General
Information
This
information is for reference only and is not a treatment
recommendation. Safety and efficacy of ixekizumab in patients with
diabetes is undetermined because Lilly has not conducted
studies of ixekizumab in this specific patient population. Decisions
regarding the use of ixekizumab in patients with diabetes should be
made at the discretion of the prescribing physician using their best
clinical judgment.
Diabetes
or elevated fasting serum glucose are not listed as adverse drug
reactions in the Taltz Summary of Product Characteristics.1
Glucose
Related TEAEs in Psoriasis Trials
Fasting
serum glucose TEAEs were evaluated in the UNCOVER clinical trials
during the double-blind treatment period through week 12 (including
2328 patients treated with ixekizumab 80 mg Q4W or Q2W and 791
patients treated with placebo) and through week 60.2
As shown in Figure 1,
ixekizumab was not associated with abnormal glucose levels at 12 and
60 weeks.3 It
should be noted that the patients in this group were not exclusively
patients with diabetes.
Figure
1. Percentage of Patients With Abnormal High Fasting Glucose Values
at Week 12 (UNCOVER-1, -2, and -3) and Week 60 (UNCOVER-1 and -2)3
Abbreviations:
ETN = etanercept 50 mg twice weekly; IXE Q2W = ixekizumab 80 mg every
2 weeks; IXE Q4W = ixekizumab 80 mg every 4 weeks; PBO = placebo.
aDefinition
of abnormal high values varied according to age, gender, and race of
patient. Ranges for fasting glucose were 66-365 mg/dL.
Fasting
glucose measured at week 60 was comparable in patients treated with
ixekizumab and those receiving placebo during the maintenance period
(weeks 12-60 of UNCOVER-1 and -2). See Table
1.
Table
1. Fasting Glucose Levels Through Week 12 and Through Week 60 of
UNCOVER Clinical Trials in Psoriasis4
|
Week
12 (Induction Periods of UNCOVER-1, -2, and -3)
|
Week
12 (Induction Periods of UNCOVER-1, -2, and -3)
|
Week
12 (Induction Periods of UNCOVER-1, -2, and -3)
|
Week
60 (Maintenance Period of UNCOVER-1 and -2)
|
Week
60 (Maintenance Period of UNCOVER-1 and -2)
|
Fasting
glucose level, mg/dL
|
PBO
N=791
|
IXE
Q4W
N=1161
|
IXE
Q2W
N=1167
|
PBO
N=402
|
IXE
Q4W
N=416
|
Mean
Baseline (SD)
|
103
(32)
|
102
(31)
|
101
(29)
|
100
(21)
|
101
(26)
|
Mean
Change from Baseline (SD)
|
1.1
(27)
|
1.7
(23)
|
0.8
(22)
|
0.7
(14)
|
0.4
(21)
|
Abbreviations:
IXE Q2W = ixekizumab 80 mg every 2 weeks; IXE Q4W = ixekizumab 80 mg
every 4 weeks; PBO = placebo.
Ixekizumab
treatment was not associated with clinically meaningful adverse
changes of cardiovascular risk factors, including blood pressure,
glucose control, or proatherogenic components of the lipid panel in
the overall population during the induction (through week 12) and
maintenance periods (through week 60).5
However, these analyses were not conducted specifically in patients
with diabetes.
Note:
The dosing schedule IXEQ4W during the first 12 weeks of treatment
(induction phase) is not consistent with the approved dosing schedule
for plaque psoriasis in the Taltz summary of product characteristics.
Please refer to the Taltz summary of product characteristics for
approved dosing. 1
Glucose
Related TEAEs in Psoriatic Arthritis Trials
Fasting
serum glucose TEAEs were evaluated in the SPIRIT-P1 and SPIRIT-P2
trials during the double-blind treatment period through week 24,
including 454 patients treated with ixekizumab 80 mg Q4W or Q2W and
224 patients treated with placebo.6
In
the integrated 24-week placebo-controlled treatment periods of
SPIRIT-P1 and SPIRIT-P2, treatment-emergent high fasting serum
glucose (defined as a change from a fasting serum glucose value less
than or equal to the ULN at baseline, to a value more than the ULN at
any time during the treatment period) was reported in 3.8% of
patients treated with ixekizumab 80 mg Q2W and 1.0% of patients
treated with ixekizumab 80 mg Q4W compared with 3.8% of patients in
the placebo group. It should be noted that these analyses were not
conducted specifically in patients with diabetes.6
After
24 weeks, ixekizumab treatment compared with placebo was not
associated with clinically meaningful adverse changes of CV risk
factors in patients with PsA, including blood pressure, body weight,
glucose control, or proatherogenic components of the lipid panel.6
However, these analyses were not conducted exclusively in patients
with diabetes.
