Factor VIII concentrate dosing with lean body mass, ideal body weight and total body weight in overweight and obesity: A randomized, controlled, open‐label, 3 × 3 crossover trial. Issue 3 (22nd March 2021)

• Record Type: Journal Article
• Authors: Seaman, Craig D.; Yabes, Jonathan G.; Lalama, Christina M.; Ragni, Margaret V.
• Is Part Of: Haemophilia. Volume 27:Issue 3(2021)
• Page Start: 351
• Page End: 357
• Publication Date: 2021-03-22
• Subjects: clotting factor -- factor VIII -- haemophilia A -- obesity -- pharmacokinetics; Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.14285
• Languages: English
• ISSNs: 1351-8216

Abstract

Abstract: Introduction: Obesity alters the pharmacokinetic (PK) properties of drugs making it difficult to determine the appropriate dose when administering weight‐based medications. Alternative descriptors of body weight, such as lean body mass (LBM) and ideal body weight (IBW), are sometimes used in these situations. Methods: We performed a single‐centre, randomized, controlled, open‐label, 3 × 3 crossover trial to determine whether recombinant factor VIII (rFVIII) dosing based on LBM and IBW achieves a targeted FVIII recovery with better precision than based on total body weight (TBW) in overweight and obese, adult males with haemophilia A. Participants were randomized to 1 of 6 possible FVIII concentrate dosing sequence scenarios (TBW, LBM and IBW). Recombinant FVIII was administered on 3 separate weeks following a washout period of at least 72 hours. Results: A total of 19 participants were randomized and completed the study. FVIII recovery was lower at 30 minutes post‐rFVIII infusion in LBM vs TBW and IBW vs TBW‐based dosing, mean difference −0.38 (95% CI: −0.56, −0.20) and −0.28 (95% CI: −0.47, −0.10) IU/dL per IU/kg, respectively. In LBM vs TBW and IBW vs TBW‐based dosing, there was a non‐significant increase in the proportion of participants with a targeted FVIII recovery of 2.00 ± 0.20 IU/dl per IU/kg, OR = 1.93 (95% CI: 0.44, 8.55) and OR = 3.65 (0.80, 16.72), respectively. Discussion: Based on our study's findings, overweight and obese patients with haemophilia A may benefit from an individualized PK analysis using LBM and IBW to determine the most accurate, and potentially cost‐effective, method of achieving targeted FVIII recovery.