title: Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia.
abstract: Lack of effective treatment for menorrhagia is the greatest unmet healthcare need in women with von Willebrand disease (VWD). We conducted a single-centre phase II clinical trial to determine efficacy and safety of recombinant IL-11 (rhIL-11, Neumega®) given subcutaneously for up to seven days during six consecutive menstrual cycles each in seven women with mild VWD and menorrhagia refractory to haemostatic or hormonal agents. rhIL-11 reduced menstrual bleeding severity as measured by pictorial blood assessment chart (PBAC) ≥ 50% (to <100) in 71% of subjects, cycle severity ≥ 50% in 71%, and bleeding duration ≥ 2 days in 85%, all p ≤ 0.01. After rhIL-11, plasma VWF:RCo increased 1.1-fold, but did not correlate with PBAC, r=0.116, bleeding duration, r=0.318, or cycle severity, r=-0.295, or hsCRP, r=-0.003, all p>0.05. Platelet VWF mRNA expression by quantitative PCR increased mean four-fold (1.0-13.5). rhIL-11 was well tolerated with grade 1 or less fluid retention, flushing, conjunctival erythema, and local bruising. In summary, rhIL-11 reduces menorrhagia safely and warrants further study.
authors.affiliation: Division Hematology/Oncology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. ragni@dom.pitt.edu
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Jankowitz
authors.forename: Kristen
authors.initials: K
authors.lastname: Jaworski
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: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004351:Drug Resistance; D004890:Erythema / Q000209:etiology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D017370:Interleukin-11 / Q000008:administration & dosage* / Q000009:adverse effects; D008595:Menorrhagia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D016387:Women's Health / Q000639:trends; D014842:von Willebrand Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D017370:Interleukin-11; D011994:Recombinant Proteins; D014841:von Willebrand Factor