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Taltz ® (ixekizumab) injection
80 mg/mL
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How does Taltz® (ixekizumab) compare with Tremfya® (guselkumab) for psoriasis?
Ixekizumab was superior to guselkumab in achievement of the primary endpoint of PASI 100 at week 12 in IXORA-R.
IXORA-R: Head-to-Head Trial of Ixekizumab and Guselkumab in Plaque Psoriasis
Efficacy Results
As shown in IXORA-R: PASI 100, PASI 90, and sPGA (0) Efficacy Endpoints, ITT Population, NRI and IXORA-R: Response Rates of the Gated Primary and Major Secondary Efficacy Endpoints, ITT Population, NRI, ixekizumab met the primary endpoint by demonstrating superiority at week 12 in the proportion of patients who achieved complete skin clearance compared with guselkumab as measured by a 100% improvement from baseline in Psoriasis Area and Severity Index (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 50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50)
- week 2 for 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75), and
- week 4 for static Physician Global Assessment score of 0 [sPGA (0)], 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90), and PASI 100.1
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.2,3
Figure 1 description: In the IXORA-R clinical trial, at the end of the week 24, similar percentages of patients receiving ixekizumab and guselkumab achieved, 100% improvement from baseline in Psoriasis Area and Severity Index, 90% improvement from baseline in Psoriasis Area and Severity Index, and static Physician Global Assessment score of 0.
Abbreviations: GUS = guselkumab; ITT = intent-to-treat; IXE = ixekizumab; NRI = nonresponder imputation; PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index; PASI 100 = 100% improvement from baseline in 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.
|
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 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; sPGA = static Physician Global Assessment.
aComparisons in the ITT population were made using Cochran-Mantel-Haenszel test adjusted by pooled site using nonresponder imputation for missing data.
bSecondary 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
IXORA-R: Safety Overview Through Week 24 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.2
|
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)e |
4 (0.8)f |
Allergic reactions |
13 (3) |
19 (4) |
Potential anaphylaxisg |
1 (0.2) |
0 |
Injection site reactionsh |
19 (4) |
67 (13) |
MACEi |
2 (0.4) |
4 (0.8) |
Cerebrocardiovascular eventsi |
4 (0.8) |
7 (1) |
Inflammatory bowel diseasei |
0 |
1 (0.2) |
Crohn's disease |
0 |
1 (0.2)j |
Ulcerative colitisk |
0 |
0 |
Hepatic eventsl |
8 (2) |
7 (1) |
Abbreviations: AE = adverse event; MACE = major adverse cardiac events; MedDRA = Medical Dictionary for Regulatory Activities; TEAEs = treatment-emergent adverse events.
aPatients with multiple occurrences of the same event are counted under the highest severity.
bCommon TEAEs are defined as TEAEs that occurred at a frequency of ≥3% overall.
cNumbers reported here only include TEAEs with the MedDRA low-level term "injection site reaction."
dThe opportunistic infections identified by investigators were mucocutaneous candidiasis and herpes zoster.
e n=2 basal cell carcinoma cases; n=1 endometrial cancer stage IV.
fn=2 basal cell carcinoma cases; n=1 rhabdomyosarcoma; n=1 squamous cell carcinoma case (1 patient had both squamous cell carcinoma on shoulder and keratoacanthoma type on abdomen).
gThe potential anaphylaxis was related to the use of amoxicillin.
hNumbers 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.
iPositively adjudicated by external committee.
jPatient had a prior history of ulcerative colitis.
kOne case of ulcerative colitis was reported during the follow-up period for a patient who had received ixekizumab.
lPatients with at least 1 hepatic-related TEAE.
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.1
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 every 2 weeks through week 12 then ixekizumab 80 mg every 4 weeks, or
- guselkumab 100 mg at week 0 and week 4, then guselkumab 100 mg every 8 weeks.1
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 12.1
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 12.1
Additional study design details, baseline characteristics, and outcomes are available in the published manuscripts.1,2
A detailed visual representation of the IXORA-R trial results through week 24 may be accessed here.
Ixekizumab and Guselkumab Mechanism of Action and Structure
Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody that selectively binds with the interleukin-17A (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.5
Guselkumab is a human immunoglobulin G subclass 1λ (IgG1λ) monoclonal that selectively binds to the p19 subunit of interleukin-23 (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.6
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Blauvelt A, Papp K, Gottlieb A, et al; the IXORA-R Study Group. 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
2Blauvelt A, Leonardi C, Elewski B, et al; the IXORA-R Study Group. 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. 2021;184(6):1047-1058. https://doi.org/10.1111/bjd.19509
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
4Blauvelt 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.
5Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.
6Tremfya [package insert]. Horsham, PA: Janssen Biotech, Inc; 2020.
Date of Last Review: July 26, 2023