Session Information
Date: Tuesday, November 10, 2015
Title: Spondylarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment Poster III: Therapy
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose:
Anti‒TNFs are the only biologics currently approved for ankylosing spondylitis (AS). There is a significant unmet need in those patients (pts) with an inadequate response/intolerance to these agents. The efficacy and safety of secukinumab, an anti–interleukin-17A monoclonal antibody, has been assessed in two Phase 3 studies in pts with active AS, MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375).1,2 Here, we present the efficacy and safety of secukinumab by anti-TNF history in pts enrolled in these 2 studies.
Methods:
In MEASURE 1, 371 pts were randomized to secukinumab or placebo (PBO). The secukinumab group received 10 mg/kg intravenously (iv) at baseline (BL) and Weeks (Wks) 2 and 4, followed by subcutaneous (sc) 150 (IV→150 mg) or 75 mg (IV→75 mg) every 4 wks (q4w) from Wk 8; PBO was given according to the same dosing schedule. In MEASURE 2, 219 pts were randomized to receive secukinumab 150 or 75 mg sc or PBO at BL, Wks 1, 2, and 3, and q4w starting from Wk 4. Randomization was stratified by anti-TNF history: anti-TNF-naive, or inadequate response/intolerance to not more than one anti-TNF agent (anti-TNF-IR). The primary endpoint for both studies was ASAS20 response at Wk 16. Secondary endpoints were ASAS40, hsCRP, ASAS 5/6, BASDAI, SF-36 PCS, ASQoL, and ASAS partial remission. Wk 16 analyses used non-responder imputation (binary variables) and mixed-model repeated measures (continuous variables). Wk 52 data are as observed. Analysis of primary and secondary endpoints stratified by anti-TNF history was pre-specified.
Results:
At BL, 73% and 61% of pts were anti‒TNF-naïve in MEASURE 1 and MEASURE 2, respectively. Compared with PBO, ASAS20 response rates at Wk 16 were higher with all secukinumab doses, except for the 75 mg sc dose in MEASURE 2, in both anti‒TNF-naïve and anti‒TNF-IR pts (Table). Improvements with secukinumab were observed for all secondary endpoints in anti‒TNF-naïve pts, except ASAS partial remission in MEASURE 2, and for most secondary endpoints in anti‒TNF-IR pts. No incremental increase in efficacy was observed with the IV→150 mg or IV→75 mg doses versus 150 mg sc, despite the greater exposure conferred by iv loading. At Wk 52, 319 (86.0%) pts remained in MEASURE 1 and 181 (82.6%) in MEASURE 2. Clinical responses to secukinumab were sustained or continued to improve through 52 wks of therapy in both anti‒TNF-naïve and anti‒TNF-IR pts (Table). Responses were generally higher in anti-TNF-naïve vs anti–TNF-IR pts. ASAS40 response rates at Wk 52 in anti-TNF-naïve and anti-TNF-IR pts were 67.1% and 45.8% with IV→150 mg, 48.8% and 50.0% with IV→75 mg, 64.1% and 45.5% with 150 mg, and 47.6% and 26.3% with 75 mg.
Conclusion:
Secukinumab 150 mg provided sustained improvements in the signs and symptoms of AS in both anti‒TNF-naïve and anti‒TNF-IR pts.
Reference:
- Baeten D et al. Arthritis Rheumatol 2014; 66 (11Suppl):S360.
- Sieper J et al. Arthritis Rheumatol. 2014;66(11Suppl):S232.
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Table: Efficacy at Week 16a and 52b |
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MEASURE 1 |
MEASURE 2 |
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Secukinumab |
PBO |
Secukinumab |
PBO |
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|
IV→150 mg |
IV→75 mg |
150 mg |
75 mg |
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Anti‒TNF-Naïve |
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ASAS20, % responders
|
Wk 16 |
66.3* |
60.0† |
32.6 |
68.2† |
51.1 |
31.1 |
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|
Wk 52 |
78.5 |
73.8 |
N/A |
82.1 |
71.4 |
N/A |
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ASAS40, % responders
|
Wk 16 |
48.9* |
34.4§ |
15.7 |
43.2‡ |
31.1 |
17.8 |
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|
Wk 52 |
67.1 |
48.8 |
N/A |
64.1 |
47.6 |
N/A |
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BASDAI (Mean change from BL)
|
Wk 16 |
−2.72* |
−2.61* |
−0.72 |
−2.56§ |
−2.27‡ |
−1.15 |
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Wk 52 |
−3.32 |
−2.93 |
N/A |
−3.33 |
−2.86 |
N/A |
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Anti‒TNF-IR |
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ASAS20, % responders |
Wk 16 |
45.5‡ |
58.8† |
18.2 |
50.0‡ |
25.0 |
24.1 |
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Wk 52 |
70.8 |
64.3 |
N/A |
59.1 |
47.4 |
N/A |
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ASAS40, % responders
|
Wk 16 |
21.2 |
29.4‡ |
6.1 |
25.0§ |
17.9‡ |
0.0 |
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Wk 52 |
45.8 |
50.0 |
N/A |
45.5 |
26.3 |
N/A |
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BASDAI (Mean change from BL) |
Wk 16 |
−1.72‡ |
−2.19§ |
−0.65 |
−1.60 |
−1.38 |
−0.59 |
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Wk 52 |
−2.77 |
−2.67 |
N/A |
−2.80 |
−2.13 |
N/A |
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*P<0.0001; †P<0.001; §P<0.01; ‡P<0.05 vs. PBO. aNRI (binary variables) and LS Mean via MMRM (continuous variables) data presented at Wk 16; bObserved data presented at Wk 52; LS, least squares; N/A, not applicable. MEASURE 1: At Wk 16/52, in anti–TNF-naïve pts: secukinumab IV→150 mg, n = 92/79; secukinumab IV→75 mg, n = 90/80 (except for BASDAI at Wk 52 where n = 81); PBO, n = 89/NA; anti–TNF-IR pts: secukinumab IV→150 mg, n = 33/24; secukinumab IV→75 mg, n = 34/28; PBO, n = 33/NA MEASURE 2: At Wk 16/52, in anti–TNF-naïve pts: secukinumab 150 mg, n = 44/39; secukinumab 75 mg, n = 45/42; PBO, n = 45/NA; anti–TNF-IR pts: secukinumab 150 mg, n = 28/22; secukinumab 75 mg, n = 28/19; PBO, n = 29/NA |
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To cite this abstract in AMA style:
Baeten D, Blanco R, Geusens P, Sieper J, Jui-Cheng T, Martin R, Porter B, Richards H. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis in Anti-TNF-Naïve Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-ankylosing-spondylitis-in-anti-tnf-naive-patients-and-those-previously-exposed-to-anti-tnf-therapy-52-week-results-from/. Accessed .« Back to ACR/ARHP Annual Meeting 2015
ACR Meeting Abstracts - https://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-ankylosing-spondylitis-in-anti-tnf-naive-patients-and-those-previously-exposed-to-anti-tnf-therapy-52-week-results-from/