Background/Purpose  Lupus nephritis (LN) is a major complication of systemic lupus erythematous (SLE) and prevalence is estimated to be 50-60%. Recently, variable responses to induction regimes have been observed in different ethnic groups with Hispanics and Blacks tending to respond better to Mycophenolate Mofetil (MMF) than intravenous cyclophosphamide (CYC) (1). Limited data is available for Asians from the Indian Subcontinent. Our aim was to examine retrospectively the influence of ethnicity on LN outcome in our large single centre cohort of SLE patients.   

Methods We identified 119 SLE patients with biopsy proven LN diagnosed 1992-2013 from our electronic database. LN classes based on glomerular pathology were defined according to the ISN/RPS classification. Complete remission (CR) was defined as 24-hour proteinuria <0.5g. Clinical and laboratory data were obtained from patient records.  

Results   Of 119 LN patients, 80 (67%) had proliferative LN (class III or IV, of which 21% had concomitant membranous, class V lesions). Among those, 16 were male (20%) and 64 female (80%). 35 were African black or Afro-Caribbean (44%), 28 were Asians from the Indian Subcontinent (35%), and 17 were Caucasians (21%). The median age was 27 years (IQR, 20-38) at SLE diagnosis and 31 years (IQR, 24-40) at LN diagnosis. There was no difference in baseline characteristics among ethnic groups, apart from increased frequencies of ENA antibodies in Blacks compared to Caucasians, specifically RNP (n=18, 54.5% vs. n=2, 11.8%; p=0.000) and Sm antibodies (n=13, 39% vs. n=1, 6%; p=0.002). The main induction regimes were CYC given either intravenously or orally (n=49, 61%; with a median 6-month cumulative dose of 6.3g, IQR, 3-9), or MMF (n=25, 31%; with target dose 3g/day). All patients had a tapering course of high dose corticosteroids. At 6 months, CR was achieved in 13 patients (46%) in the Asian subgroup, in 10 (31%) in the Black subgroup and in 8 (47%) in Caucasians. At 24 months, 16 Asians (67%), 14 Blacks (61%) and 10 Caucasians (83%) reached CR. At 6 months, MMF achieved a higher rate of CR in Blacks than CYC (n=7, 70% vs. n=3, 23%, respectively; p=0.024) and showed a trend in Asians (n=6, 75% vs. n=7, 41%, respectively; p=0.114). In contrast, in Caucasians, CR rate was similar in both treatment arms at 6 months (n=5, 56% in CYC vs. n=3, 50% in MMF, p=0.833). At month 24, there was a non-statistical trend for greater response to MMF than CYC in Asians and Blacks, but not in Caucasians. Up to date, 20 patients (25%) have developed end-stage kidney disease with the highest rate in Blacks (n=13, 37%). Severe infections tended to be more common in patients treated with CYC than MMF (n=7, 15% vs. n=2, 8%; p=0.642). CYC caused gonadal toxicity in 6 patients (14%).

Conclusion Current ACR guidelines (2) recommend using MMF rather than CYC for LN class III/IV induction therapy in African Americans and Hispanics. Our retrospective study provides supportive evidence that MMF tends to achieve higher remission rates in Blacks, and is at least as effective as CYC in Caucasians and Asians from the Indian Subcontinent, with fewer adverse events.

1. Isenberg D, Rheumatology 2010;49:128-140

2. Hahn BH, Arthritis Care Res 2012;64(6):797-808

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/influence-of-ethnicity-on-efficacy-of-current-immunosuppressive-protocols-in-proliferative-lupus-nephritis/