Konrad van der Zwet, Allert H. Vos, Marjon H. Cnossen, Floor Heubel-Moenen, Saskia E.M. Schols, Paula F. Ypma, Paul L. den Exter, Hélène L. Hooimeijer, Michiel Coppens, Ron A. A. Mathôt, Alexander Janßen, Anouk A. M. T. Donners, Ilmar C. Kruis, Rolf T. Urbanus, Lize F. D. van Vulpen, Corien L. Eckhardt, Roger E. G. Schutgens, Kathelijn Fischer, Marjon H. Cnossen, Frank W.G. Leebeek, Ron A. A. Mathôt, Karin Fijnvandraat, Michiel Coppens, Karina Meijer, Marieke J. H. A. Kruip, Suzanne Polinder, J. Lock, H.C.A.M. Hazendonk, Iris van Moort, Jessica M. Heijdra, M.C.H.J. Goedhart, Wala Al Arashi, Tim Preijers, Nico C. B. de Jager, Laura H. Bukkems, Michael E. Cloesmeijer, Alexander Janßen, R. Y. J. Tamminga, Paul Brons, Saskia E.M. Schols, Jeroen Eikenboom, F.J.M. van der Meer, Roger E. G. Schutgens, Kathelijn Fischer, Karin P. M. van Galen, Erik E.A.M. Beckers, Floor C.J.I. Heubel-Moenen, Laurens Nieuwenhuizen, Paula F. Ypma, M.H.E. Driessens, Ineke van Vliet, Peter W. Collins, Ri Liesner, Pratima Chowdary, Carolyn M. Millar, Dan Hart, David Keeling
BACKGROUND: Emicizumab provides effective prophylaxis for hemophilia A (HA), but its cost puts a burden on health care systems. Pharmacokinetic (PK)-pharmacodynamic analyses suggest that emicizumab is effective at lower trough concentrations (Ctrough) than the mean 55 μg/mL reported with conventional dosing. OBJECTIVES: To perform an interim analysis comparing bleeding control during 6 months of conventional emicizumab dosing vs PK-guided dosing in participants with HA, targeting a Ctrough of 25-35 μg/mL. METHODS: The DosEmi study (NCT06320626) is an ongoing multicenter, open-label, crossover Dutch trial. Eligible participants were aged ≥16 years using emicizumab for ≥12 months with good bleeding control (≤2 treated bleeds/6 months, none spontaneous). This planned interim analysis compared 6 months' bleeding on conventional dosing with PK-guided dosing. Study continuation criteria were ≤15% decrease in the proportion of participants without treated bleeds, maximum of 2 spontaneous bleeds overall, and <1.0 increase in bleeds/y (annualized bleeding rate). RESULTS: In 26 participants with severe HA, PK-guided dosing reduced emicizumab consumption by 39% (range, 13%-50%). The proportion of participants without treated bleeds was 69% with conventional dosing vs 58% with PK-guided dosing (risk difference, +11%; P = .254); the proportion without joint bleeds remained stable at 85% vs 88%, respectively (risk difference, -4%; P = .500). The annualized bleeding rate remained low (0.7 vs 0.9; P = .132), including 1 spontaneous muscle bleed (emicizumab concentration 52.5 μg/mL). CONCLUSION: These interim results suggest that bleeding control with PK-guided reduced emicizumab dosing (target Ctrough 25-35 μg/mL) is similar to conventional dosing. All prespecified criteria for study continuation and inclusion of participants aged <16 years were met.