Development of anti-velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease.
Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies. Sixty-four patients were treatment-naïve at baseline and 225 patients were switched to velaglucerase alfa from imiglucerase treatment. They received velaglucerase alfa treatment for a median of 36.4weeks (interquartile range 26.4-155.4weeks). Four patients (1.4%) became positive for anti-velaglucerase alfa IgG antibodies, two of whom had antibodies that were neutralizing in vitro, but there were no apparent changes in patients' platelet counts, hemoglobin levels or levels of CCL18 and chitotriosidase, suggestive of clinical deterioration after anti-velaglucerase alfa antibodies were detected, and no infusion-related adverse events were reported. Less than 2% of patients exposed to velaglucerase alfa tested positive for antibodies and there was no apparent correlation between anti-velaglucerase alfa antibodies and adverse events or pharmacodynamic or clinical responses.
Mater Misericordiae University Hospital, Dublin, Ireland. Electronic address: gpastores@mater.ie.
Gregory M
GM
Pastores
La Rabta Hospital, Tunis, Tunisia. Electronic address: hadhami.baili@laposte.net.
Hadhami Ben
HB
Turkia
Sanatorio Español, Asunción, Paraguay. Electronic address: gderlis@conexion.com.py.
Derlis E
DE
Gonzalez
The Jikei University School of Medicine, Tokyo, Japan. Electronic address: hiroy@jikei.ac.jp.
Hiroyuki
H
Ida
Ain Shams University Hospital, Cairo, Egypt. Electronic address: azazaghloul@yahoo.com.
Azza A G
AA
Tantawy
Shire, Lexington, MA, USA. Electronic address: yqin@shire.com.
Yulin
Y
Qin
Shire, Lexington, MA, USA. Electronic address: yqiu@shire.com.
Yongchang
Y
Qiu
Shire, Lexington, MA, USA. Electronic address: qdinh@shire.com.
Quinn
Q
Dinh
Shaare Zedek Medical Center, Hebrew University-Hadassah Medical School, Jerusalem, Israel. Electronic address: azimran@gmail.com.
Ari
A
Zimran
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D000917:Antibody Formation; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000906:Antibodies; D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human
Antibodies; Enzyme replacement therapy; Gaucher disease; Seroconversion; Velaglucerase alfa