De novo lupus nephritis during treatment with belimumab

Rheumatology (Oxford). 2021 Sep 1;60(9):4348-4354. doi: 10.1093/rheumatology/keaa796.


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.

Keywords: LN; SLE; adverse events; autoantibodies; belimumab; biologic agents; complement; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Autoantibodies / immunology
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Nephritis / diagnosis*
  • Lupus Nephritis / immunology
  • Male
  • Middle Aged


  • Antibodies, Monoclonal, Humanized
  • Autoantibodies
  • Immunosuppressive Agents
  • belimumab