Haematologica 2000;85:supplement to no. 10 - Supplements ...
Haematologica 2000;85:supplement to no. 10 - Supplements ...
Haematologica 2000;85:supplement to no. 10 - Supplements ...
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4<br />
J.M. Lusher<br />
(range 1-34) for patients with high titer (≥ 5 BU)<br />
inhibi<strong>to</strong>rs. In all patients, the median number of<br />
ED at the time of interim data analysis was 55. 12<br />
The PUP (and, Minimally Treated Patient) Trial with<br />
a Second Generation rFVIII Concentrate Formulated<br />
with Sucrose Rather than Albumin (Kogenate ® FS)<br />
From Oc<strong>to</strong>ber, 1997 until April 30, 1999, 62<br />
infants and young children with severe hemophilia<br />
A (< 2% FVIII) were enrolled in a prospective,<br />
multicenter, multinational safety and efficacy<br />
study of a second generation rFVIII concentrate<br />
which is formulated with sucrose rather<br />
than human serum albumin (rFVIII-FS;<br />
Kogenate ® FS). The 62 study subjects included 38<br />
PUPs and 24 minimally treated patients (MTPs)<br />
with < 4 ED <strong>to</strong> rFVIII (one MTP received a plasma-derived<br />
FVIII concentrate, while the other 23<br />
MTPs had received only rFVIII). All had negative<br />
inhibi<strong>to</strong>r assays (Nijmegen modification 13 of the<br />
Bethesda assay) at study entry. Once on study, all<br />
patients received only rFVIII-FS, for treatment of<br />
bleeding or for prophylaxis. Inhibi<strong>to</strong>r assays were<br />
performed every 3-4 ED for the first 20 ED or<br />
every 3 months (whichever came first); every <strong>10</strong><br />
ED from 21-50 ED or every 3 months (whichever<br />
came first); and every 3 months thereafter. As<br />
of August, 1999, 61 of 62 study subjects had<br />
been treated with rFVIII-FS, and 8 had developed<br />
an inhibi<strong>to</strong>r after 2-15 ED (median 7 ED).<br />
Among 5 American patients who developed<br />
inhibi<strong>to</strong>rs, 2 were African-American children (of<br />
5 African-Americans in the study). Of the 8<br />
inhibi<strong>to</strong>r patients, 5 (all American patients) were<br />
high titer (16, 23, <strong>10</strong>9, 249, and 271 BU) while<br />
3 (all European) were low titer (1.25, 1.9, and<br />
4.0 BU). However, many of the subjects in this<br />
cohort are still at risk for inhibi<strong>to</strong>r development,<br />
having had relatively few ED (29 still had < <strong>10</strong><br />
ED). 14<br />
Prospective clinical trials with rFVIII preparations<br />
in previously treated patients<br />
Prospective clinical trials have been conducted<br />
in previously treated patients (PTPs) with the<br />
two full-length rFVIII preparations (Kogenate ®<br />
and Recombinate ® ), and with the B-domain<br />
deleted rFVIII (ReFac<strong>to</strong> ® ). 15-18<br />
In the PTP trial with Kogenate ® , 58 patients<br />
received Kogenate ® exclusively in an international,<br />
multicenter, prospective study of more<br />
than 5 years duration. Fifty-four of the 58 subjects<br />
had severe hemophilia A (