ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 971

A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept or Placebo on Standard of Care in Patients with Active Class III or IV Lupus Nephritis

Mary A. Dooley1, Gerald B. Appel2, Richard Furie3, David Wofsy4, Tsutomu Takeuchi5, Ana Malvar6, Andrea Doria7, Juanita Romero-Díaz8, Tak Mao Chan9, Ayanbola Elegbe10, David Jayne11 and Michael A. Maldonado10, 1University of North Carolina at Chapel Hill, Chapel Hill, NC, 2Columbia University Medical Center, New York, NY, 3Northwell Health, New York, NY, 4University of California San Francisco, San Francisco, CA, 5Keio University School of Medicine, Tokyo, Japan, 6Nephrology Division, Hospital Fernández, Buenos Aires, Argentina, 7Division of Rheumatology, University of Padova, Padova, Italy, 8Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico, 9University of Hong Kong, Hong Kong, Hong Kong, 10Bristol-Myers Squibb, Princeton, NJ, 11University of Cambridge, Cambridge, United Kingdom

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Date: Sunday, October 21, 2018

Session Title: 3S110 ACR Abstract: SLE–Clinical I: Clinical Trials (970–975)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: The tenets of novel treatment (tx) strategies for active class III/IV lupus nephritis (LN) aim to improve renal response rates, decrease extra-renal SLE disease activity and provide an acceptable tx-related safety profile. The study compared efficacy and safety of IV abatacept (ABA) vs placebo (pbo) on background therapy for active proliferative LN.

Methods: This was a 24-month (M), randomized, Phase III, multicenter, double-blind study with a blinded long-term extension. Patients (pts) were randomized 1:1 to pbo or IV ABA 30 mg/kg for 3M, followed by ABA ~10 mg/kg every 4 wks on a background of mycophenolate + corticosteroids (CS). Primary endpoint, complete renal response (CR) at 1 yr, was a composite measure requiring maintenance of glomerular filtration rate (GFR), urine protein-to-creatinine ratio (UPCR) ≤0.5, absence of urinary cellular casts and CS ≤10 mg/day. We report all blinded data up to 3 yrs of tx (as-observed analysis). Results: 405 pts were randomized (ABA n=202, pbo n=203). At baseline mean age=33 yrs, mean UPCR=3.78, mean eGFR=95 mL/min. Yr 1 study completion rates: ABA 77%, pbo 79%; fewer ABA pts discontinued in Yr 2 (ABA 14%, pbo 22%) and beyond. There were no significant differences between tx arms in proportion of pts with CR after 52 wks of tx (ABA 35.1%, pbo 33.5%, p=0.73). Sustained CR (2 successive visits) occurred earlier and more frequently in ABA-treated pts (Fig 1). Renal response rates were higher and non-response rates were lower in ABA arm in Yr 2 and 3. These benefits were driven by improvement in proteinuria seen as early as 3M and sustained up to 3 yrs (Fig 2). There was no between-group difference in eGFR over 3 yrs. Few non-renal adjudicated BILAG A or B events occurred in Yr 1 and over 3 yrs; BILAG scores were lower in ABA arm. Safety in Yr 1 was consistent with known profile of ABA (serious AE [SAE] rate: ABA 24%, pbo 19%). SAE rates after Yr 1 improved (ABA 6%, pbo 13%). Deaths over 3 yrs were equal (7 each). Greater improvements in SLE-related biomarkers (C3, C4, anti-dsDNA autoantibodies) were sustained in ABA-treated pts over 3 yrs (Fig 3).

Conclusion: The study failed to meet its primary endpoint of higher CR rate in pts with active LN after 1 yr of abatacept tx. Abatacept-treated pts had more rapid improvement in proteinuria, which led to more sustained CR up to 3 yrs. There were favorable efficacy and safety profiles in Yr 2 and 3 of abatacept tx.


         

Disclosure: M. A. Dooley, None; G. B. Appel, Bristol-Myers Squibb, 2; R. Furie, Bristol-Myers Squibb, 2, 5; D. Wofsy, GSK, Novartis, Takeda and Celgene, 5; T. Takeuchi, Astellas Pharma Inc, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., 2,Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc,. Taiho Pharmaceutical Co., Ltd.,, 5,AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Astellas Pharma Inc, and Diaichi Sankyo Co.,Ltd., 8,Taisho Toyama Pharmaceutical Co., Ltd., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co.Ltd, 2; A. Malvar, None; A. Doria, AstraZeneca, Baxalta, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, 5,Bristol-Myers Squibb, GSK, Eli Lilly, 8; J. Romero-Díaz, None; T. M. Chan, Astellas, Novartis, Boehringer Ingelheim, 5,Astellas, 2; A. Elegbe, Bristol-Myers Squibb, 3; D. Jayne, GSK, Roche, Sanofi, 2,Aurinia, Boehringer Ingelheim, Chemocentryx, CSL, GSK, Inflx, Medimmune, Takeda, Sanofi, 5; M. A. Maldonado, Bristol-Myers Squibb, 1, 3.

To cite this abstract in AMA style:

Dooley MA, Appel GB, Furie R, Wofsy D, Takeuchi T, Malvar A, Doria A, Romero-Díaz J, Chan TM, Elegbe A, Jayne D, Maldonado MA. A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept or Placebo on Standard of Care in Patients with Active Class III or IV Lupus Nephritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/a-phase-iii-randomized-double-blind-placebo-controlled-study-to-evaluate-the-efficacy-and-safety-of-abatacept-or-placebo-on-standard-of-care-in-patients-with-active-class-iii-or-iv-lupus-nephritis/. Accessed April 2, 2020.

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