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Randomized Controlled Trial
. 2023 Nov 30;38(12):2733-2742.
doi: 10.1093/ndt/gfad167.

Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial

Hans-Joachim Anders  1 , Richard Furie  2 , Ana Malvar  3 , Ming-Hui Zhao  4 , Keiju Hiromura  5 , Julia Weinmann-Menke  6 , Yulia Green  7 , Angela Jones-Leone  8 , Daniela Negrini  9 , Roger A Levy  8 , Liz Lightstone  10 , Yoshiya Tanaka  11 , Brad H Rovin  12
Affiliations
Randomized Controlled Trial

Effect of belimumab on kidney-related outcomes in patients with lupus nephritis: post hoc subgroup analyses of the phase 3 BLISS-LN trial

Hans-Joachim Anders et al. Nephrol Dial Transplant. .

Abstract

Background: Data on belimumab efficacy in patients with lupus nephritis (LN) according to diagnosis duration or induction therapy are limited. Post hoc analyses of the phase 3, randomized, double-blind BLISS-LN study (GSK BEL114054; NCT01639339) were performed to assess belimumab efficacy on kidney-related outcomes in newly diagnosed and relapsed LN subgroups and according to the use of glucocorticoid (GC) pulses at induction.

Methods: BLISS-LN randomized 448 patients with active LN to monthly intravenous belimumab 10 mg/kg or placebo plus standard therapy. Post hoc analyses assessed primary efficacy renal response (PERR) and complete renal response (CRR) at week 104, time to kidney-related event or death and time to first LN flare from week 24 in newly diagnosed and relapsed patients and patients with/without GC pulses at induction.

Results: A greater proportion of patients achieved a PERR with belimumab versus placebo in the newly diagnosed {69/148 [46.6%] versus 55/148 [37.2%]; odds ratio [OR] 1.36 [95% confidence interval (CI) 0.85-2.20]} and relapsed [27/75 (36.0%) versus 17/75 (22.7%); OR 2.31 (95% CI 1.07-5.01)] subgroups. Similarly for CRR [newly diagnosed: 50/148 (33.8%) versus 36/148 (24.3%); OR 1.49 (95% CI 0.88-2.51) and relapsed: 17/75 (22.7%) versus 8/75 (10.7%); OR 3.11 (95% CI 1.16-8.31)]. The probability of kidney-related event or death, or LN flare was lower with belimumab versus placebo in both subgroups. Belimumab was associated with improved kidney outcomes versus placebo with or without GC pulses at induction.

Conclusion: Data suggest consistent benefits of belimumab on kidney outcomes for newly diagnosed and relapsed patients, and irrespective of GC pulses at induction.

Keywords: B cells; belimumab; glucocorticoids; lupus nephritis; proteinuria.

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Conflict of interest statement

