Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles
| Autor: | Peter Colman, Chris Chamberlain, Geoffrey I Johnston, Falk Hiepe, Ann Ranger, C. Stach, Thomas Dörner, Linda C. Burkly, Murray B. Urowitz, Miren Zamacona, Christian Otoul |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Adolescent Anti-nuclear antibody CD40 Ligand Immunology Placebo Severity of Illness Index Gastroenterology Drug Administration Schedule General Biochemistry Genetics and Molecular Biology Polyethylene Glycols Immunoglobulin Fab Fragments Young Adult 03 medical and health sciences 0302 clinical medicine Double-Blind Method Rheumatology Internal medicine medicine Humans Immunologic Factors Lupus Erythematosus Systemic Immunology and Allergy Adverse effect Aged Whole blood 030203 arthritis & rheumatology Autoimmune disease Systemic lupus erythematosus Dose-Response Relationship Drug business.industry Autoantibody Middle Aged medicine.disease Regimen Treatment Outcome 030104 developmental biology RNA Administration Intravenous Female Transcriptome business |
| Zdroj: | Annals of the Rheumatic Diseases. 76:1837-1844 |
| ISSN: | 1468-2060 0003-4967 0176-4594 |
| DOI: | 10.1136/annrheumdis-2017-211388 |
| Popis: | ObjectivesSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40–CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE.MethodsThis 32-week randomised, double-blind, multicentre study (NCT01764594) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable). Sixteen patients were randomised to 30 mg/kg dapirolizumab pegol followed by 15 mg/kg every 2 weeks for 10 weeks; eight patients received a matched placebo regimen. Randomisation was stratified by evidence of antiphospholipid antibodies. Patients were followed for 18 weeks after the final dose.ResultsNo serious treatment-emergent adverse events, thromboembolic events or deaths occurred. Adverse events were mild or moderate, transient and resolved without intervention. One patient withdrew due to infection.Efficacy assessments were conducted only in patients with high disease activity at baseline. Five of 11 (46%) dapirolizumab pegol-treated patients achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment response (vs 1/7; 14% placebo) and 5/12 (42%) evaluable for SLE Responder Index-4 responded by week 12 (vs 1/7; 14% placebo). Mechanism-related gene expression changes were observed in blood RNA samples.ConclusionsDapirolizumab pegol could be an effective biological treatment for SLE. Further studies are required to address efficacy and safety.Trial registration numberNCT01764594. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|