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 HUMIRA® (adalimumab) for Psoriatic Arthritis and Psoriasis?

Ixekizumab was superior to adalimumab in achievement of the simultaneous primary endpoint of ACR50 and PASI 100. No head to head studies have been conducted for psoriasis.

Ixekizumab vs Adalimumab in Psoriatic Arthritis

Ixekizumab vs Adalimumab SPIRIT-H2H Study Design

Design and Dosing Arms

SPIRIT-H2H (N=566) is a 52-week randomized, open-label, parallel-group, phase 3b/4 clinical trial with blinded assessor to evaluate the efficacy and safety of ixekizumab with that of adalimumab in patients with active PsA (≥3 TJC and ≥3 SJC) and plaque PsO (BSA ≥3%) at baseline who are bDMARD-naive. The blinded assessors were not allowed to know the patient's treatment allocation or to be otherwise involved in the study procedures. To be qualified as a blinded assessor, a minimum of 1-year of experience using the instrument tools was required.1

For patients randomized to ixekizumab who met the study’s definition of moderate-to-severe PsO, ixekizumab was administered 80 mg Q2W from week 2 to 12 after a 160 mg starting dose at week 0, and Q4W thereafter. For all other patients randomized to ixekizumab, dosing was ixekizumab 80 mg Q4W after a 160 mg starting dose at week 0.2

For patients randomized to adalimumab who met the study’s definition of moderate-to-severe PsO, adalimumab was administered 80 mg at week 0, followed by 40 mg Q2W starting at week 1. For all other patients randomized to adalimumab, dosing was adalimumab 40 mg Q2W.2

Patient Population

Enrolled patients (N=566) had active PsA (defined as the presence of at least 3 tender and at least 3 swollen joints) and plaque psoriasis with BSA ≥3%, had an inadequate response to at least one cDMARD, and were bDMARD naive.2

After week 24 database lock and initial analysis run, a medical inconsistency in baseline PASI data was identified. Although 9 patients were assessed as PASI=0 at baseline, those patients fulfilled the criteria for having psoriasis as assessed by a BSA ≥3%. Therefore, these patients were judged as PASI 100 responders if they achieved an absolute PASI=0 and BSA=0 at post baseline visits. Multiple analyses to assess the robustness of this approach were conducted.2

Ixekizumab vs Adalimumab SPIRIT-H2H Efficacy Results

Primary Outcome: Simultaneous Achievement of ACR50 and PASI 100 at Week 24

Ixekizumab showed superior efficacy to adalimumab based on the primary outcome of the SPIRIT-H2H trial, simultaneous achievement of ACR50 and PASI 100 responses at week 24. The primary outcome at week 24 was controlled for type-1 error. As shown in Figure 1, significant differences in achieving simultaneous ACR50 and PASI 100 responses were observed as early as week 8 and continued through week 52.2

Figure 1. Percentage of Patients who Achieved Simultaneous ACR50 and PASI 100 in SPIRIT-H2H Through 52 Weeks by Treatment Week, NRI3

Abbreviations: ACR50 = 50% improvement from baseline in American College of Rheumatology Index; ADA = adalimumab; IXE = ixekizumab; NRI = nonresponder imputation; PASI 100 = 100% improvement from baseline in Psoriasis Area and Severity Index; W24 = week 24; W52 = week 52.

*p<.01 vs ADA.
† p<.05 vs ADA.
‡ p<.001 vs ADA.

Major Secondary Endpoints: Achievement of ACR50 and PASI 100 at Week 24

The 2 major secondary endpoints of noninferiority to adalimumab in ACR50 response and superiority to adalimumab in PASI 100 response at week 24 were controlled for type-1 error.2

As measured by ACR50, ixekizumab was noninferior to adalimumab (noninferiority margin, -12.0%) with no statistically significant differences in ACR50 response between the treatment arms through week 52 (see Figure 2).2

Figure 2. Percentage of Patients who Achieved ACR50 in SPIRIT-H2H Through 52 Weeks by Treatment Week, NRI 3

Abbreviations: ACR50 = 50% improvement from baseline in American College of Rheumatology Index; ADA = adalimumab; IXE = ixekizumab; NRI = nonresponder imputation; W24 = week 24; W52 = week 52.

