SAT0185 Efficacy and safety of abatacept in lupus nephritis

• Published in: Annals of the rheumatic diseases Vol. 71; no. Suppl 3; p. 534
• Main Authors: Furie, R., Nicholls, K., Cheng, T.T., Houssiau, F., Burgos-Vargas, R., Chen, S.L., Hillson, J., Meadows-Shropshire, S., Kinaszczuk, M., Merrill, J.T.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2013; BMJ Publishing Group LTD
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2012-eular.3132

Background The evaluation of abatacept (ABA), a modulator of T-cell costimulation, in lupus nephritis (LN) was supported by favorable preclinical studies in murine LN. Objectives To compare the efficacy and safety of IV ABA to placebo (PBO) on a background of mycophenolate mofetil (MMF) and steroids in a 12-month Phase II/III multicenter, double-blind, study of patients (pts) with active Class III or IV LN, including exploratory, post-hoc, and subset efficacy analyses. Methods 298 pts received PBO, ABA 30 mg/kg (30/10), or ABA 10 mg/kg (10/10) in a 1:1:1 ratio on Days 1, 15, 28, 57; thereafter, all ABA pts received 10 mg/kg through Week 48. Prespecified efficacy outcome measures: a) Primary: time to complete response (CR) (CR: eGFR within 10% of preflare/screening; urine protein/creatinine ratio [UPCR] <0.26 g/g; inactive urine: confirmed at 2 consecutive visits); b) CR at Week 52; c) renal improvement (RI) (RI: UPCR <50% of preflare/screening; no worsening of eGFR; inactive urine); d) renal response (RR) (RR: serum creatinine ≤125% of baseline [BL]; UPCR <50% of BL and <3.0 g/g if nephrotic, otherwise <1.0 g/g). Post-hoc efficacy endpoint: CRrev (defined post-hoc to account for renal function misclassifications): eGFR ≥90% of preflare/screening, otherwise same as CR. Results Time to confirmed CR did not differ between groups (p=0.549 and 0.422 for ABA 10/10 and 30/10 vs PBO). Efficacy at Week 52 is shown (Table). Subset analyses of 122 nephrotic pts (BL UPCR >3.0 g/g) found approximately 20–30% greater reduction in mean UPCR. Safety, assessed as deaths, serious adverse events (SAEs) and serious infections, was similar across groups. AEs were generally mild, self-limited and similar in frequencies across groups, with the exception of Herpes zoster (reported in 2.0%, 11.1%, 8.1% of PBO, ABA 10/10, ABA 30/10, respectively). Post-hoc subset analyses suggested Asian race and early reduction of proteinuria (8–12 weeks) were associated with response (CRrev and RR at Week 52) in all groups. Efficacy: Treatment groupPlaceboABA 10/10ABA 30/10 TreatedN=100ABA 10/10 N=99N=99 Confirmed CR at Month 12, %3.03.05.1 CR at Month 12, %8.010.110.1 RI at Month 12, %55.052.555.6 RR at Month 12, %33.039.445.5 Post-hoc: CRrev at Month 12, %12.022.215.2 Conclusions Abatacept and PBO, administered on a background of MMF and steroids to pts with LN, exhibited similar safety profiles, time to confirmed CR, and proportion with CR and RI. Exploratory and post-hoc analyses indicated more complete (CRrev) and renal (RR) responders with abatacept compared to PBO. Disclosure of Interest R. Furie Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, K. Nicholls: None Declared, T. Cheng: None Declared, F. Houssiau: None Declared, R. Burgos-Vargas Grant/Research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, S. Chen: None Declared, J. Hillson Employee of: Bristol-Myers Squibb, S. Meadows-Shropshire Employee of: Bristol-Myers Squibb, M. Kinaszczuk Employee of: Bristol-Myers Squibb, J. Merrill Consultant for: Bristol-Myers Squibb