De novo lupus nephritis during treatment with belimumab

Abstract

Objective In light of reports of de novo LN during belimumab (BLM) treatment, we sought to determine its frequency and contributing or protective factors in a real-life setting. Methods Patients with SLE who received BLM between 2011 and 2017 at five European academic practices were enrolled (n = 95) and followed longitudinally for a median time of 13.1 months [interquartile range (IQR): 6.0–34.7]; 52.6% were anti-dsDNA positive, 60.0% had low complement levels, and 69.5% had no renal involvement prior to/at BLM initiation [mean disease duration at baseline: 11.4 (9.3) years]. Age- and sex-matched patients with non-renal SLE who had similar serological profiles, but were not exposed to BLM, served as controls (median follow-up: 132.0 months; IQR: 98.3–151.2). Results We observed 6/66 cases (9.1%) of biopsy-proven de novo LN (4/6 proliferative) among the non-renal BLM-treated SLE cases after a follow-up of 7.4 months (IQR: 2.7–22.2). Among controls, 2/66 cases (3.0%) of de novo LN (both proliferative) were observed after 21 and 50 months. BLM treatment was associated with an increased frequency and/or shorter time to de novo LN [hazard ratio (HR): 10.7; 95% CI: 1.7, 67.9; P = 0.012], while concomitant use of antimalarial agents along with BLM showed an opposing association (HR: 0.2; 95% CI: 0.03, 0.97; P = 0.046). Conclusion Addition of BLM to standard-of-care did not prevent LN in patients with active non-renal SLE, but a favourable effect of concomitant use of antimalarials was implicated. Studies of whether effects of B-cell activating factor inhibition on lymphocyte subsets contribute to LN susceptibility are warranted.

Early B Cell and Plasma Cell Kinetics Upon Treatment Initiation Portend Flares in Systemic Lupus Erythematosus: A Post-Hoc Analysis of Three Phase III Clinical Trials of Belimumab

“…However, early identification of patients at risk for subsequent flares upon commencement of belimumab treatment remains a challenge, leaving an area of uncertainty during the critical stages of early follow-up. This need was recently exemplified in a report of de novo lupus nephritis cases after initiation of belimumab therapy ( 22 ).…”

Belimumab for systemic lupus erythematosus – Focus on lupus nephritis

“…(3 de-novo LN out of 66 patients without prior LN; and 2 LN flares among 29 patients with known LN). 102 …”

“…treated with BEL Riancho-Zarrabeitia L 106 2020 retrospective analysis 1/11 HCQ (all) MMF, AZA, CYC, LEF (several) 1 case of de novo LN in a cohort of 11 SLE pts. treated with BEL for musculoskeletal and/or cutaneous manifestations Hassan S 107 2020 prospective observational study 2/14 SoC study with secondary non-responders to RTX in SLE, details see Table 4 1 patient relapsed with LN class III during BEL treatment, another developed de novo LN class V; both were then treated with CYC Parodis I 102 2020 prospective observational study 6/66 de novo 2/29 flare SoC 6 out of 66 SLE pts. with no prior history of LN developed biopsy-proven LN during BEL treatment (after a median of 7.4 m); 2 out of 66 control pts.…”

What's New in the Treatment of Systemic Lupus Erythematosus

“…Of notice, both these patients improved immediately by withdrawal of belimumab and before the initiation of standard therapy. Furthermore, a retrospective study recently reported that introducing belimumab into a standard treatment regimen of patients with lupus without nephritis resulted in development of lupus nephritis with an increased frequency compared to a control group of patients with lupus (hazard ratio, HR: 10.7; p = 0.012) (27). The authors proposed that concomitant treatment with antimalarials was protective over this "nephritogenic" potential of belimumab (HR: 0.2; p = 0.046).…”