Figure 4.
Simulation of optimal dosing algorithms for nonbleeding patients with TA-TMA. The y-axis shows the probability of target attainment determined as the proportion of patients who achieved eculizumab concentrations above the target, and the y-axis shows each body weight cohort. A total of 12 000 age-body weight–matched subjects was randomly sampled from the CDC-NHANES database. Six body weight cohorts were defined as follows: <10 kg, 10 to <20 kg, 20 to <30 kg, 30 to <40 kg, 40 to <70, and 70 to <100 kg. Realistic predose sC5b-9 levels were generated by simulation, to be matched to the observed sC5b-9 distribution. A Monte Carlo Simulation analysis was conducted to predict eculizumab trough concentrations for each dosing scenario according to NONMEM. The original dose used for protocols 1 and 3 is the current dose amount (in milligrams) by weight group approved for aHUS, but administered in intensified dose intervals. Protocols 2 and 4 evaluated the optimal dose (in milligrams) that achieved 80% target attainment considering a dosage strength of 300 mg per vial.