Session Information
Date: Sunday, October 21, 2018
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Ixekizumab (IXE), an IL-17A antagonist, was shown to be superior to placebo (PBO) in inhibiting the progression of structural joint damage in patients (pts) with PsA treated for 24 weeks (wks).1 We assessed the progression of structural joint damage in PsA patients with IXE for up to 3 years
Methods: SPIRIT-P1 (NCT01695239) is a Phase 3 clinical trial investigating IXE treatment in biologic DMARD-naïve pts with active PsA. Pts must have had ≥1 joint erosion on the hand and foot radiographs confirmed by central reading or had a C reactive protein level >6 mg/L at screening. 417 pts were randomized to 80 mg IXE every 2 (Q2W; N=103) or 4 wks (Q4W; N=107) following a 160 mg initial dose, PBO (N=106), or 40 mg adalimumab Q2W (ADA; active reference arm; N=101) for 24 wks. PBO and ADA pts were re-randomized (1:1) to IXEQ2W or IXEQ4W at Wk 16 (inadequate responders) or 24. Analyses are presented for either only pts who entered the long-term extension (LTE; wks 52-156) or were intent-to-treat (ITT; wks 0-156). Radiographs were scored independently by 2 readers blinded to timepoint and clinical data. All pts were assessed for structural joint damage using the van der Heijde modified PsA Total Sharp Score (mTSS, 0-528 scale, average of readers). For LTE patients, data is presented as linear extrapolation or as observed. For linear extrapolation, any missing post-baseline data were imputed if pts had a baseline and ≥1 post-baseline value (i.e. Wk 52, 108, or 156). For ITT patients, post-hoc data is presented from a mixed model for repeated measures (MMRM).
Results: Of pts initially randomized (N=417), 300 pts (72%) entered the LTE (Wks 52-156) and 243 pts completed SPIRIT-P1 (58%). Adverse events and lack of efficacy were the primary reasons for discontinuation. 260 LTE pts had radiographs. Of LTE pts, mean mTSS change from baseline values at Wk 52, 108, and 156 for all 6 treatment groups are presented (Table). Wk 156 mean (SD) mTSS change from baseline values (linear extrapolation) were 1.7 (6.6) and 1.0 (3.2) for pts initially randomized to IXEQ4W and IXEQ2W. The Wk 156 cumulative probability plot is presented (Figure 1). For ITT patients, Wk 156 least squares mean (SE) mTSS change from baseline values (MMRM) were 1.9 (0.4) and 0.9 (0.4) for pts initially randomized to IXEQ4W and IXEQ2W. For LTE pts initially randomized to IXE, the majority of pts had Wk 156 mTSS change from baseline values (linear extrapolation) ≤0 (IXEQ4W: 67%; IXEQ2W: 62%) or ≤0.5 (IXEQ4W: 74%; IXEQ2W: 70%).
Conclusion: Over a 3 year period, minimal changes in mTSS were observed in the majority of PsA pts treated with IXEQ2W or IXEQ4W.
1. Mease P et al. 2017 ARD 76(1):79
|
Table. Radiographic Progression of Structural Joint Damage (Long-Term Extension Population) |
||||||
|
|
PBO/ IXEQ4W (N=31) |
PBO/ IXEQ2W (N=33) |
ADA/ IXEQ4W (N=39) |
ADA/ IXEQ2W (N=35) |
IXEQ4W/ IXEQ4W (N=81) |
IXEQ2W/ IXEQ2W (N=81) |
|
Baseline (Week 0), Mean (SD) |
||||||
|
mTSS |
9.6 (11.0) |
28.6 (42.4) |
18.1 (28.2) |
18.3 (32.7) |
19.7 (33.1) |
15.7 (31.4) |
|
mTSS, Change from Baseline, Mean (SD), Linear Extrapolationa |
||||||
|
Week 52 |
Nx=26 0.2 (0.6) |
Nx=29 0.9 (1.9) |
Nx=34 0.1 (1.0) |
Nx=32 -0.1 (2.4) |
Nx=72 0.6 (2.3) |
Nx=65 0.3 (1.5) |
|
Week 108 |
Nx=27 0.4 (0.8) |
Nx=29 1.2 (2.1) |
Nx=34 0.3 (1.3) |
Nx=32 0.4 (3.3) |
Nx=72 1.1 (4.1) |
Nx=66 0.6 (2.1) |
|
Week 156 |
Nx=27 0.6 (1.3) |
Nx=29 1.4 (2.5) |
Nx=34 0.3 (1.4) |
Nx=32 0.5 (3.6) |
Nx=72 1.7 (6.6) |
Nx=66 1.0 (3.2) |
|
mTSS, Change from Baseline, Mean (SD), Observed |
||||||
|
Week 52 |
n=26 0.2 (0.6) |
n =29 0.9 (1.9) |
n=34 0.1 (1.0) |
n=32 -0.1 (2.4) |
n=72 0.6 (2.3) |
n=65 0.3 (1.5) |
|
Week 108 |
n=27 0.4 (0.8) |
n=29 1.2 (2.1) |
n=33 0.3 (1.3) |
n=32 0.4 (3.3) |
n=69 1.2 (4.2) |
n=66 0.6 (2.1) |
|
Week 156 |
n=25 0.5 (1.2) |
n=28 1.4 (2.6) |
n=30 0.2 (1.3) |
n=28 0.6 (3.8) |
n=60 1.6 (7.1) |
n=61 1.0 (3.3) |
|
Percentage of Non-Progessors in mTSS at Week 156, n (%), Linear Extrapolationa |
||||||
|
mTSS change ≤0 |
Nx=27 20 (74%) |
Nx=29 13 (45%) |
Nx=34 27 (79%) |
Nx=32 23 (72%) |
Nx=72 48 (67%) |
Nx=66 41 (62%) |
|
mTSS change ≤0.5 |
Nx=27 22 (82%) |
Nx=29 17 (59%) |
Nx=34 30 (88%) |
Nx=32 24 (75%) |
Nx=72 53 (74%) |
Nx=66 46 (70%) |
|
mTSS change ≤1.85 |
Nx=27 23 (85%) |
Nx=29 20 (69%) |
Nx=34 32 (94%) |
Nx=32 27 (84%) |
Nx=72 60 (83%) |
Nx=66 56 (85%) |
|
N=patients entering the long-term extension period (Weeks 52-156); Nx= patients with non-missing change from baseline mTSS after linear extrapolation; n=patients with change from baseline mTSS; SD=standard deviation aMissing mTSS data were imputed using a linear extrapolation if patients had a baseline and at least 1 post-baseline value (i.e. Week 52, 108, or 156). 0% were linear extrapolated at Week 52, 1.5% at Week 108, and 10.8% at Week 156. |
||||||
To cite this abstract in AMA style:
van der Heijde D, Chandran V, Fleischmann R, Benichou O, Rathmann S, Shuler C. Radiographic Progression of Structural Joint Damage in Patients with Active Psoriatic Arthritis Treated with Ixekizumab for up to 3 Years [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/radiographic-progression-of-structural-joint-damage-in-patients-with-active-psoriatic-arthritis-treated-with-ixekizumab-for-up-to-3-years/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/radiographic-progression-of-structural-joint-damage-in-patients-with-active-psoriatic-arthritis-treated-with-ixekizumab-for-up-to-3-years/