Hospital Pharmacy - December 2017 - 727

737135
research-article2017

HPXXXX10.1177/0018578717737135Hospital PharmacyVan Rossum and Holsopple

Letter to the Editor

Response to Letter to the Editor on
"Enzyme Replacement or Substrate
Reduction? A Review of Gaucher
Disease Treatment Options"

Hospital Pharmacy
2017, Vol. 52(11) 727-728
© The Author(s) 2017
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https://doi.org/10.1177/0018578717737135
DOI: 10.1177/0018578717737135
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Alison Van Rossum1 and Megan Holsopple2
We appreciate the comments by Ibrahim and Call on our article "Enzyme Replacement or Substrate Reduction? A Review
of Gaucher Disease Treatment Options," particularly regarding information published since our article was originally
written such as the extension study of the ENCORE trial.
In the ENCORE extension study, 147 patients with
Gaucher disease type 1 were either continued on eliglustat
(received up to 4.5 years of eliglustat therapy) or transitioned
from imiglucerase to eliglustat (received 2 years of eliglustat
therapy). At the end of the study, ≥85% of patients maintained stable hematologic and organ volume values compared with baseline (pre-eliglustat) values. Adverse events
were recorded in 94% of patients; the majority of the reported
adverse events were considered mild (74%), and 8% of
patients withdrew due to treatment-related adverse effects.1
The ENGAGE trial was originally excluded because the
authors chose to emphasize trials with an active comparator
when possible. However, it is helpful to note that the
ENGAGE trial demonstrated in 40 treatment-naive patients
with Gaucher disease type 1 that eliglustat reduced spleen
volume by 27.77% after 9 months of therapy while spleen
volume increased by 2.26% at 9 months in the placebo group
(difference of −30.03%; 95% confidence interval, -36.82%
to −23.24%; P < 0.001).2 Similarly, a small trial evaluating
miglustat in treatment-naive patients was not included in the
initial article. In the observational trial of 26 patients with
Gaucher disease type 1, 10 of whom were treatment-naive,
miglustat showed significant changes from baseline in treatment-naive patients in total cholesterol (7% increase; P =
0.05), high-density lipoprotein cholesterol (24% increase; P
= 0.005), triglycerides (20% decrease; P = 0.05), C-reactive
protein (32% decrease; P = 0.05), and chitotriosidase (39%
decrease; P = 0.03) after 36 months of therapy. Other markers of Gaucher disease severity were not measured, and
adverse effects were not discussed extensively.3
Regarding the note on antibody development, Ibrahim
and Call are correct in stating there are no head-to-head trials
between the enzyme replacement therapies and antibody
development. In the initial article, we referred to the reported
rates of antibody development to each of the agents.
Currently, some published data report the rate of immunoglobulin G (IgG) antibody development to imiglucerase as

15%, IgG antibody development to taliglucerase as 6%, and
IgG antibody development to velaglucerase as 1.4%.4-6
However, it is important to note that different resources will
likely report different rates of antibody development and
rates may not be directly comparable. In addition, as with
any biological therapy, immunogenicity is a concern, and
providers should monitor patients for signs and symptoms of
immunologic responses.
We additionally acknowledge that reports of imiglucerase
use in pregnancy women indicate imiglucerase may be a safe
option for Gaucher disease treatment during pregnancy and
may decrease the risk of complications in these patients during pregnancy.7 Similarly, reports and clinical experience
suggest velaglucerase and taliglucerase may be safely used
to treat Gaucher disease during pregnancy.7,8 However, while
clinical experience with enzyme replacement therapy suggests these agents may be safe to use in pregnancy, enzyme
replacement therapies, like most medications, have not been
evaluated in pregnant women with adequate, well-controlled
trials; therefore, safety cannot be guaranteed in this population. As noted in the original article, because imiglucerase
has been on the market longest and thus has the longest history of clinical use, it may be a safer option than the newer
enzyme replacement therapies.
Regarding the note on Canadian and European indications for taliglucerase and imiglucerase, the intent of our
article was to address indications approved by Food and
Drug Administration (FDA) for use in the United States.
Of note, while the official indication approved by FDA for
all 3 enzyme replacement therapies specifically states they
are indicated for use in Gaucher disease type 1, FDAdesignated imiglucerase as an orphan drug for Gaucher
disease types 1, 2, and 3 and taliglucerase and velaglucerase have an orphan drug designation for Gaucher disease without specifying type.4,9-11 We encourage readers
1

University of Florida Health Jacksonville, FL, USA
Froedtert & the Medical College of Wisconsin, Milwaukee, WI, USA

2

Corresponding Author:
Alison Van Rossum, University of Florida Health Jacksonville,
655 W 8th Street, Jacksonville, FL 32209, USA.
Email: alison.vanrossum@jax.uf.edu
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