title: Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology and Vascular Medicine Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. ragni@dom.pitt.edu
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Novelli
authors.forename: Anila
authors.initials: A
authors.lastname: Murshed
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Merricks
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kloos
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Nichols
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003894:Deamino Arginine Vasopressin / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D017370:Interleukin-11 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania; D011446:Prospective Studies; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D014842:von Willebrand Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006490:Hemostatics; D017370:Interleukin-11; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin; C105308:oprelvekin