Objectives Systemic 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.
Methods This 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.
Results No 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.
Conclusions Dapirolizumab pegol could be an effective biological treatment for SLE. Further studies are required to address efficacy and safety.
Trial registration number NCT01764594.
- autoimmune disease
- systemic lupus erythematosus
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Handling editor Tore K Kvien
Contributors CC, AMR, LCB and MZ contributed to the conception and design of the study; CC, TD, FH, GIJ, CO and MU were involved in the acquisition of data; CC, AMR, PJC, TD, FH, GIJ, CO, CS, MU, LCB and MZ contributed to the analysis and interpretation of data. All authors contributed to drafting and/or revising the manuscript.
Funding UCB Pharma and Biogen.
Competing interests CC, PJC, GIJ, CO and MZ are full-time employees of UCB Pharma and hold stock awards and/or options. CS is a full-time employee of UCB Biosciences GmbH and holds stock awards and/or options. AMR was a full-time employee and stock holder of Biogen at the time the study was conducted. LCB is a full time employee and stockholder of Biogen. FH has received consultancy fees from UCB, Sanofi, Eli Lilly, Baxter, BMS and research grants from Deutsche Forschungsgemeinschaft, IMI (PRECISESADS) and attended speakers’ bureau for GSK, Roche Pharma and Pfizer. TD has received consultancy fees and research grants from UCB, Biogen, Roche, Sanofi, Eli Lilly, Jansen and research grants from Deutsche Forschungsgemeinschaft and EU Horizon 2020 (Harmonics). MU has served as Chair of the Data and Safety Monitoring Committee for the study.
Patient consent A patient consent form was completed.
Ethics approval This was a national, regional, Independent Ethics Committee or Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.