Session Information
Date: Monday, November 9, 2015
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease associated with psoriasis, peripheral arthritis, enthesitis, dactylitis, and spondylitis. PsA has a significant negative impact on patients’ quality of life, physical function, and work productivity. Ixekizumab is an IgG4 monoclonal antibody that binds with high affinity and specificity to the proinflammatory cytokine IL-17A, currently under investigation for the treatment of PsA.
Methods: In this phase 3 trial, 417 biologic disease-modifying antirheumatic drug (bDMARD)-naive patients with active PsA were randomized to receive up to 24 weeks of placebo (N=106); adalimumab 40 mg once every 2 weeks (Q2W; N=101) (active control); or ixekizumab 80 mg every 4 weeks (Q4W; N=107) or Q2W (N=103) following a 160 mg starting dose at Week 0. Patient Reported Outcomes (PROs) included, but were not limited to, Health Assessment Questionnaire – Disability Index (HAQ-DI), Short Form-36 Health Survey Physical Component Score (SF-36 PCS), European Quality of Life 5 Dimensions Visual Analog Scale (EQ-5D VAS), and Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP), and were analyzed using the intent-to-treat population. Continuous PRO data were evaluated using a mixed-effects model for repeated measures. The model included data up to Week 24 for all patients except inadequate responders (IRs) for whom data after Week 16 were excluded. Categorical PRO data were compared using a logistic regression model; missing values were imputed with the non-responder imputation method, treating IRs as non-responders.
Results: Across treatment groups, baseline demographics and clinical characteristics were generally similar; population mean baseline scores for HAQ-DI, SF-36 PCS, and EQ-5D VAS were 1.17, 33.63, and 55.4, respectively, indicating reduced physical function and quality of life. Mean baseline scores for the individual components of the WPAI-SHP assessment were 8.6 for Absenteeism, 36.6 for Presenteeism, 38.9 for Work Productivity, and 47.0 for Activity Impairment. At Week 12, patients treated with either ixekizumab 80 mg Q4W or Q2W reported significantly greater improvements compared to placebo in HAQ-DI, SF-36, EQ-5D VAS, and WPAI-SHP (all components, except Absenteeism); improvements were maintained through Week 24 for all treatment groups (Table). Additionally at Weeks 12 and 24, the percentage of patients with a baseline HAQ-DI score ≥0.35 achieving minimally clinically important difference (MCID) for HAQ-DI (improvement from baseline in HAQ-DI ≥0.35) was significantly greater in both ixekizumab treatment arms compared to placebo (Table).
Conclusion: In bDMARD-naive patients with active PsA, ixekizumab significantly improved quality of life, physical function and work productivity.
Table. PROs at Weeks 12 and 24 by treatment group.
|
Change from Baseline (SE) |
Placeboa (N=106) |
Adalimumab 40 mg Q2W (N=101) |
Ixekizumab 80 mg Q4W (N=107) |
Ixekizumab 80 mg Q2W (N=103) |
||||
|
Week 12 |
Week 24 |
Week 12 |
Week 24 |
Week 12 |
Week 24 |
Week 12 |
Week 24 |
|
|
HAQ-DIb |
-0.13 (0.05) |
-0.18 (0.05) |
-0.35 (0.05)** |
-0.37 (0.05)* |
-0.37 (0.05)** |
-0.44 (0.05)** |
-0.47 (0.05)** |
-0.50 (0.05)** |
|
SF-36 PCSc |
2.27 (0.79) |
2.94 (0.96) |
5.71 (0.82)** |
6.78 (0.90)* |
5.76 (0.80)** |
7.45 (0.89)** |
7.64 (0.81)** |
8.24 (0.90)** |
|
EQ-5D VASc |
3.2 (2.0) |
3.8 (2.4) |
9.2 (2.1)* |
10.3 (2.2)* |
12.3 (2.0)** |
11.9 (2.2)* |
14.7 (2.1)** |
13.1 (2.2)* |
|
WPAI-SHP: Absenteeismb |
-1.3 (1.6) |
-0.2 (3.2) |
-3.2 (1.6) |
-0.5 (2.5) |
-4.6 (1.5) |
-5.5 (2.6) |
-3.4 (1.6) |
0.9 (2.8) |
|
WPAI-SHP: Presenteeismb |
-4.8 (2.9) |
-6.8 (3.2) |
-9.9 (2.9) |
-13.2 (2.7) |
-14.8 (2.8)* |
-19.4 (2.6)** |
-18.2 (3.0)** |
-22.1 (2.8)** |
|
WPAI-SHP: Work Productivityb |
-5.4 (3.1) |
-8.3 (3.5) |
-11.7 (3.1) |
-13.4 (3.0) |
-15.2 (2.9)* |
-20.6 (2.9)* |
-19.0 (3.1)** |
-20.7 (3.2)* |
|
WPAI-SHP: Activity Impairmentb |
-5.8 (2.2) |
-8.1 (2.5) |
-11.5 (2.3) |
-16.3 (2.3)* |
-18.4 (2.3)** |
-22.6 (2.3)** |
-22.7 (2.3)** |
-26.1 (2.3)** |
|
n (%) |
Placebo (N=92) |
Adalimumab 40 mg Q2W (N=89) |
Ixekizumab 80 mg Q4W (N=100) |
Ixekizumab 80 mg Q2W (N=90) |
||||
|
Week 12 |
Week 24 |
Week 12 |
Week 24 |
Week 12 |
Week 24 |
Week 12 |
Week 24 |
|
|
HAQ-DI MCIDc |
27 (29.3) |
24 (26.1) |
44 (49.4)* |
44 (49.4)** |
49 (49.0)* |
49 (49.0)** |
58 (64.4)** |
52 (57.8)** |
|
*p<.05 vs. PBO; **p≤.001 vs. PBO aThe study was powered only for comparisons between ixekizumab and placebo or adalimumab and placebo. bDecrease in score represents improvement. cIncrease in score represents improvement. cMCID ≥0.35 improvement from baseline; only patients with a baseline HAQ-DI score ≥0.35 were included in the analysis. EQ-5D VAS, European Quality of Life 5 Dimensions Visual Analog Scale; HAQ-DI, Health Assessment Questionnaire – Disability Index; MCID, Minimal Clinically Important Difference; SF-36 PCS, Short Form-36 Health Survey Physical Component Score; WPAI‑SHP, Work Productivity and Activity Impairment-Specific Health Problem. |
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To cite this abstract in AMA style:
Gottlieb AB, Mease PJ, Cuchacovich RS, Shuler CL, Lin CY, Burge RT, Samanta S, Lee CH, Gladman DD. Ixekizumab Improves Physical Function, Quality of Life, and Work Productivity in Biologic Disease-Modifying Antirheumatic Drug-Naive Patients with Active Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/ixekizumab-improves-physical-function-quality-of-life-and-work-productivity-in-biologic-disease-modifying-antirheumatic-drug-naive-patients-with-active-psoriatic-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/ixekizumab-improves-physical-function-quality-of-life-and-work-productivity-in-biologic-disease-modifying-antirheumatic-drug-naive-patients-with-active-psoriatic-arthritis/