The PASI 100 response was significantly greater in the ixekizumab treatment than in the adalimumab arm with statistically significant differences observed at the first PASI assessment at week 4 and every assessment through week 52 (see Figure 3).2

Figure 3. Percentage of Patients who Achieved PASI 100 Response in SPIRIT-H2H Through 52 Weeks by Treatment Week, NRI3

Abbreviations: ADA = adalimumab; IXE = ixekizumab; NRI = nonresponder imputation; PASI 100 = 100% improvement from baseline in Psoriasis Area and Severity Index; W24 = week 24; W52 = week 52.

*p≤.001 vs ADA.

Additional Secondary Outcomes

The additional secondary outcomes included in this response were not controlled for type-1 error.2

Greater improvements with ixekizumab than with adalimumab at week 24 were attained in

  • enthesitis resolution (via SPARCC and LEI)

  • composite outcomes (MDA, VLDA, DAPSA remission [score ≤4], and PASDAS near remission [score ≤1.9]), and

  • psoriasis skin assessments (PASI 75 and PASI 90).2,3

Responses were comparable between the treatment arms for ACR20, ACR70, and dactylitis resolution (via LDI-B) at week 24.2,3

Patient-Reported Quality of Life Outcomes at Week 24

Responses were similar between ixekizumab and adalimumab treatment groups for HAQ-DI and SF-36 component summaries. Change from baseline in DLQI was significantly better with ixekizumab treatment compared to adalimumab at week 24 (p<.001).4

Efficacy in Patient Subgroups at Week 24

A post hoc analysis compared ACR20, ACR50, ACR70, and MDA (6 entheseal points) results at week 24 between the ixekizumab and adalimumab groups by baseline

  • presence (LEI >0 or SPARCC >0) or absence (LEI =0 or SPARCC =0) of enthesitis

  • presence (LDI-B >0) or absence (LDI-B =0) of dactylitis

  • presence (NAPSI >0) or absence (NAPSI =0) of fingernail psoriasis

  • BSA with 10% cutoff, and

  • CRP with 6 mg/L cutoff.5

The ACR20 and ACR50 response rates were not statistically significantly different between the ixekizumab and adalimumab groups for any of the evaluated baseline characteristics.5

The ACR70 response rates were comparable between treatment groups for each of the evaluated baseline characteristics with the exception of baseline fingernail psoriasis. Compared with adalimumab, significantly more patients with fingernail psoriasis at baseline who received ixekizumab achieved ACR70 at week 24 (p<.05).5

The percentages of patients who achieved MDA (6 entheseal points) was significantly greater in the ixekizumab group than in the adalimumab group in subgroups of patients

  • with enthesitis (p<.01)

  • without dactylitis (p<.05)

  • with fingernail psoriasis (p<.001)

  • with CRP ≤6 mg/L (p<.05), and

  • with BSA ≥10% (p<.01).5

The percentages of patients who achieved MDA (6 entheseal points) was similar among the ixekizumab and adalimumab groups for the other evaluated subgroups.5

Efficacy By Baseline Use of Methotrexate at Weeks 24 and 52

The percentage of patients who achieved the primary endpoint of simultaneous ACR50 and PASI 100 responses at week 24 was consistent in the ixekizumab group regardless of concomitant methotrexate use.3

Efficacy by Baseline use of Concomitant Conventional Synthetic Disease-Modifying Antirheumatic Drugs Through 52 Weeks

The efficacy of ixekizumab compared with that of adalimumab through 52 weeks was stratified by baseline concomitant use of csDMARDs. A separate analysis was conducted by concomitant use of methotrexate.6

The efficacy of ixekizumab was sustained over 52 weeks regardless of whether it was taken as monotherapy or in combination with csDMARDS. Adalimumab was associated with numerically lower response rates when used as monotherapy rather than in combination with csDMARDs. Results from the separate analysis of concomitant use of methotrexate were similar to those of the broader csDMARD group.6

Efficacy in Nail Psoriasis at Week 24

A post hoc analysis of SPIRIT-H2H compared the efficacy of ixekizumab with that of adalimumab on nail PsO at 24 weeks in those patients with moderate-to-severe plaque PsO (defined in this study as PASI score ≥12, sPGA ≥3, and BSA involvement ≥10%) and NAPSI score ≥1. Significantly more patients who received ixekizumab achieved complete resolution of nail involvement (NAPSI=0) than did patients who received adalimumab (p<.01).7

Ixekizumab vs Adalimumab SPIRIT-H2H Safety Results

The safety profiles of ixekizumab and adalimumab were consistent with previously reported results and approved label information.3

The frequencies of AEs were similar in the adalimumab and ixekizumab treatment groups in subgroups of patients who received monotherapy or concomitant csDMARD therapy.6

Ixekizumab vs Adalimumab for Treatment of Psoriasis

No trials have been conducted that compare the efficacy and safety of ixekizumab to that of adalimumab in the treatment of psoriasis.

