Background Efficacy of the Euro-lupus nephritis regimen with low dose intravenous cyclophosphamide (LDCY) followed by AZA maintenance (ELN) has previously been established in predominately Caucasian European lupus nephritis patients. The ELN regimen has not been examined in racially/ethnically diverse populations.
Objectives The ACCESS study assessed the efficacy of the ELN regimen combined with either placebo or with abatacept (ABA) in North America.
Methods Subjects with biopsy class III or IV lupus nephritis (w/without class V) and urine protein:creatinine ratio (UPCR) >1 were enrolled. All subjects received LDCY (500 mg q 2 wks × 6) followed by AZA (2 mg/kg/d up to a maximum of 200 mg/dose). Subjects were randomized 1:1 to receive saline (n=68) or ABA (n=66) IV at weeks 0, 2, 4, and then every 4 weeks. ABA was dosed based on weight: <60 kg, 500 mg; 60-100 kg, 750 mg; >100 kg, 1 gm. Subjects received standard oral prednisone from 60 mg/d tapered to 10 mg/d within 12 weeks. AZA maintenance therapy was discontinued in subjects in the ABA group who achieved a complete response (CR) at week 24. The primary outcome measure was CR at 24 weeks, defined as: UPCR <0.5; serum creatinine normal or, if abnormal, within 25% of baseline; and adherence to the steroid regimen. Partial response (PR) required a >50% improvement in UPCR and the remaining CR criteria AZA maintenance therapy was discontinued in the ABA group with CR at 24 weeks.
Results A racially/ethnically diverse population of North American subjects was enrolled (39% African American, and 40% Hispanic/Mestizo).The groups were matched for race, ethnicity, severity of nephritis, and biopsy class. At 24 weeks, the CR rate in the ABA group was 22/66 (33%) vs 21/68 (31%) in the control group (p=0.85). Total response (CR+PR) TR in the ABA and control group was 59% (39/66 vs 40/68). There was no difference between the groups at week 24 in mean UPCR, anti-dsDNA and complement levels, BILAG score, SF-36, frequency of serious adverse events (SAEs), or withdrawals. Among African American subjects, 33% (9/27) of subjects in the ABA group achieved CR, compared to 19% (5/26) in the control group (p=0.20). In the Hispanic/Mestizo group 32% (8/25) in the ABA group and 32% (9/28) in the control group achieved CR. TR among African American subjects in ABA group was 15/27 (56%) vs 16/26 (62%) in the control group; among Hispanic/Mestizo, in ABA group 15/25 (60%) compared to 14/28 (50%). Patient global assessment improved by 74% in the ABA group vs 38% in the control group (p=0.051). At week 52, 50% (11/22) of the CR in the ABA group remained in CR and, 62% (13/21) in the control group.
Conclusions The ACCESS trial did not demonstrate a benefit for ABA plus ELN compared to ELN alone at 24 weeks. No differences were observed in CR or total response (CT+PR) between ABA vs control group by race/ethnicity. However, the ELN regimen in this racially and ethnically diverse population achieved a response rate >30% CR within 24 weeks, higher than reported in prior lupus nephritis trials suggesting that the ELN regimen may have broad applicability. Subjects in the ACCESS trial are still undergoing evaluation to examine outcome at later time points.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.