Biomarkers and Biologics Key to Better Outcomes in Children With LN

A treat-to-target approach and better understanding of biologic pathways could help improve outcomes for patients with juvenile-onset systemic lupus erythematosus (JSLE), which often progresses to lupus nephritis (LN), investigators from the United Kingdom suggest.

The research team noted that more than 50% of children with JSLE have some kidney involvement. “Several international groups have produced treatment protocols that rely on an intense period of immunosuppression to halt the acute kidney inflammatory process, followed by maintenance therapy with close observation for disease improvement and prompt evaluation of disease flares,” they wrote in Pediatric Nephrology.

The intense suppression of the immune system required to control LN heightens the risk of serious infection, which is the leading cause of death among patients with JSLE. Mortality rates among patients with JSLE are closely associated with active LN, the authors stated, “with the major predictor of mortality being the serum creatinine at the time of clinical presentation” among children who participated in a study conducted in India.

Improving outcomes will require “require further scientific understanding of the biological pathways involved in active LN, and a clinically robust method of immune cell profiling that is designed and based around existing biological therapies,” the investigators stated. They suggested that immune profiling of patients who do not achieve complete remission could identify components—including B cell, cytokines, and complement products—that can provide targets for a treat-to-target strategy. 

Biologic therapies have been found effective in treating LN, the researchers stated, with agents now being investigated in therapy for JSLE and LN including  obinutuzimab, belimumab, atacicept, anifrolumab, tocilizumab, eculizumab, dapirolizumab, and abatacept.

“Future research should focus on discovering early disease biomarkers, including surrogates for later cardiovascular disease, and evaluating biological agents as adjuncts to improve the rates of complete remission and subsequently influence the kidney outcome,” the authors concluded.

--Rebecca Mashaw

Reference:

Oni L, Wright RD, Marks S, Beresford MW, Tullus K. Kidney outcomes for children with lupus nephritis. Pediatric Nephrology 2021;36: 1377–1385