Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia

Margaret V. Ragni; Rachel C. Jankowitz; Kristen Jaworski; Elizabeth P. Merricks; Mark T. Kloos; Timothy C. Nichols

doi:10.1160/TH11-04-0274

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(04): 641-645
DOI: 10.1160/TH11-04-0274

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia^[*]

Margaret V. Ragni

¹Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

²Hemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA

,

Rachel C. Jankowitz

¹Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

,

Kristen Jaworski

²Hemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA

,

Elizabeth P. Merricks

³Department of Pathology and Laboratory Medicine/ Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, North Carolina, USA

,

Mark T. Kloos

³Department of Pathology and Laboratory Medicine/ Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, North Carolina, USA

,

Timothy C. Nichols

³Department of Pathology and Laboratory Medicine/ Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, North Carolina, USA

› Author Affiliations

Abstract

Summary

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.

Keywords

Clinical trial - interleukin-11 - menorrhagia - von Willebrand disease - women

Full Text

References

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Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia[*]

Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia^[*]