#2898 UNMET NEEDS AND POOR LONG-TERM RENAL OUTCOMES IN EUROPEAN PATIENTS WITH LUPUS NEPHRITIS
Authors: Barratt Jonathan , Ma Janice , Pisarczyk Konrad , Park Eunmi , Palaniswamy Kiruthi , Leff Richard 
Published: June 2023

Abstract

Background and Aims
Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), associated with substantial morbidity and increased risk of end-stage renal disease (ESRD). Despite currently used therapies, a notable proportion of patients may not achieve sustained remission, leading to adverse disease outcomes. This study aims to summarize evidence on the long-term outcomes, burden of comorbidities, and real-world (RW) effectiveness of therapy in European patients with LN.

Method
A targeted literature review was conducted using MEDLINE/Pubmed and Embase to identify studies in patients with LN. Search strategies were developed for each database to identify relevant peer-reviewed articles published in English from March 2012 - March 2022 and conference abstracts from 2019 – March 2022. All records were screened according to pre-specified inclusion/exclusion criteria. Only studies conducted in a European setting were summarized here.

Results
Of 4,216 total records, 55 studies reported long-term outcomes of LN and RW effectiveness of treatment in European adults. Up to 36% of patients with SLE developed LN, and nearly all LN cases occurred within 5 years of SLE diagnosis. Patients with LN often suffered from serious infection (19-35%), cardiovascular disease (CVD) (26%), chronic kidney disease (CKD)/ESRD (6-22%) and were more likely to experience cardio- and cerebrovascular events than patients with SLE only (p = 0.001). Patients with LN had a higher risk of mortality compared to those with SLE only or other lupus manifestations (p&lt;0.001), and deaths were often due to infections (8-32%), CVD (22-58%), or malignancies (5-27%). CKD/ESRD also contributed to poor survival – patients with ESRD had 3-times higher risk of death compared to those with LN only (p&lt;0.001). The majority of RW studies evaluated effectiveness of standard of care (SOC) induction and/or maintenance therapy, mostly with mycophenolate mofetil and cyclophosphamide. Treatment response rates varied across the studies likely due to heterogeneity in study design, drug dosing, and patient population; comparative studies did not find significant differences in response rates between the regimens. Overall, 30-86% of patients with LN achieved complete renal response/remission (CRR) within the first year of starting SOC therapy. However, one study reported that only 38% of patients maintained CRR while on SOC over a 5-year period, suggesting inadequate long-term maintenance on existing therapies. Patients who were non-responders (NR) after 1 year had a significantly increased risk of mortality and CKD compared to responders (p&lt;0.005). Patients achieving CRR had significantly longer CKD-free survival compared to NR at 15 years (95% vs 55%, p&lt;0.0001), further highlighting the value of achieving response in terms of long-term renal outcomes. Despite initial response to current therapies, 20-35% of patients experienced a renal relapse/flare while on maintenance therapy, with one study noting significantly increased risk of proteinuric flares with azathioprine compared to other maintenance therapies (p = 0.01). Limited studies focused on treatment-experienced/refractory patients, with the majority evaluating rituximab (RTX)-based regimens. After one year of therapy, 29-64% of patients with refractory LN and 35% of patients with active LN despite SOC achieved CRR on RTX or belimumab, respectively.

Conclusion
European adults with LN have considerable comorbidity burden and poor long-term renal outcomes. Few patients achieve and maintain remission on SOC, and a notable proportion of patients experience renal relapse despite initial response to therapy. Given the impact that achieving CRR has on long-term outcomes, there is a need for effective therapies that provide sustained remission, especially for patients with severe/refractory LN.