Low Rates of Sustained Treatment Response in Lupus Nephritis Highlight Need for Improved Therapies – Renal and Urology News

The 52-week complete response (CR), partial response (PR), and combined CR and PR rates of patients in the Accelerating Medicines Partnership Lupus Nephritis (AMP LN) cohort mirror the standard of care/placebo response rates seen in recent LN trials, according to study results published in Arthritis Research & Therapy.

The AMP Rheumatoid Arthritis/Systemic Lupus Erythematosus (SLE) Network aims to enhance LN outcomes using advanced technologies. The AMP LN cohort includes a diverse population of patients in the United States with LN who underwent standard of care kidney biopsies.

Investigators carried out a multicenter prospective cohort study utilizing data from the AMP LN cohort. They assessed the proportion of patients who achieved responder status, longitudinal response patterns, and predictors of clinical response among patients with LN receiving standard of care therapy. Eligible participants included those with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio of at least 1.0.

Response thresholds were defined as:

• CR: a UPCR less than 0.5; normal serum creatinine levels (≤1.3 mg/dL) or those equal to or less than 125% of baseline value if abnormal; and prednisone dosages of 10 mg/day or less
• PR: a greater than 50% reduction in UPCR; normal serum creatinine levels (≤1.3 mg/dL) or those equal to or less than 125% of baseline value if abnormal; and prednisone dosages of 15 mg/day or less
• Nonresponders (NR)/Not Determined (ND): patients who did not receive a CR or PR

A total of 180 patients from the AMP LN cohort were included in the final analysis. The cohort predominantly consisted of women (86.7%) with a mean patient age of 35.2 years. The mean baseline UPCR was 3.5. In total, 48.3% of patients exhibited extra renal activity on the hybrid Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index at baseline.

Week 52 response rates to standard of care therapy were 22.2% for CR, 21.7% for PR, 41.7% for NR, and 14.4% for ND. Out of 180 patients, only 4.4% achieved a sustained CR from week 12 to week 52, 10% achieved and sustained a PR or CR from weeks 12 to 52, and 26.1% achieved and sustained a PR or CR from weeks 26 to 52.

Achieving a CR or PR by week 52 was linked to several factors: a baseline UPCR greater than 3 (adjusted odds ratio [aOR], 3.71; 95% CI, 1.34-10.24; P =.012), a greater than 25% decrease in UPCR from baseline to week 12 (aOR, 2.61; 95% CI, 1.07-6.41; P =.036), a lower chronicity index (aOR, 1.33 per unit decrease; 95% CI, 1.10-1.62; P =.003), and the presence of positive anti-dsDNA antibodies (aOR, 2.61; 95% CI, 0.93-7.33; P =.069).

According to exploratory analyses that separately considered CR, PR, and NR statuses at week 52, baseline positive anti-dsDNA antibodies, a greater than 25% decrease in UPCR from baseline to week 12, and the chronicity index were discriminators for CR vs NR status. Moreover, a UPCR greater than 3 at baseline was identified as a discriminator for PR vs NR status.

Study limitations included potential underestimation of steroid doses, incomplete capture of changes in immunosuppression, constraints in analyzing medication changes, and the small sample size for sustained response analyses.

“Low sustained CR rates not only underscore the need for more efficacious therapies but highlight how critically important it is to understand the molecular pathways that are associated with response and non-response,” the study authors noted.

Disclosures: This research was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health.

This article originally appeared on Rheumatology Advisor