Session Information
Date: Tuesday, October 23, 2018
Title: Spondyloarthritis Including Psoriatic Arthritis – Clinical Poster III: Treatment
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets IL-17A, was superior to placebo (PBO) at Week (Wk) 24 for treating PsA signs and symptoms in patients (pts) with active PsA and prior inadequate response or intolerance to TNF inhibitors (TNFi) (Nash et al. Lancet, 2017). We report efficacy and safety results of IXE following 2 years of treatment in SPIRIT-P2.
Methods: Adult subjects (N=363) who met Classification for PsA (CASPAR) criteria with active PsA and inadequate response or intolerance to TNFi were randomized 1:1:1 to 80 mg IXE every 4 wks (Q4W, N=122) or 2 wks (Q2W, N=123) following a 160-mg starting dose of IXE at Wk 0 or PBO (N=118). Pts randomized to PBO were re-randomized 1:1 to IXE Q2W or Q4W at either Wk 16 if inadequate responders (<20% improvement in both tender joint count [TJC] and swollen joint count [SJC]) or Wk 24. From Wk 32, pts were discontinued from the study if they had <20% improvement in both TJC and SJC. Efficacy outcomes were ACR20/50/70 response, Psoriasis Area and Severity Index (PASI) 75/90/100 response, Leeds Enthesitis Index (LEI), Leeds Dactylitis Index-Basic (LDI-B), Minimal Disease Activity (MDA), and HAQ-Disability Index (DI). Ad-hoc efficacy analysis for the combined treatment periods from Wk 0-108 included pts initially randomized to IXE. Missing values were imputed by modified nonresponder imputation (mNRI) for categorical data or modified baseline observation carried forward (mBOCF) for continuous data. Safety analyses included all available safety data at the time of Wk 108 database lock for pts receiving ≥1 dose of IXE and was summarized as incidence rates (IR) per 100 pt-years.
Results: Overall, 54.2% of randomized pts completed 108 wks of treatment. Wk 108 responses (mNRI) for pts initially randomized to IXE Q4W or IXE Q2W, respectively, were 59.6% and 47.9% for ACR20, 33.2% and 27.8% for MDA, 65.1% and 48.3% for PASI 75, 45.5% and 37.5% for LEI=0, and 63.0% and 60.0% for LDI-B=0; mean (SD) change from baseline (mBOCF) in HAQ-DI was -0.4 (0.5) for IXE Q4W and -0.4 (0.6) for IXE Q2W. IRs of treatment-emergent adverse event (AE) are provided in the table below; most were mild or moderate in severity. Serious AE IRs were 5.8 (IXE Q4W) and 7.7 (IXE Q2W). Three deaths occurred; causes of death were myocardial infarction (IXE Q2W/IXE Q2W), metastatic renal cell carcinoma (IXE Q4W/IXE Q4W), and cardiopulmonary arrest (PBO/IXE Q2W).
Conclusion: IXE provided clinically meaningful and sustained improvement in PsA signs and symptoms for up to 2 years of treatment among pts with prior inadequate response or intolerance to TNFi, consistent with responses during earlier treatment periods of SPIRIT-P2. No unexpected safety outcomes were reported and the safety profile was consistent with the IXE Phase 3 program in pts with active PsA and with moderate-to-severe plaque psoriasis.
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Table. Efficacy and Safety Outcomes at Week 108 of SPIRIT-P2 |
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Efficacy (Intent-to-Treat—Patients Randomized to IXE at Week 0) |
IXE Q4W N=122 |
IXE Q2W N=123 |
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Response rate (mNRI), n/Nx (%) |
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ACR20 |
73/122 (59.6) |
59/123 (47.9) |
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ACR50 |
56/121 (46.2) |
40/123 (32.5) |
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ACR70 |
28/122 (23.2) |
27/121 (22.6) |
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MDAa |
41/122 (33.2) |
34/123 (27.8) |
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LEI=0b |
31/68 (45.5) |
32/84 (37.5) |
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LDI-B=0c |
17/27 (63.0) |
12/20 (60.0) |
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PASI 75d |
44/68 (65.1) |
33/68 (48.3) |
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PASI 90d |
38/68 (55.3) |
27/68 (40.3) |
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PASI 100d |
27/68 (39.0) |
24/68 (35.3) |
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Change from baseline (mBOCF), mean (SD) |
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|
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Baseline HAQ-DI total score |
1.2 (0.6) |
1.2 (0.6) |
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HAQ-DI, change from baseline |
Nx=101 -0.4 (0.5) |
Nx=103 -0.4 (0.6) |
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Safetye (All Patients Receiving ≥1 Dose of IXE) |
Total IXE Q4W N=168 |
Total IXE Q2W N=169 |
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Number of Events, n (IR) |
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|
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Total patient-years |
308.7 |
271.5 |
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Treatment-emergent adverse eventsf |
150 (48.6) |
150 (55.3) |
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Mild |
92 (29.8) |
81 (29.8) |
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Moderate |
93 (30.1) |
89 (32.8) |
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Severe |
14 (4.5) |
28 (10.3) |
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Discontinuations due to adverse event |
15 (4.9) |
20 (7.4) |
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Serious adverse events |
18 (5.8) |
21 (7.7) |
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Death |
1 (0.3) |
2 (0.7) |
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Adverse events of special interest |
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|
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Serious infections |
5 (1.6) |
4 (1.5) |
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Allergic reactions/hypersensitivities |
16 (5.2) |
15 (5.5) |
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Anaphylaxis |
0 |
0 |
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Injection site reactions |
28 (9.1) |
43 (15.8) |
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Malignancies |
6 (1.9) |
1 (0.4) |
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Inflammatory bowel disease |
1 (0.3) |
0 |
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aMDA response is defined as fulfilling at least 5 of 7 MDA criteria: TJC ≤1, SJC ≤1, PASI ≤1 (or body surface area ≤3%), Patient pain VAS ≤15, patient global disease activity VAS ≤20, HAQ-DI ≤0.5, and tender entheseal points ≤1. bPatients with baseline enthesitis (LEI >0). cPatients with baseline dactylitis (LDI-B >0). dPatients with baseline psoriasis body surface area involvement ≥3%. eIncludes all available safety data at the time of Week 108 database lock; baseline for safety analysis was defined as the time of first IXE injection. fPatients with multiple occurrences of the same event were counted under the highest severity category. Abbreviations: IR, incidence rate per 100 total patient-years; IXE Q2W, ixekizumab 80 mg every 2 weeks; IXE Q4W, ixekizumab 80 mg every 4 weeks; LDI-B, Leeds Dactylitis Index-Basic; LEI, Leeds Enthesitis Index; mBOCF, modified baseline observation carried forward; MDA, Minimal Disease Activity; mNRI, modified nonresponder imputation; n, number of patients who met criteria; Nx, number of patients in the specified analysis population; PASI, Psoriasis Area and Severity Index; SJC, swollen joint count; TJC, tender joint count; VAS, visual analog scale. |
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To cite this abstract in AMA style:
Orbai AM, Gellett AM, Kerr L, Constantin A. Efficacy and Safety of Ixekizumab in Patients with Active Psoriatic Arthritis and Previous Inadequate Response to TNF Inhibitors: Two-Year Follow-up from a Phase 3 Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-ixekizumab-in-patients-with-active-psoriatic-arthritis-and-previous-inadequate-response-to-tnf-inhibitors-two-year-follow-up-from-a-phase-3-study/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-ixekizumab-in-patients-with-active-psoriatic-arthritis-and-previous-inadequate-response-to-tnf-inhibitors-two-year-follow-up-from-a-phase-3-study/