Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A

• Published in: Thrombosis and haemostasis Vol. 109; no. 2; p. 248
• Main Authors: Ragni, Margaret V, Novelli, Enrico M, Murshed, Anila, Merricks, Elizabeth P, Kloos, Mark T, Nichols, Timothy C
• Format: Journal Article
• Language: English
• Published: Germany 01.02.2013
• Subjects: Adult; Biomarkers - blood; Deamino Arginine Vasopressin - adverse effects; Deamino Arginine Vasopressin - therapeutic use; Drug Resistance; Factor VIII - metabolism; Female; Hemophilia A - blood; Hemophilia A - diagnosis; Hemophilia A - drug therapy; Hemostatics - adverse effects; Hemostatics - therapeutic use; Humans; Interleukin-11 - adverse effects; Interleukin-11 - therapeutic use; Male; Middle Aged; Pennsylvania; Prospective Studies; Protein Multimerization; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - blood; Severity of Illness Index; Time Factors; Treatment Outcome; von Willebrand Diseases - blood; von Willebrand Diseases - diagnosis; von Willebrand Diseases - drug therapy; von Willebrand Diseases - genetics; von Willebrand Factor - genetics; von Willebrand Factor - metabolism; Young Adult
• ISSN: 2567-689X
• DOI: 10.1160/TH12-06-0447

Desmopressin (DDAVP) is the treatment of choice in those with mild von Willebrand disease (VWD), yet 20% are unresponsive to DDAVP, and among the 80% who respond, the response is transient, as endothelial stores are depleted after three days. We, therefore, conducted a single-center Phase II clinical trial to determine safety and biologic efficacy of recombinant interleukin-11 (rhIL-11, Neumega®) in patients with VWD unresponsive or allergic to DDAVP, or mild or moderate haemophilia A (HA). Increases in VWF:RCo wer e observed by 48 hours after rhIL-11, with a 1.54-fold increase by Day 4, 1.30-fold in VWD and 1.73-fold in HA. Similarly, by 48 hours, increases in VIII:C were observed, with a 1.65-fold increase by Day 4, 1.86-fold in VWD and 1.48-fold in HA. Platelet VWFmRNA expression by qPCR increased 0.81-fold but did not correlate with plasma VWF:Ag responses. rhIL-11 was well tolerated, with grade 1 or less fluid retention, flushing, conjunctival erythema, except for transient grade 3 hyponatraemia in one subject after excess fluid intake for diabetic hyperglycaemia, which resolved with fluid restriction. In summary, rhIL-11 increases VWF levels in two of four DDAVP-unresponsive or allergic VWD and F.VIII levels in four of five mild or moderate haemophilia A subjects, suggesting its potential use in treatment of these disorders.