Treatment of Lupus Nephritis Continues to See Progress

When obinutuzumab was added to mycophenolate mofetil, more lupus nephritis patients responded than with mycophenolate mofetil alone. Earlier agents targeting anti-CD20 didn’t meet their primary endpoints for lupus nephritis, but obinutuzumab causes greater B cell depletion.

“However, the rapid steroid taper in this trial might also have helped demonstrate the treatment effect,” Dr. Merrill said.²

In pivotal phase 3 trials, voclosporin demonstrated superior efficacy compared to mycophenolate mofetil alone, and belimumab was effective when added to either mycophenolate mofetil or low-dose cyclophosphamide. Belimumab is one of the safest biologics studied for lupus, she said. In an earlier phase 2 trial of voclosporin, 11.3% of patients in the most effective dosing group died, compared to 1.1% in the placebo group. But this year, the larger and longer phase 3 trial of the drug reported no differences in either deaths or serious adverse events.³

Dr. Merrill pointed to a recent study of lupus patients as an example of using patterns of gene expression in immunologic pathways to help individualize and guide more optimal treatment.⁴

“We’re learning to simplify this confusing heterogeneity of lupus into some kind of patterns that may become very useful clinically,” she said.

Dr. Putterman

New Biomarkers
Chaim Putterman, MD, associate dean of research at the Azrieli Faculty of Medicine of Bar-Ilan University, Safed, Israel, and professor of medicine and microbiology and immunology the Albert Einstein College of Medicine and Montefiore Medical Center, New York, said better biomarkers are needed to differentiate lupus from other diseases, identify specific organ involvement, measure disease activity and predict who will respond to certain treatments.

Anti-double stranded DNA antibodies and complement components are still the most reliable biomarkers commercially accessible, Dr. Putterman said. Recent research found patients with renal tubular complement C9 staining had significantly higher proteinuria, interstitial fibrosis and chronic disease activity. Patients with glomerular C9 were more likely to be nonresponders to treatment after adjusting for blood pressure, treatment compliance and proteinuria.^5,6

The era of big data holds promise for better biomarkers, he said. Several proteins in urine, including angiopoietin-like 4 and L-selectin, have been found to be highly associated with disease activity and useful in tracking pending flares.⁷

Researchers are now testing itolizumab, which modulates a pathway involving CD6 and activated leukocyte cell adhesion molecule (ALCAM)/CD166, a urine protein identified using proteomics.

The goals of precision medicine using biomarkers, Dr. Putterman said, “are most likely to be realized through big data approaches rather than traditional, hypothesis-driven, single-mediator research.”