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Taltz ® (ixekizumab) injection
80 mg/mLThis information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Ixekizumab and Guselkumab Mechanism of Action and Structure
Ixekizumab is a humanized IgG4 mAb that selectively binds with the IL-17A cytokine and inhibits its interaction with the IL-17 receptor. Interleukin-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.1
Guselkumab is a human IgG1λ mAb that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Interleukin-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Guselkumab inhibits the release of proinflammatory cytokines and chemokines.2
IXORA-R: Head-to-Head Trial of Ixekizumab and Guselkumab in Plaque Psoriasis
Study Design
IXORA-R (study I1F-MC-RHCR) was a 24-week, multicenter, double-blind, randomized, parallel-group phase 4 study designed to evaluate the efficacy and safety of ixekizumab compared with guselkumab in adult patients with moderate-to-severe plaque psoriasis. The trial was designed to examine speed of response with multiple major secondary endpoints at early time points.3
Patients were randomized 1:1 to ixekizumab (N=520) or guselkumab (N=507). Dosing regimen was the approved label dosing, which is either
ixekizumab 160 mg starting dose at week 0 followed by ixekizumab 80 mg Q2W through week 12 then ixekizumab 80 mg Q4W, or
guselkumab 100 mg at week 0 and week 4, then guselkumab 100 mg Q8W.3
The primary endpoint of IXORA-R assessed whether ixekizumab was superior to guselkumab as measured by the proportion of patients achieving PASI 100 at week 12.3
The major secondary endpoints of IXORA-R were the proportion of patients achieving
PASI 50 at week 1
PASI 75 at week 2
PASI 90 at weeks 4 and 8
PASI 100 at weeks 4, 8, and 24, and
sPGA (0) at week 12.3
Efficacy Results
As shown in Figure 1 and Table 1, ixekizumab met the primary endpoint by demonstrating superiority at week 12 in the proportion of patients achieving complete skin clearance compared to guselkumab as measured by PASI 100 and all major secondary endpoints up to week 12. More patients on ixekizumab showed improvement over guselkumab as early as
week 1 for PASI 50
week 2 for PASI 75, and
week 4 for sPGA (0), PASI 90, and PASI 100.3
Secondary efficacy endpoint, PASI 100 at week 24, was type-I error controlled but did not achieve superiority. Noninferiority analysis of PASI 100 at week 24 was prespecified and achieved but was not type-I error controlled.4,5
Figure 1. IXORA-R: PASI 100, PASI 90, and sPGA (0) Efficacy Endpoints, ITT Population, NRI4
Abbreviations: GUS = guselkumab; ITT = intent-to-treat; IXE = ixekizumab; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; sPGA = static Physician Global Assessment.
‡ p<.05 vs GUS.
† p<.01 vs GUS.
* p<.001 vs GUS.
Black box indicates the primary endpoint for the study.
PASI 100 at weeks 4, 8, 12, and 24; PASI 90 at weeks 4 and 8; and sPGA (0) at week 12 were type-I error controlled. All other analyses were not type-I error controlled.
Table 1. IXORA-R: Response Rates of the Gated Primary and Major Secondary Efficacy Endpoints, ITT Population, NRI3,4
|
Guselkumab |
Ixekizumab |
P Valuea |
Primary efficacy endpoint |
|||
PASI 100 at week 12 |
126 (25) |
215 (41) |
<.001 |
Major secondary endpoints |
|||
PASI 50 at week 1 |
47 (9) |
143 (28) |
<.001 |
PASI 75 at week 2 |
26 (5) |
119 (23) |
<.001 |
PASI 90 at week 4 |
40 (8) |
109 (21) |
<.001 |
PASI 90 at week 8 |
182 (36) |
304 (58) |
<.001 |
PASI 100 at week 4 |
7 (1) |
35 (7) |
<.001 |
PASI 100 at week 8 |
69 (14) |
154 (30) |
<.001 |
sPGA (0) at week 12 |
128 (25) |
218 (42) |
<.001 |
PASI 100 at week 24b |
265 (52) |
260 (50) |
.414 |
Abbreviations: ITT = intent-to-treat; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; sPGA = static Physician Global Assessment.
a Comparisons in the ITT population were made using Cochran-Mantel-Haenszel test adjusted by pooled site using nonresponder imputation for missing data.
b Secondary efficacy endpoint, PASI 100 at week 24, was type-I error controlled but did not achieve superiority. Noninferiority analysis of PASI 100 at week 24 was prespecified and achieved but was not type-I error controlled.
