Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus

Clin Exp Immunol. 2016 Feb;183(2):258-70. doi: 10.1111/cei.12705. Epub 2015 Nov 9.


This study's objective was to assess the effects of PD-0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony-stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD-0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre- and post-treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14(+) CD16(+) monocytes, urinary N-terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater-than-dose-proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14(+) CD16(+) cells, uNTX, ALT, AST and CK levels at most time-points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between-group differences were seen in CLASI. Patients receiving PD-0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD-0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end-points.

Trial registration: NCT01470313.

Keywords: CD14/CD16 monocytes; cutaneous lupus erythematosus; immunohistochemistry; macrophage colony-stimulating factor; osteoclasts.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Aspartate Aminotransferases / urine
  • Collagen / urine
  • Creatine Kinase / urine
  • Double-Blind Method
  • Female
  • Histiocytes / drug effects
  • Histiocytes / pathology
  • Humans
  • Immunohistochemistry
  • Immunotherapy
  • Lipopolysaccharide Receptors / immunology
  • Lupus Erythematosus, Cutaneous / drug therapy*
  • Lupus Erythematosus, Cutaneous / immunology*
  • Macrophage Colony-Stimulating Factor / immunology*
  • Macrophages / immunology*
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Receptors, IgG / immunology
  • Severity of Illness Index
  • Skin / drug effects
  • Skin / pathology
  • Young Adult


  • Antibodies, Monoclonal
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • urinary N-telopeptide of type I collagen, human
  • Macrophage Colony-Stimulating Factor
  • Collagen
  • Aspartate Aminotransferases
  • Creatine Kinase

Associated data