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How does ixekizumab compare with 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
This medical response may not completely match the information in the current local labeling for IXEKIZUMAB. Please see local labeling for approved label information.
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
Randomization was stratified by concomitant cDMARD use at baseline and moderate-to-severe plaque PsO involvement at baseline (defined in this study as meeting all 3 criteria: PASI ≥12, sPGA ≥3, and BSA ≥10%).2
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. As shown in , significant differences in achieving simultaneous ACR50 and PASI 100 responses were observed as early as week 8 and continued through week 52.2,3
Major Secondary Endpoints: Achievement of ACR50 and PASI 100 at Week 24
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 ).2,3
Additional Secondary Outcomes
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).2,4
Patient-Reported Quality of Life Outcomes
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).5
Responses were similar between ixekizumab and adalimumab for the proportion of patients who achieved MCID for HAQ-DI and change from baseline in SF-36 PCS at week 52. Compared with the adalimumab group, patients in the ixekizumab group had significantly greater improvements in skin-related quality of life as measured by DLQI (0,1) at week 52 (p=.014), with significant differences observed as early as week 4.3
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.6
The ACR20 and ACR50 response rates were not statistically significantly different between the ixekizumab and adalimumab groups for any of the evaluated baseline characteristics.6
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).6
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).6
The percentages of patients who achieved MDA (6 entheseal points) was similar among the ixekizumab and adalimumab groups for the other evaluated subgroups.6
Efficacy by Baseline Severity of Psoriasis
A subgroup analysis of efficacy by presence or absence of moderate-to-severe psoriasis found that the efficacy of ixekizumab was not influenced by baseline psoriasis severity.3
Efficacy by Baseline Use of Methotrexate
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.4
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.7
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.3,7
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).8
Consistency of Response Over Time
shows the proportion of patients who achieved ACR50 and DAPSA ≤14 (LDA) at week 24 and maintained the response out to week 52 with some fluctuations of response between ACR50 and ACR20 or between LDA and moderate disease activity. This post hoc analysis demonstrated a numerically higher proportion of patients treated with ixekizumab compared with adalimumab showed consistency of response, as measured by ACR50 and DAPSA responses, over time.9
DAPSA ≤14 LDA
DAPSA ≤14 LDA
Patients who achieved response at week 24
Achieved response at week 24 and maintained out to week 52 with some fluctuationsa
Maintained response at every visit
Had some fluctuations of response
Abbreviations: ACR20 = 20% improvement from baseline in American College of Rheumatology response; ACR50 = 50% improvement from baseline in American College of Rheumatology response; DAPSA = Disease Activity in Psoriatic Arthritis; LDA = low disease activity; MDA = moderate disease activity; NRI = nonresponder imputation.
aPatients had fluctuations of response between ACR50 and ACR20 or between LDA and MDA.
Ixekizumab vs Adalimumab SPIRIT-H2H Safety Results
In SPIRIT-H2H, the safety profiles of ixekizumab and adalimumab were consistent with previously reported results and approved label information.2
The frequencies of AEs were similar in the adalimumab and ixekizumab treatment groups in subgroups of patients who received monotherapy or concomitant csDMARD therapy.7
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.
1Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2Mease PJ, Smolen JS, Behrens F, et al; The SPIRIT H2H Study Group. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis. 2020;79(1):123-131. https://doi.org/10.1136/annrheumdis-2019-215386
3Smolen JS, Mease P, Tahir H, et al. Multicentre, randomised, open-label-parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis. 2020;79(10):1310-1319. http://dx.doi.org/10.1136/annrheumdis-2020-217372
4Smolen J, Nash P, Tahir H, et al. A head-to-head comparison of ixekizumab and adalimumab in biologic-naïve 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.
5Mease PJ, Smolen JS, 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 naive to biologic disease-modifying anti-rheumatic drugs: 24-week results. Ann Rheum Dis. 2019;78(suppl 2):261-262. European League Against Rheumatism abstract LB0005. http://dx.doi.org/10.1136/annrheumdis-2019-eular.8709
6Merola 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.
7Smolen, JS, Sebba A, Ruderman E, et al. Efficacy and safety of ixekizumab versus adalimumab (SPIRIT-H2H) with and without concomitant conventional synthetic disease-modifying antirheumatic drugs (DMARD) in biologic DMARD-naïve patients with psoriatic arthritis: 52-week results. Ann Rheum Dis. 2020;79(suppl 1):143-144. Annual European Congress of Rheumatology abstract OP0228. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4615
8Smith 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.
9Coates LC, Sandoval D, Bolce R, et al. Ixekizumab treatment response: consistency over time and at each visit in psoriatic arthritis. Abstract presented at: European League Against Rheumatism Virtual Congress; June 2-5, 2021.
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
LDA = low disease activity
LDI-B = Leeds Dactylitis Index-Basic
LEI = Leeds Enthesitis Index
MCID = mean clinically important difference
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
PCS = Physical Component Summary
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
Fecha de la última revisión: 2021 M05 11