Treat-to-Target Strategy Has Treatment Potential in Pediatric Lupus Nephritis

Treat-to-target has long been used in adults, but a new study finds it is warranted in pediatric cases, too.

A new study suggests the treat-to-target (T2T) strategy, long in use to treat adult patients with systemic lupus erythematosus (SLE), should be used to manage pediatric patients who experience lupus nephritis (pLN).

The report, published in Pediatric Nephrology, is based on a retrospective analysis of 220 patients of a children’s hospital in China who received their LN diagnosis between 2012 and 2018.

The authors explained that about 1 in 5 cases of SLE appears in childhood and that one of the most common complications of SLE is LN.

“LN has various clinical manifestations and pathological types in children, varying from mild hematuria or proteinuria to nephrotic syndrome and kidney failure, which brings difficulties in clinical diagnosis and treatment of pLN,” the authors wrote.

Children with SLE can also be affected by the toxicity associated with long-term use of corticosteroids and immunosuppressive drugs.

In adults, neuropsychiatric lupus and infection are among the main causes of death, prompting a move to treat LN not just by focusing on renal remission, but also by controlling disease activity, preventing organ damage, and minimizing comorbidities. Since 2014, T2T has been used in adults, focusing on targets such as remission and low disease activity state (LDAS). The investigators said that strategy has appeared to be effective, but it has not yet been tried in pediatric patients.

To better understand how such a strategy might work in children, they analyzed the cohort of 220 patients, wanting to know their clinical manifestations, renal pathological characteristics, and outcomes. They also examined overall remission to better understand how the T2T strategy might work in children. Complete follow-up data were available for 137 patients, and 173 patients had follow-up data that went beyond 6 months.

The analysis showed that the most common pLN manifestation was proteinuria (81.36%), and the most common grade of LN was class IV (33.33%), based on kidney biopsy.

“​​Of initial nonrenal manifestations, fever and rash were the most common,” the investigators found. “Compared with adult patients, symptoms such as oral ulcers and alopecia in pediatric patients were relatively rare.”

Female patients were more likely to have rash and alopecia than males, they also found.

At a median follow-up of 27.2 months, the data showed a 1-year cumulative overall survival rate of 93.5%. By 3 years, the rate fell to 87.8%. At 5 years, 86.5% of patients had survived. Cumulative kidney survival at 5 years was 97.1%.

The authors said patients initially treated with corticosteroids plus immunosuppressive agents had significantly better outcomes than those treated with corticosteroids alone. A logistic regression analysis showed hypertension, nervous system involvement, treatment noncompliance, and lower estimated glomerular filtration rate at diagnosis all affected patient prognosis.

At the end of follow-up, about one-third of patients had achieved some level of remission, and 8.76% of patients were in LDAS, the authors said, lower rates than are typically achieved in adults.

“Compared with adults, children are more active in SLE and receive more intensive immunosuppressive therapy,” they wrote. “Even if the disease is in remission, it is mostly clinical remission on therapy, meaning that long-term use of steroids and immunosuppressants is toxic and accumulates more organ damage over time.”

The investigators said physicians need to be observant for systemic damage and use the T2T strategy to manage pediatric patients, adding that there are new treatment options, including emerging therapies like rituximab (Rituxan) and belimumab (Benlysta).

The authors said while the T2T strategy ought to be leveraged in pediatric patients, there is also a need for further research to better understand long-term outcomes and optimal targets in this patient population.

Reference

Qiu S, Zhang H, Yu S, et al. Clinical manifestations, prognosis, and treat-to-target assessment of pediatric lupus nephritis. Pediatr Nephrol. Published online August 11, 2021. doi:10.1007/s00467-021-05164-y