, according to Petri.
“No NSAIDs, no PPIs,” she said. “You have to preach the low salt, no animal protein diet.”
Although chimeric antigen receptor T-cell therapy has made headlines around the world and across specialties — but particularly in lupus — Petri said she hopes to see more data to validate its efficacy in lupus nephritis.
“If there was a way to give patients cell therapy and achieve a complete remission, I will sign on the dotted line,” she said. “But it is never easy, is it? None of these companies are doing end-of-treatment biopsies.”
This highlights another way that clinicians are “getting it wrong” about lupus nephritis, according to Petri. Although early intervention with some combination of therapies like mycophenolate, belimumab, voclosporin and a drug in the calcineurin inhibitor class can lead to positive outcomes, she said that an end-of-treatment biopsy is really the only way to determine exactly how effective the regimen has been.
“You do a biopsy before you taper,” Petri said.
The final issue Petri raised pertains to the timing of therapy.
“Chronicity is the major predictor of end-stage kidney disease,” she said.
According to Petri, treatment with mycophenolate plus belimumab and a calcineurin inhibitor within the first 10 months of disease onset is the key to preventing long-term damage.
“You have to get more therapies on board from the very beginning if you are going to prevent chronicity,” she said. “We have to do better.”
Sources/Disclosures
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Source:
Disclosures:
Petri M. Emerging Treatments in Lupus Nephritis. Presented at: Biologic Therapies Summit XI; May 9-10, 2025 (hybrid meeting). Petri reports consulting fees from Amgen, AnaptysBio, Annexon Bio, Arthros-FocusMedEd, AstraZeneca, Atara Biosciences, Aurinia, Autolus, Biocryst, Biogen, Boxer Capital, Cabaletta Bio, Caribou Biosciences, CTI Clinical Trial and Consulting Services, CVS Health, Escient Pharmaceuticals, Emergent Biosolutions, Exo Therapeutics, Gentibio, GlaxoSmithKline, iCell Gene Therapeutics, IQVIA, Idorsia Pharmaceuticals, Eli Lilly, Merck EMD Serono, Nexstone Immunology, Nimbus Lakshmi, Novartis, PPD Development, Proviant, Regeneron, Sanofi, Seismic Therapeutic, Senti Biosciences, Sinomab Biosciences, Takeda, Tenet Medicines, TG Therapeutics, UCB, Worldwide Clinical Trials and Zydus; as well as grant support from AstraZeneca, Aurinia, Eli Lilly, Exagen, GlaxoSmithKline and Janssen.
