SAT0185 Efficacy and safety of abatacept in lupus nephritis. (23rd January 2014)

• Record Type: Journal Article
• 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.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 534
• Page End: 534
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.3132
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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. 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