Taltz® (ixekizumab): Jämförelse med ustekinumab vid plackpsoriasis

Ixekizumab and Ustekinumab Head-to-Head Study in Plaque Psoriasis

Trial Overview

IXORA-S was a phase 3b, multicenter, randomized, double-blind, parallel-group study with 2 treatment arms. Patients were randomized to either

• ixekizumab 80 mg Q2W (following a 160 mg starting dose at week 0) through week 12 then ixekizumab 80 mg Q4W through week 52, or

• ustekinumab 45 mg for patients ≤100 kg and 90 mg for patients >100 kg at week 0, 4, 16, 28, and 40.

Patients received placebo injections as needed to maintain the study blind.¹

The primary objective of IXORA-S was to demonstrate ixekizumab noninferiority and superiority to ustekinumab, as measured by the proportion of patients achieving PASI 90 at week 12.¹

Efficacy

As shown in Figure 1, a significantly greater percentage of patients treated with ixekizumab achieved PASI 90, compared to those treated with ustekinumab, as early as week 4 and at all subsequent time points, including the primary endpoint of week 12.^1,2

Figure 2 includes results for PASI 75 and PASI 100 through week 52 in the ixekizumab and ustekinumab treatment groups, respectively.²

Figure 1. PASI 90 Response Rates Through Week 52, ITT Population, NRI²

Abbreviations: ITT = intent to treat; IXE = ixekizumab 160 mg starting dose followed by 80 mg every 2 weeks for the first 12 weeks and every 4 weeks through week 52; NRI = nonresponder imputation; PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index; UST = 45 mg ustekinumab given as subcutaneous injection for participants ≤100 kg and 90 mg subcutaneous injection for participants >100 kg at week 0, 4, 16, 28, and 40.

† p<.01 vs UST; ‡ p<.001 vs UST based on Fisher’s exact test.

Figure 2. PASI 75 and 100 Response Rates Through Week 52, ITT Population, NRI²

Abbreviations: ITT = intent to treat; IXE = ixekizumab 160 mg starting dose followed by 80 mg every 2 weeks for the first 12 weeks and every 4 weeks through week 52; NRI = nonresponder imputation; PASI = Psoriasis Area and Severity Index; UST = 45 mg ustekinumab given as subcutaneous injection for participants ≤100 kg and 90 mg subcutaneous injection for participants >100 kg at week 0, 4, 16, 28, and 40.

* p<.05 vs UST; † p<.01 vs UST; ‡ p<.001 vs UST based on Fisher’s exact test.

Efficacy in Nail Involvement

Patients in IXORA-S with baseline fingernail involvement (NAPSI>0) were assessed for improvements in NAPSI scores across 52 weeks of treatment. Each fingernail was scored for bed and matrix psoriasis; then scores were added to obtain total NAPSI fingernail scores ranging from 0 (no nail psoriasis) to 80 (severe nail psoriasis).³

Progressive improvement in NAPSI scores was seen in both groups, with complete resolution of nail psoriasis occurring in a significantly greater percentage of patients treated with ixekizumab compared to ustekinumab at week 16 (p=.02) and through week 52 (p<.001) as seen in Table 1.³

Table 1. Efficacy in Nail Lesions at Weeks 16 and 52 in Patients with Baseline Fingernail Psoriasis^3,4

	Ustekinumab	Ixekizumab
Patients with NAPSI > 0, n (%)	105 (63.3)	84 (61.8)
Baseline NAPSI total score, mean (SD)	24.8 (20.0)	28.3 (19.9)
Week 16 NAPSI = 0 by NRI, n (%)	17 (16.2)	26 (31.0)a
Week 52 NAPSI = 0 by NRI, n (%)	30 (28.6)	52 (61.9)b
NAPSI change from baseline at week 52 by mBOCF, LSM (95% CI)	-15.6 (-17.8, -13.4)	-22.4 (-24.8, -20.0)b

Abbreviations: LSM = least squares mean; mBOCF = modified baseline observation carried forward; NAPSI = nail psoriasis severity indicator; NRI = non-responder imputation; UST = ustekinumab.

^a p=.02 vs UST.

^b p<.001 vs UST.

Safety

Table 2 presents TEAEs reported through 52 weeks of IXORA-S.²

Through 52 weeks of treatment, no deaths were reported in either treatment group.²

Table 2. Treatment-Emergent Adverse Events Reported in IXORA-S After 52 Weeks of Treatment²

	Ustekinumab (N=166) n (%)	Ixekizumab (N=135)a n (%)	P Value
TEAEs	139 (83.7)	117 (86.7)	0.519
SAEs	14 (8.4)	10 (7.4)	0.832
AEs leading to discontinuation	2 (1.2)b	3 (2.2)c	0.660

Abbreviations: AE = adverse event; IXE = ixekizumab; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

^a One patient was randomized to the IXE group in error but not treated, as the patient was found to meet one of the exclusion criteria.

^b Pulmonary mass (n=1), transaminase increased (n=1).

^c Depression (n=1), exposure during pregnancy (n=1), injection-site hypersensitivity (n=1).

Additional Information

Ixekizumab is an IgG4 monoclonal antibody that binds with high affinity (< 3 pM) and specificity to interleukin 17A (both IL‑17A and IL‑17A/F). Elevated concentrations of IL‑17A have been implicated in the pathogenesis of psoriasis by promoting keratinocyte proliferation and activation. Neutralisation of IL‑17A by ixekizumab inhibits these actions. Ixekizumab does not bind to ligands IL‑17B, IL‑17C, IL‑17D, IL‑17E or IL‑17F.⁵

Ustekinumab is a human IgG1_Ⱪ mAb that binds with specificity to the p40 protein, a subunit of both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as NK cell activation.⁶

References

1. Reich K, Pinter A, Lacour JP, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017;177(4):1014-1023. http://dx.doi.org/10.1111/bjd.15666

2. Paul C, Griffiths CE, van de Kerkhof PC, et al. Ixekizumab provides superior efficacy compared to ustekinumab over 52-weeks of treatment: results from IXORA-S, a phase 3 study. J Am Acad Dermatol. 2019;80(1):70-79.e73. https://doi.org/10.1016/j.jaad.2018.06.039

3. Wasel N, Thaçi D, French LE, et al. Ixekizumab and ustekinumab efficacy in nail psoriasis in patients with moderate-to-severe psoriasis: 52-week results from a phase 3, head-to-head study (IXORA-S). Dermatol Ther (Heidelb). Published online May 15, 2020. https://doi.org/10.1007/s13555-020-00383-x

4. Wasel N, Dutronc Y, Schinzel B, Lacour JP. Comparison of ixekizumab and ustekinumab efficacy in the treatment of nail lesions of patients with moderate-to-severe plaque psoriasis: 52-week data from the IXORA-S trial. Abstract presented at: 27th Congress of the European Academy of Dermatology and Venereology (EADV); September 12-16, 2018; Paris, France.

5. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

6. Ustekinumab. Micromedex Health Solutions. Accessed November 6, 2017. http://www.micromedexsolutions.com/

Glossary

IgG1 = immunoglobulin G subclass 1

IgG4 = immunoglobulin G subclass 4

IL = interleukin

Lilly = Eli Lilly and Company

mAb(s) = monoclonal antibody

NAPSI = Nail Psoriasis Severity Index

NK = natural killer

PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index

PsA = psoriatic arthritis

Q2W = every 2 weeks

Q4W = every 4 weeks

TEAE = treatment-emergent adverse event