THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



New biomarkers, new drugs show promise for improving lupus nephritis outcomes

Chaim Putterman, MD
Chaim Putterman, MD

The future of lupus nephritis is in new biomarkers and therapies for the disease, and a panel of three experts will detail that future during Lupus Nephritis: New Decade, New Approaches.

This ACR Convergence 2020 session will have its first viewing, including a live question-and-answer period, from 5 – 6 p.m. EST Sunday, Nov. 8. Registered attendees will also have on-demand online video access to watch a replay through Wednesday, March 11.

Chaim Putterman, MD, professor of medicine and microbiology & immunology, Albert Einstein College of Medicine, and Associate Dean for Research at the Azrieli School of Medicine of Bar-Ilan University, will open the session with a look at recent progress in biomarkers, such as their use in early diagnosis and prediction of disease flare, and his predictions for more rapid integration of novel biomarkers into clinical care.

Clinicians treating lupus patients have been using serum anti-double-stranded DNA antibodies and C3 and C4 complement levels for decades, and new biomarkers have yet to supplant these tried and true indicators. Across different studies and different patient cohorts, no new potential biomarker has yet been shown to consistently do better than traditional biomarkers.

“Continuing to use these readily available serological tests alone in routine clinical practice would be fine if the performance and predictive ability of these biomarkers would be perfect, but unfortunately that is not the case,” said Dr. Putterman, underscoring the need to continue to look for additional biomarkers to provide information traditional biomarkers don’t.

Biomarkers have the potential to turn that tide through earlier identification of need for intervention, earlier identification and follow-up of specific organ involvement, better measuring of disease activity, and increased ability to predict disease severity.

“Omics” approaches are harnessing new technologies to improve the performance of biomarkers.

“Instead of focusing on an individual molecule, we are profiling many analytes simultaneously,” Dr. Putterman said. “If you look at five or six or seven markers at a time, those perform much better than just a single mediator. Indeed, omics approaches have allowed a much more comprehensive, big-data, non-biased look at disease in the patients that have the outcome of interest versus those that don’t.”

Whether proteomics, genomics, or transcriptomics, approaches incorporating multiple analytes at the same time provide a more detailed and accurate snapshot of the mechanisms operative in driving the nephritic process.  

Joan T. Merrill, MD
Joan T. Merrill, MD

Joan T. Merrill, MD, director of clinical projects, Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation, will highlight new therapies for lupus nephritis and data from the latest trial results. 

“There’s some data that the faster you can get people to a certain stage of improvement, the better their outcome is,” she said. “Maybe we can start to use recent insights into how nephritis works to get closer to that goal.” 

Dr. Merrill will review the pharmaceutical agents with recent promising results for lupus nephritis, including the anti-CD20 drug obinutuzumab, the calcineurin inhibitor voclosporin and the BLyS antagonist belimumab.

In the past year, results from several lupus nephritis trials have been made public.

“Three in a row have been pretty favorable, so it looks like we’ve finally learned how to do lupus nephritis trials,” said Dr. Merrill. “One of the things that has happened is that people are tapering the steroids a lot faster than we used to do, so you can see the difference between treatment and placebo sooner.” 

Calcineuirn inhibitors have many side effects. The drug tacrolimus is in use for nephritis and is safe if used carefully, but there is still some incidence of diabetes and high blood pressure, and potential for kidney damage, she said. Some data suggests that voclosporin may be a safer alternative. 

“Voclosporin is actually almost identical to the more problematic cyclosporine, but one little tweak from its structure and it’s more potent and handled more efficiently by the body. At least in some other diseases there’s data to suggest that it might be safer,” she said. “It’s been tested now in lupus nephritis. It did very well in a phase 2 trial and just this year it was found to be efficacious in a phase 3 trial.”

Brad Rovin, MD, director, Division of Nephrology Vice Chair of Research, Internal Medicine, Ohio State University Wexner Medical Center, will outline the current standard of care and role of for repeat biopsy for lupus nephritis patients.