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Abstract: SA-PO279

Prospective Evaluation of an Improved Eculizumab Initial Phase Dosing Regimen in Adult Patients with Atypical Hemolytic Uremic Syndrome

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • ter Avest, Mendy, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Bouwmeester, Romy N., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Duineveld, Caroline, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Van den heuvel, Lambertus P.W.J., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Wetzels, Jack F., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Van De Kar, Nicole, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Ter heine, Rob, Radboudumc, Nijmegen, Gelderland, Netherlands

Group or Team Name

  • The CUREiHUS Study Group.
Background

Complete complement inhibition is often not achieved after the first dose of eculizumab due to subtherapeutic eculizumab concentrations (<50mg/L), while adequate complement inhibition is critical to prevent irreversible organ damage in aHUS. In this study we prospectively evaluated an improved initial phase dosing regimen.

Methods

The new regimen consisted of a weight-based loading dose on day 1 (>120kg: 2400mg; 90-120kg: 2100mg; 60-90kg: 1800mg; 40-60kg: 1500mg), followed by the standard biweekly 1200mg from day 15 onward. Eculizumab concentrations were measured to monitor therapy and compared with a historical cohort that received the standard dose. At each timepoint (day 7, 14, 28), we calculated the geometric mean eculizumab trough concentration and the fraction of patients with a subtherapeutic eculizumab concentration (<50mg/L) for both groups.

Results

15 patients receiving the new dosing regimen and 22 patients receiving standard dose were evaluated. Baseline characteristics were similar across the groups. The eculizumab concentrations and the geometric mean concentrations on day 7, 14 and 28 are shown in Figure 1. Eculizumab concentrations were subtherapeutic in 42% (8/19), 0% (0/21) and 0% (0/16) of the patients on day 7, 14 and 28 respectively (standard dose) and in 0 (0/12), 20% (2/10) and 12.5% (1/8) of the patients on day 7, 14, and 28 respectively (new dose).

Conclusion

We prospectively confirmed improved early target attainment of a weight-based loading dose of eculizumab on day 1 followed by the maintenance phase dose from day 15 onward.

Eculizumab concentrations for standard (black) and new initial phase (grey). Horizontal lines represents the geometric mean concentration. The dotted line represents an eculizumab concentration of 50 mg/L (threshold for complete C5 inhibition).

Funding

  • Government Support – Non-U.S.