Safety Data
Table 2 presents an overview of the safety data for all patients who received ≥1 dose of either drug. The authors concluded that the safety profiles of ixekizumab and guselkumab were consistent with previous studies.4
Table 2. IXORA-R: Safety Overview Through Week 244,6
|
Guselkumab |
Ixekizumab |
TEAE overall |
286 (57) |
323 (62) |
Severea |
21 (4) |
18 (3) |
Death |
0 |
0 |
Serious adverse event |
16 (3) |
18 (3) |
Discontinuation due to AE |
8 (2) |
15 (3) |
Common TEAEsb |
||
Upper respiratory tract infection |
41 (8) |
40 (8) |
Nasopharyngitis |
27 (5) |
34 (7) |
Injection site reactionc |
6 (1) |
49 (9) |
Headache |
15 (3) |
22 (4) |
Diarrhea |
17 (3) |
16 (3) |
AEs of special interest |
||
Neutropenias |
2 (0.4) |
2 (0.4) |
Infections |
143 (28) |
162 (31) |
Serious infections |
2 (0.4) |
2 (0.4) |
Opportunistic infectionsd |
1 (0.2) |
5 (1) |
Mucocutaneous candidiasis |
0 |
3 (0.6) |
Herpes zoster |
1 (0.2) |
2 (0.4) |
Reactivated tuberculosis |
0 |
0 |
Depression |
7 (1) |
5 (1) |
Malignancies |
3 (0.6) |
4 (0.8) |
Allergic reactions |
13 (3) |
19 (4) |
Potential anaphylaxise |
1 (0.2) |
0 |
Injection site reactionsf |
19 (4) |
67 (13) |
MACEg |
2 (0.4) |
4 (0.8) |
Cerebrocardiovascular eventsg |
4 (0.8) |
7 (1) |
Inflammatory bowel diseaseg |
0 |
1 (0.2) |
Crohn's disease |
0 |
1 (0.2)h |
Ulcerative colitisi |
0 |
0 |
Hepatic eventsj |
8 (2) |
7 (1) |
Abbreviations: AE = adverse event; MACE = major adverse cardiac events; MedDRA = Medical Dictionary for Regulatory Activities; TEAEs = treatment-emergent adverse events.
a Patients with multiple occurrences of the same event are counted under the highest severity.
b Common TEAEs are defined as TEAEs that occurred at a frequency of ≥3% overall.
c Numbers reported here only include TEAEs with the MedDRA low-level term "injection site reaction."
d The opportunistic infections identified by investigators were mucocutaneous candidiasis and herpes zoster.
e The potential anaphylaxis was related to the use of amoxicillin.
f Numbers reported here are for the high-level MedDRA term “injection site reactions” which includes multiple lower-level MedDRA terms, including but not limited to, injection site reaction, injection site pain, injection site erythema, injection site swelling, injection site pruritus, injection site discomfort, injection site edema, and injection site warmth.
g Positively adjudicated by external committee.
h Patient had a prior history of ulcerative colitis.
i One case of ulcerative colitis was reported during the follow-up period for a patient who had received ixekizumab.
j Patients with at least 1 hepatic-related TEAE.
Ixekizumab and Guselkumab in Psoriatic Arthritis: Lack of Head-to-Head Data
Lilly has not conducted any studies to compare the safety and efficacy of ixekizumab to that of guselkumab in patients with psoriatic arthritis.
As clinical trials are conducted under widely varying and controlled conditions, efficacy outcomes and adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Enclosed Prescribing Information
TALTZ® (ixekizumab) injection, for subcutaneous administration, Lilly
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.
2. Tremfya [package insert]. Horsham, PA: Janssen Biotech, Inc; 2020.
3. Blauvelt A, Papp K, Gottlieb A, et al. A head-to-head comparison of ixekizumab versus guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety, and speed of response from a randomized, double-blinded trial. Br J Dermatol. 2020;182(6):1348-1358. http://dx.doi.org/10.1111/bjd.18851
4. Blauvelt A, Leonardi C, Elewski B, et al. A head-to-head comparison of ixekizumab versus guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomised, double-blinded trial. Br J Dermatol. Published online September 02, 2020. http://dx.doi.org/10.1111/bjd.19509
5. Data on file, Eli Lilly and Company and/or one of its subsidiaries.
6. Blauvelt A, Pinter A, Tada Y, et al. Ixekizumab vs guselkumab: 24-week clinical responses and 4-week gene expression data. Poster presented at: Maui Derm Virtual Congress; June 24-27, 2020.
Glossary
IgG1 = immunoglobulin G subclass 1
IgG4 = immunoglobulin G subclass 4
IL = interleukin
Lilly = Eli Lilly and Company
mAb(s) = monoclonal antibody
PASI 50 = 50% improvement from baseline in Psoriasis Area and Severity Index
PASI 75 = 75% improvement from baseline in Psoriasis Area and Severity Index
PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index
PASI 100 = 100% improvement from baseline in Psoriasis Area and Severity Index
Q2W = every 2 weeks
Q4W = every 4 weeks
Q8W = every 8 weeks
sPGA = static Physician Global Assessment
Date of Last Review: September 04, 2020
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