Enclosed Prescribing Information

TALTZ® (ixekizumab) injection, for subcutaneous administration, Lilly

References

The published references below are available upon request by contacting 1-800-545-5979 (1-800-LillyRx).

1. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2. Mease PJ, Smolen JS, Behrens F, et al. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naive patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis. 2020;79(1):123-131. http://dx.doi.org/10.1136/annrheumdis-2019-215386

3. Smolen J, Nash P, Tahir H, et al. A head-to-head comparison of ixekizumab and adalimumab in biologic-naive patients with active psoriatic arthritis: efficacy and safety outcomes from a randomized, open-label, blinded assessor study through 52 weeks. Poster presented at: American College of Rheumatology Annual Meeting; November 8-13, 2019; Atlanta, Georgia.

4. Mease P, Smolen J, Behrens F, et al. Multicentre, randomised, open-label, assessor-blinded, parallel-group head-to-head comparison of the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biologic disease-modifying anti-rheumatic drugs: 24-week results. Ann Rheum Dis. 2019;78(suppl 2):261-262. http://dx.doi.org/10.1136/annrheumdis-2019-eular.8709

5. Merola JF, Sprabery AT, Gellett AM, et al. Improvement in the signs and symptoms of psoriatic arthritis with ixekizumab compared to adalimumab in patient subgroups defined by baseline disease characteristics. Poster presented at: Annual Meeting of the American College of Rheumatology; November 8-13, 2019; Atlanta, Georgia.

6. Smolen, JS, Sebba A, Ruderman E, et al. Efficacy and safety of ixekizumab vs. adalimumab (SPIRIT-H2H) with and without concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in biological DMARD-naive patients with psoriatic arthritis: 52-week results. Ann of Rheum Dis. 2020;79(supp1);143-144. https://ard.bmj.com/content/annrheumdis/suppl/2020/06/01/79.Suppl_1.DC1/EULARAB-2020_completePDF.pdf

7. Smith SD, Kristensen LE, Schuster C, et al. Comparison of ixekizumab and adalimumab in the treatment of nail psoriasis in psoriatic arthritis patients with moderate-to-severe psoriasis: 24-week results from a multicentre, randomised, open-label, rater-blinded study (SPIRIT-H2H). Poster presented at: American Academy of Dermatology Virtual Meeting Experience; June 12-14, 2020.

Glossary

ACR20 = 20% improvement from baseline in American College of Rheumatology Index

ACR50 = 50% improvement from baseline in American College of Rheumatology Index

ACR70 = 70% improvement from baseline in American College of Rheumatology Index

AE = adverse event

bDMARD = biologic disease-modifying antirheumatic drug

BSA = body surface area

cDMARD = conventional disease-modifying antirheumatic drug

CRP = C-reactive protein

csDMARD = conventional synthetic disease-modifying antirheumatic drug

DAPSA = Disease Activity in Psoriatic Arthritis

DLQI = Dermatology Life Quality Index

HAQ-DI = Health Assessment Questionnaire-Disability Index

LDI-B = Leeds Dactylitis Index-Basic

LEI = Leeds Enthesitis Index

MDA = minimal disease activity

NAPSI = Nail Psoriasis Severity Index

PASDAS = PsA Disease Activity Score

PASI = 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

PsA = psoriatic arthritis

PsO = psoriasis

Q2W = every 2 weeks

Q4W = every 4 weeks

SF-36 = Medical Outcomes Study 36-Item Short Form Health Survey

SPARCC = Spondyloarthritis Research Consortium of Canada

sPGA = static Physician Global Assessment

SJC = swollen joint count

TJC = tender joint count

VLDA = Very Low Disease Activity 

Date of Last Review: April 07, 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, 8am - 7pm ET

Or you can

Ask us a question Chat with us

Submit a Request

Visit Us @LillyMedical