Ixekizumab
Label Information
Ixekizumab
is contraindicated in patients with clinically important active
infections (e.g. active tuberculosis).1
Ixekizumab
must not be given to patients with active tuberculosis (TB). Consider
anti-TB therapy prior to initiation of ixekizumab in patients with
latent TB.1
Reactivation
of LTBI has been reported with the use of other immunosuppressive
agents.2,3
Integrated
data from clinical trials of ixekizumab in psoriasis, PsA, and axSpA
showed no confirmed cases of TB reactivation.4,5
Treatment
with ixekizumab is associated with an increased rate of infections
such as upper respiratory tract infection, oral candidiasis,
conjunctivitis, and tinea infections.1
Ixekizumab
should be used with caution in patients with clinically important
chronic infection or a history of recurrent infection. Patients
should be instructed to seek medical advice if signs or symptoms
suggestive of an infection occur. If an infection develops, monitor
carefully and discontinue ixekizumab if the patient is not responding
to standard therapy or the infection becomes serious. Ixekizumab
should not be resumed until the infection resolves.1
Tuberculosis
Screening in Ixekizumab Clinical Trials
Patients
were screened for TB using chest x-rays, PPD skin tests, or QFT.6,7
Patients who
tested
negative were retested yearly, with the exception of axSpA trials,
in which no retesting for TB was required6,7
tested
positive for TB but had no evidence of TB infection were allowed to
participate in the trial if they received at least 4 weeks of
appropriate LTBI therapy, with the completion of the therapy during
the course of the study6,7
had
evidence or suspicion of active TB were excluded from ixekizumab
clinical trials,6,7
and
had
household contact with a person with active TB were excluded, unless
appropriate and documented prophylaxis for TB was given.7,8
Tuberculosis
Treatment-Emergent Adverse Events From 16 Psoriasis Clinical Trials
In
an integrated safety analysis of all ixekizumab adult and pediatric
psoriasis exposures (N=6645; PY=17,902.0) across 16 plaque psoriasis
trials as of March 19, 2020, potential TB infection (using broad
MedDRA-preferred terms) was reported in 59 (0.9%) patients (IR=0.3
per 100 PYs), of which
42
(0.6%) had a positive Mycobacterium tuberculosis complex test, and
17
(0.3%) had a positive tuberculin test.7
Opportunistic
TB infection (using narrow MedDRA-preferred terms) was reported in 2
(0.0%) patients (pulmonary TB, n=1; TB, n=1).7
Tuberculosis
Treatment-Emergent Adverse Events From 4 Psoriatic Arthritis Clinical
Trials
In
an integrated safety analysis of all ixekizumab PsA exposures
(N=1401; PY=2247.7) across 4 PsA trials as of March 19, 2020,
potential TB infection (using broad MedDRA-preferred terms) was
reported in 7 (0.5%) patients (IR=0.3 per 100 PYs), of which
5
(0.4%) had a positive tuberculin test, and
2
(0.1%) had a positive Mycobacterium tuberculosis complex test.7
Tuberculosis
Treatment-Emergent Adverse Events From 4 Axial Spondyloarthritis
Clinical Trials
In
an integrated analysis of 932 patients (1849.0 PY) who received
ixekizumab across 4 trials in patients with AS/r-axSpA and nr-axSpA
as of March 19, 2020, no cases of TB were reported.9
Post
Hoc Analysis of Integrated Safety Data in Psoriasis and Psoriatic
Arthritis Clinical Trials
A
post hoc analysis of integrated safety data from 16 clinical trials
in patients with psoriasis and PsA evaluated the incidence of
treatment-emergent LTBI in patients who received ixekizumab. The
analysis included data from 13 psoriasis clinical trials (N=5898;
16,313 PY) and 3 PsA clinical trials (N=1118; 1822 PY).5
Of
the 5898 patients from the psoriasis clinical trials included in the
analysis, 101 (1.7%) developed treatment-emergent LTBI. A total of 36
patients continued in the study, and 30 of those patients received
LTBI treatment.5
Of
the 1118 patients from the PsA clinical trials included in the
analysis, 32 (2.9%) developed treatment-emergent LTBI. A total of 12
patients continued in the study, and 7 of those patients received
LTBI treatment.5
No
cases of reactivation of TB were identified in this safety analysis.5
References
1.
Taltz [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
2.
Fallahi-Sichani M, Flynn JL, Linderman JJ, Kirschner DE.
Differential risk of tuberculosis reactivation among anti-TNF
therapies is due to drug binding kinetics and permeability.
J Immunol. 2012;188(7):3169-3178.
http://dx.doi.org/10.4049/jimmunol.1103298
3.
Xie X, Li F, Chen JW, Wang J. Risk of tuberculosis infection in
anti-TNF-α biological therapy: from bench to bedside. J
Microbiol Immunol Infect. 2014;47(4):268-274.
http://dx.doi.org/10.1016/j.jmii.2013.03.005
4.
Genovese MC, Mysler E, Tomita T, et al. Safety of ixekizumab in
adult patients with plaque psoriasis, psoriatic arthritis and axial
spondyloarthritis: data from 21 clinical trials. Rheumatology
(Oxford). Published online May 25, 2020.
https://doi.org/10.1093/rheumatology/keaa189
5.
Mrowietz U, Riedl E, Winkler S, et al. No reactivation of
tuberculosis in patients with latent tuberculosis infection receiving
ixekizumab: a report from 16 clinical studies of patients with
psoriasis or psoriatic arthritis. J Am Acad Dermatol.
2020;83(5):1436-1439. https://doi.org/10.1016/j.jaad.2020.06.012
6.
Riedl E, Winkler S, Xu W, et al. No reactivation of tuberculosis in
psoriasis patients with latent tuberculosis infection while on
ixekizumab treatment: a report from 11 clinical studies. Abstract
presented at: 27th Congress of the European Academy of Dermatology
and Venereology; September 12-16, 2018; Paris, France.
7.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
8.
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
9.
Schwartzman S, Sandoval D, Kronbergs A, et al. Long-term safety
profile of ixekizumab treatment on patients with axial
spondyloarthritis. Abstract presented at: American College of
Rheumatology/ARP 2020 Annual Scientific Meeting (Virtual); November
5-9, 2020.
Glossary
AS/r-axSpA
= ankylosing spondylitis/radiographic axial spondyloarthritis
axSpA
= axial spondyloarthritis
IR =
incidence rate
LTBI
= latent tuberculosis infection
MedDRA
= Medical Dictionary for Regulatory Activities
nr-axSpA
= nonradiographic axial spondyloarthritis
PPD
= purified protein derivative skin test
PsA
= psoriatic arthritis
PY =
patient-years
QFT
= QuantiFERON®-TB Gold
TB =
Tuberculosis