Baseline Factors May Predict Overall, Renal Response to Therapy in SLE

A new analysis of systemic lupus erythematosus (SLE) clinical trial data has identified several factors that may help clinicians better predict which patients are most likely to respond to treatment at 6 months.

In a study published in Lupus Science & Medicine, investigators concluded that a longer duration of nephritis and higher proteinuria were associated with poorer renal response and active nonrenal disease and higher baseline damage were associated with poorer overall SLE response to treatment.

Most patients with SLE will develop lupus nephritis, and about 15% of those patients will eventually develop end-stage renal disease after a decade. Yet, the authors wrote that the immunosuppressive drugs primarily used to treat these patients often have modest results and significant adverse effects. Thus, one unmet need is figuring out better ways to identify which patients are most likely to respond to therapy, they explained.

“Developing a more personalized approach to treatment may help mitigate longer-term complications,” they wrote.

The investigators decided to use data from the Aspreva Lupus Management Study, a global study that compared mycophenolate mofetil (MMF; CellCept) to intravenous cyclophosphamide as induction therapy for patients with lupus nephritis. Their goal was to identify factors associated with overall treatment response at 6 months and to see whether any characteristics predisposed patients to renal response, specifically.

A total of 370 patients were included in the analysis. About half (50.81%) showed improvement at 6 months. Those patients were more likely to be older (odds ratio [OR], 1.03; 95% CI, 1.01-1.05) and have normal hemoglobin (OR, 1.85; 95% CI, 1.16-2.95). However, several factors were predictive of a poor treatment response, including active disease in hematological (OR, 0.61; 95% CI, 0.39-0.97) and mucocutaneous (OR, 0.50; 95% CI, 0.31-0.81) domains of the British Isles Lupus Assessment Group Index. Baseline damage and 24-hour urine protein were also linked with poor overall response.

In terms of renal response, just 20.27% of patients achieved a complete renal response by 6 months. The authors found that 24-hour urine protein (OR, 0.63; 95% CI, 0.45-0.89) and a lupus nephritis duration of 2 to 4 years vs less than 1 year (OR, 0.43; 95% CI, 0.19-0.97) were negative predictors of complete renal response. The study also showed that patients from Latin American countries were less likely to have a complete renal response, a the authors said is consistent with other research suggesting patients of Hispanic backgrounds tend to develop lupus nephritis more quickly and have more aggressive disease.

The investigators said it was notable that there were different predictors of renal response vs overall response.

“This observation is relevant to future [lupus nephritis] trials, as balancing nonrenal manifestations may influence overall outcomes since trials assess both renal and nonrenal changes in their outcome assessments,” they wrote.

Still, they said their findings have significant limitations. Despite the global nature of the data set, it still had just 370 patients included and 12-month response data were not available for all patients. And although their analysis found baseline factors associated with treatment response, the authors cautioned that the predictive power of these factors was modest.

“Taken together, our results emphasize the need to identify novel biomarkers that will improve the predictive accuracy for treatment response in patients with SLE over and above the modest performance of clinical factors alone,” they said.

Reference

McDonald S, Yiu S, Su L, et al. Predictors of treatment response in a lupus nephritis population: lessons from the Aspreva Lupus Management Study (ALMS) trial. Lupus Sci Med. Published online May 2022. doi:10.1136/lupus-2021-000584