Attainment of EULAR/ERA-EDTA targets of therapy with current immunosuppressive regimens and adjustments in treatment: a multicentre, real-life observational study

Abstract

Objective: To estimate real-life European Alliance of Associations for Rheumatology (EULAR)/European Renal Association (ERA)-European Dialysis and Transplantation Association (EDTA) response rates and predictors for no response in patients with lupus nephritis (LN) managed with conventional immunosuppressive therapies.

Methods: Ambidirectional cohort study of patients with new-onset LN (period 2014-to date). Response rates in the first year were calculated, and all treatment modifications were recorded. Univariate and multivariate regression analyses were performed to assess determinants of failure to respond at 12 months.

Results: 140 patients were included (81.4% women, median (IQR) age at LN diagnosis 38 (22) years). Among them, 32.1% presented with nephrotic range proteinuria, 28.6% with glomerular filtration rate <60 mL/min, 76.6% had proliferative and 19.7% class V LN. Initial treatment consisted of cyclophosphamide in 51.4% of patients (84.7% high-dose, 15.3% low-dose) and mycophenolate in 32.1%. 120 patients had available data at 12 months. EULAR/ERA-EDTA renal response rates at 3, 6 and 12 months were achieved by 72.6%, 78.5% % and 69.2% of patients, respectively. In multivariate analysis, increased Chronicity Index at baseline was associated with failure to achieve either complete or partial response at 12 months (OR 2.26, 95% CI 1.35 to 3.77). Notably, 20% of patients required treatment modifications due to suboptimal response during the first 12 months, with the addition of or switch to a different immunosuppressive drug in seven and nine patients, respectively.

Conclusions: More than two-thirds of patients with LN attain EULAR/ERA-EDTA response rates by 12 months, but 20% require therapy modifications within this time period. Patients with increased chronicity in baseline biopsy, when combined with histological activity, are at higher risk for a lack of clinical response.

Keywords: Cyclophosphamide; Lupus Erythematosus, Systemic; Lupus Nephritis.

Figure 1. (A) More than two-thirds of patients with lupus nephritis achieve the EULAR/ ERA-EDTA treatment target at 12 months. Percentages of attainment of EULAR/ ERA-EDTA treatment targets within the first year after kidney biopsy in patients with lupus nephritis. (B) Rates of partial, complete and no response at 6, 12 and 24 months. Percentages of patients who achieved complete, partial or no response at 6, 12 and 24 months, respectively. EDTA, European Dialysis and Transplantation Association; ERA, European Renal Association; EULAR, European Alliance of Associations for Rheumatology.

Figure 2. Probability for complete response is similar, irrespective of the initial standard-of-care immunosuppressive regimen and lupus nephritis class. Kaplan-Meier survival estimates of probability for complete renal response according to (A) initial treatment regimen (IV CYC vs MMF), and (B) lupus nephritis class. CRR, complete renal response; CYC, cyclophosphamide; IV, intravenous; LN, lupus nephritis; MMF, mycophenolate mofetil.

Figure 3. Immunosuppressive treatment modifications within the first year are not infrequent in lupus nephritis. Flow diagram depicting immunosuppressive treatment modifications within the first year after kidney biopsy in patients with lupus nephritis. Treatment modifications were decided as per the treating physician judgement, either due to inadequate response or due to flare after the initial response.