Taltz ® (ixekizumab) injection

80 mg/mL

This 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.

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.

US_cFAQ_IXE049_X1_COMPARISON_TREMFYA_PsO
US_cFAQ_IXE049_X1_COMPARISON_TREMFYA_PsO
en-US

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

IXORA-R: PASI 100, PASI 90, and sPGA (0) Efficacy Endpoints, ITT Population, NRI2

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.

IXORA-R: Response Rates of the Gated Primary and Major Secondary Efficacy Endpoints, ITT Population, NRI1,2

 

Guselkumab
(N=507)
n (%)

Ixekizumab
(N=520)
n (%)

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

IXORA-R: Safety Overview Through Week 242,4

 

Guselkumab
(N=506)
n (%)

Ixekizumab
(N=519)
n (%)

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.

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.

eThe potential anaphylaxis was related to the use of amoxicillin.

fNumbers 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.

gPositively adjudicated by external committee.

hPatient had a prior history of ulcerative colitis.

iOne case of ulcerative colitis was reported during the follow-up period for a patient who had received ixekizumab.

jPatients 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 12 may be accessed here and 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

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; 2021.

6Tremfya [package insert]. Horsham, PA: Janssen Biotech, Inc; 2020.

Date of Last Review: September 04, 2020


Contact Lilly

Call Us

If you need information about a Lilly product or want to report an Adverse Event or Product Complaint, you may call us.

Available Mon - Fri, 9am - 7pm EST

Or you can

Chat with us

Chat with us

Submit a Request

Visit Us @LillyMedical