Note: The
dosing schedule IXEQ2W is not consistent with the approved dosing
schedule for psoriatic arthritis in the Taltz summary of product
characteristics. Please refer to the Taltz summary of product
characteristics for approved dosing.1
Glucose
Related TEAEs in Axial Spondyloarthritis Trials
AS/r-axSpA
Trials
Fasting
serum glucose TEAEs were evaluated in the COAST-V and COAST-W trials
during the double-blind treatment period through week 16, including
376 patients treated with ixekizumab 80 mg Q4W or Q2W and 191
patients treated with placebo.7,8
In
the integrated 16-week placebo-controlled treatment periods of
COAST-V and COAST-W, treatment-emergent high fasting serum glucose
(defined as a change from a fasting serum glucose value less than or
equal to the ULN at baseline, to a value more than the ULN at any
time during the treatment period) was reported in 12.6% of patients
treated with ixekizumab 80 mg Q2W and 15.4% of patients treated with
ixekizumab 80 mg Q4W compared with 9.9% of patients in the placebo
group. It should be noted that these analyses were not conducted
specifically in patients with diabetes.6
Non-radiographic
Axial Spondyloarthritis Trials
Fasting
serum glucose TEAEs were evaluated in the COAST-X trial during the
double-blind treatment period through week 52, including 198 patients
treated with ixekizumab 80 mg Q4W or Q2W and 105 patients treated
with placebo.9
In
the 52-week placebo-controlled treatment period of COAST-X,
treatment-emergent high fasting serum glucose (defined as a change
from a fasting serum glucose value less than or equal to the ULN at
baseline, to a value more than the ULN at any time during the
treatment period) was reported in 6.2% of patients treated with
ixekizumab 80 mg Q2W and 10.6% of patients treated with ixekizumab 80
mg Q4W compared with 7.1% of patients in the placebo group. It should
be noted that these analyses were not conducted specifically in
patients with diabetes.6
Note: The
dosing schedule IXEQ2W is not consistent with the approved dosing
schedule for axial spondyloarthritis. Please refer to the Taltz
summary of product characteristics for approved dosing.1
References
1.
Taltz [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
2.
Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab
in moderate-to-severe plaque psoriasis. N Engl J Med.
2016;375(4):345-356. http://dx.doi.org/10.1056/NEJMoa1512711
3.
Wu JJ, Egeberg A, Solomon JA, et al. Ixekizumab treatment shows a
neutral impact on the glucose and lipid profile of patients with
moderate-to-severe psoriasis: results from UNCOVER-1, -2, and -3.
Poster presented at: 75th Annual Meeting of the American Academy of
Dermatology; March 3-7, 2017; Orlando, FL.
https://www.aad.org/eposters/Submissions/getFile.aspx?id=4662&type=sub
4.
Egeberg A, Wu JJ, Korman N, et al. Ixekizumab treatment shows a
neutral impact on cardiovascular parameters in patients with
moderate-to-severe plaque psoriasis: results from UNCOVER-1,
UNCOVER-2, and UNCOVER-3. J Am Acad Dermatol. 2018;79(1):104-109.
http://dx.doi.org/10.1016/j.jaad.2018.02.074
5.
Strober B, Leonardi C, Papp KA, et al. Short- and long-term safety
outcomes with ixekizumab from 7 clinical trials in psoriasis:
etanercept comparisons and integrated data. J Am Acad Dermatol.
2017;76(3):432-440.e17. http://dx.doi.org/10.1016/j.jaad.2016.09.026
6.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
7.
Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. Efficacy and safety
of ixekizumab in the treatment of radiographic axial
spondyloarthritis: sixteen-week results from a phase III randomized,
double-blind, placebo controlled trial in patients with prior
inadequate response to or intolerance of tumor necrosis factor
inhibitors. Arthritis Rheumatol. 2019;71(4):599-611.
http://dx.doi.org/10.1002/art.40753
8.
van der Heijde D, Cheng-Chung Wei J, Dougados M, et al. Ixekizumab,
an interleukin-17A antagonist in the treatment of ankylosing
spondylitis or radiographic axial spondyloarthritis in patients
previously untreated with biological disease-modifying anti-rheumatic
drugs (COAST-V): 16 week results of a phase 3 randomised,
double-blind, active-controlled and placebo-controlled trial. Lancet.
2018;392(10163):2441-2451.
http://dx.doi.org/10.1016/s0140-6736(18)31946-9
9.
Deodhar A, van der Heijde D, Gensler LS, et al. Ixekizumab for
patients with non-radiographic axial spondyloarthritis (COAST-X): a
randomised, placebo-controlled trial. Lancet.
2020;395(10217):53-64.
http://dx.doi.org/10.1016/S0140-6736(19)32971-X
Glossary
AS/r-axSpA
= ankylosing spondylitis/radiographic axial spondyloarthritis
axSpA
= axial spondyloarthritis
CV =
cardiovascular
Lilly
= Eli Lilly and Company
nr-axSpA
= nonradiographic axial spondyloarthritis
PsA
= psoriatic arthritis
Q2W
= every 2 weeks
Q4W
= every 4 weeks
TEAE
= treatment-emergent adverse event
ULN
= upper limit of normal