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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
| Content Provider | Oxford Academic |
|---|---|
| Author | Masek-Hammerman, K Peeva, E Ahmad, A Menon, S Afsharvand, M Peng Qu, R Cheng, J B Syed, J Zhan, Y O'Neil, S P Pleasic-Williams, S Cox, L A Beidler, D |
| Copyright Year | 2016 |
| Abstract | 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. |
| Related Links | https://academic.oup.com/cei/article-pdf/183/2/258/41126121/cei12705.pdf |
| Ending Page | 270 |
| Starting Page | 258 |
| File Format | |
| ISSN | 00099104 |
| e-ISSN | 13652249 |
| DOI | 10.1111/cei.12705 |
| Journal | Clinical and Experimental Immunology |
| Issue Number | 2 |
| Volume Number | 183 |
| Language | English |
| Publisher | Oxford Academic |
| Publisher Date | 2016-01-13 |
| Access Restriction | Open |
| Subject Keyword | Clinical Medicine Immunology Medicine and Health Pathology Immunohistochemistry Cd14 Antigen Monoclonal Antibodies Histiocytes Lupus Erythematosus, Cutaneous Macrophage Colony-stimulating Factor Monocytes Skin Lesion Antigens, Cd16 Pharmacokinetics Pharmacodynamics Macrophages Urinary Tract Treatment Outcome Cd14/cd16 Monocytes Cutaneous Lupus Erythematosus Osteoclasts |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