H.-J.A. has received consultancy fees or honoraria from AstraZeneca, Bayer, Boehringer, GSK, Idorsia, Janssen, Kezar, Sanofi, Otsuka, Novartis and PreviPharma; is a member of the Scientific Advisory Board of the European Renal Association and an associate editor at Journal of the American Society of Nephrology and NDT. R.F. has received advisory board fees and travel support from GSK. L.L. has received consulting fees from Alexion, AstraZeneca, Biogen, Bristol-Myers Squibb, GSK, Kezar, Novartis and Pfizer; honoraria from Alexion, AstraZeneca, Bristol-Myers Squibb, GSK and Novartis; serves as Chair, DMC of a trial in LN for Novartis and Deputy Chair for the Western Europe Regional Board, ISN; Member ExCom ISN, Trustee Kidney Research UK. A.M. has received consultancy fees from GSK, Roche and Biogen. M.-H.Z. has received consultancy fees from AstraZeneca, GSK, Kira, Novartis and Roche. K.H. has received consultancy fees from GSK; grant/research support from Bayer, Chugai, GSK and Kyowa Kirin and honoraria from Astellas, AstraZeneca, Chugai, GSK and Sanofi. J.W.-M. participated in advisory boards and has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Novartis and Otsuka. Y.T. has received speaker fees and/or honoraria from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Mitsubishi-Tanabe and Pfizer and has received research grants from AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai and Takeda. B.H.R. has received grants or contracts from Biogen, National Institute on Aging, National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Diabetes and Digestive and Kidney Diseases; consulting fees from Aurinia, Alexion, AstraZeneca, Biocryst, Biogen, Bristol-Myers Squibb, Calliditas, Chemocentryx, Corrona, EMD Serono, Exagen, Galapagos, Genentech-Roche, GSK, Janssen, Kezar, Lilly, Morphosys, Novartis, Omeros, Otsuka, Pfizer, Travere and the University of Minnesota; honoraria for Medicine, Nephrology, Rheumatology Grand Rounds Lectures at various academic centres; support for attending meetings from the American Society of Nephrology and leadership/fiduciary roles for the Lupus Foundation of American and Kidney Disease: Improving Global Outcomes Glomerulonephritis Guideline. A.J.-L., Y.G. and R.A.L. are employees of GSK and hold stock and shares in the company. D.N. was a contract worker at GSK at the time of the study.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
PERR and CRR at week 104 in patients with relapsed and newly diagnosed LN (mITT population; post hoc analyses). OR and 95% CI values are from a logistic regression model run within the subgroup level for the comparison between belimumab and placebo with covariates treatment group, induction regimen (CYC versus MMF), race (Black African ancestry versus other), baseline UPCR and baseline eGFR.
Figure 2:
Figure 2:
Time to kidney-related event or death through week 104 in patients with newly diagnosed and relapsed LN (mITT population; post hoc analyses). HR and 95% CI values are from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for induction regimen (CYC versus MMF), race (Black African ancestry versus other), baseline UPCR and baseline eGFR. Investigational product discontinuations, treatment failures not related to kidney disease and withdrawals were censored on the date of the event. Patients who completed the study were censored at week 104.
Figure 3:
Figure 3:
Time to first LN flare from week 24 in patients with newly diagnosed and relapsed LN (mITT population among patients on treatment at week 24; post hoc analyses). aWeek 24 values are used as ‘baseline’ in the definition of LN flare. HR and 95% CI values are from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for induction regimen (CYC versus MMF), race (Black African ancestry versus other), week 24 UPCR and week 24 eGFR. Investigational product discontinuations, treatment failures not related to kidney disease and withdrawals were censored on the date of the event. Patients who completed the study were censored at week 104. Renal-related treatment failures were considered flares.
Figure 4:
Figure 4:
PERR and CRR at week 104 in patients with and without GC pulses at induction (mITT population; post hoc analyses). OR and 95% CI values are from a logistic regression model run within the subgroup level for the comparison between belimumab and placebo with covariates treatment group, induction regimen (CYC versus MMF), race (Black African ancestry versus other), baseline UPCR and baseline eGFR.
Figure 5:
Figure 5:
Time to kidney-related event or death through week 104 in patients with and without GC pulses at induction (mITT population; post hoc analyses). HR and 95% CI values are from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for induction regimen (CYC versus MMF), race (Black African ancestry versus other), baseline UPCR and baseline eGFR. Investigational product discontinuations, treatment failures not related to kidney disease and withdrawals were censored on the date of the event. Patients who completed the study were censored at week 104.
Figure 6:
Figure 6:
Time to first LN flare from week 24 in patients with and without GC pulses at induction (mITT population; post hoc analyses). aWeek 24 values are used as ‘baseline’ in the definition of LN flare. HR and 95% CI values are from Cox proportional hazards model for the comparison between belimumab and placebo adjusting for induction regimen (CYC versus MMF), race (Black African ancestry versus other), week 24 UPCR and week 24 eGFR. Investigational product discontinuations, treatment failures not related to kidney disease and withdrawals were censored on the date of the event. Patients who completed the study were censored at week 104. Renal-related treatment failures were considered flares.
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