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:
Anti-drug antibody (ADA) development can potentially affect the efficacy of biologics; concomitant MTX decreases the development of ADA for some biologics.1 Ixekizumab (IXE), a mAb that selectively targets IL-17A, may be used with or without MTX. In IXE-treated patients (pts) with active PsA, we evaluated whether ADA development was affected by concomitant MTX or had an effect on long-term efficacy.
Methods:
Two Phase 3 randomized, double-blind, placebo-controlled clinical trials evaluated IXE treatment in adult pts with PsA who were biologic-naive (SPIRIT-P1; NCT01695239) or inadequate responders/intolerant to TNF inhibitors (SPIRIT-P2; NCT02349295). Study details were published2,3; all pts met the Classification Criteria for PsA. Pts received placebo or 80 mg IXE every 2 weeks (Wks; Q2W) or 4 Wks (Q4W) after a 160- mg loading dose. Pts continued stable concomitant conventional DMARDs through Wk 24 (except inadequate responders at Wk 16 who received rescue therapy). Analyses included ADA evaluable pts initially randomized to IXE. ADA, titer, and neutralizing antibody (NAb) status were stratified by MTX use (Integrated data). ACR20 responses stratified by ADA and NAb status were analyzed for SPIRIT-P1 and -P2, separately. Missing values were imputed by non-responder imputation for ACR20 and last observation carried forward for ADA titer.
Results:
Of 223 pts treated with concomitant MTX, 96 (89.7%) of IXE Q4W and 110 (94.8%) of IXE Q2W were ADA negative (-); 11 (10.3%) of IXE Q4W and 6 (5.2%) of IXE Q2W were ADA positive (+). Similarly, of 222 pts without concomitant MTX, 103 (88%) of IXE Q4W and 96 (91.4%) of IXE Q2W were ADA-; 14 (12.0%) of IXE Q4W and 9 (8.6%) of IXE Q2W were ADA+. The majority of ADA+ pts had low titer ADA. The table shows ADA, titer, and NAb status stratified by MTX use. The proportion of SPIRIT-P1 pts achieving ACR20 at Wk 52 when ADA- was 63.8% (n=60) of IXE Q4W and 66.7% (n=60) of IXE Q2W, and when ADA+ was 50.0% (n=6) of IXE Q4W and 54.5% (n=6) of IXE Q2W. The proportion of SPIRIT-P2 pts achieving ACR20 response at Wk 52 when ADA- was 57.1% (n=60) of IXE Q4W and 50.9% (n=59) of IXE Q2W, and when ADA+ was 92.3% (n=12) of IXE Q4W and 50.0% (n=2) of IXE Q2W (Figure).
Conclusion:
The absolute number of ADA+ pts with IXE was relatively small and the majority were low titer. The presence of ADA did not affect the long-term efficacy of IXE in PsA pts. Concomitant MTX did not appear to have a meaningful effect on ADA development.
References:
1. Lecluse LLA et al. Arch Dermatol. 2010;146(2):127–132.
2. Mease PJ et al. Ann Rheum Dis. 2016;0:1-9.
3. Nash P et al. Lancet. 2017;76:79-87.
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Table. Immunogenicity Incidence in SPIRIT-P1 and -P2 (Integrated) by TE-ADA Status and by Presence of |
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Yes: Concomitant MTX |
No: Concomitant MTX |
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IXE Q4W (N=110) |
IXE Q2W (N=118) |
IXE Q4W (N=119) |
IXE Q2W (N=107) |
|
|
ADA evaluable, Nx |
107 |
116 |
117 |
105 |
|
TE-ADA negative, n (%) |
96 (89.7%) |
110 (94.8%) |
103 (88.0%) |
96 (91.4%) |
|
TE-ADA positive, n (%) |
11 (10.3%) |
6 (5.2 %) |
14 (12.0%) |
9 (8.6%) |
|
TE-ADA positive titer status, n (%) |
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|
Low titer |
10 (9.3) |
6 (5.2%) |
12 (10.3%) |
8 (7.6) |
|
Moderate titer |
0 |
0 |
2 (1.7%) |
1 (1.0%) |
|
High titer |
1 (0.9%) |
0 |
0 |
0 |
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TE-ADA positive NAb Status, n (%) |
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NAb positive |
5 (4.7%) |
3 (2.6%) |
6 (5.1%) |
4 (3.8%) |
|
NAb negative |
3 (2.8%) |
0 |
1 (0.9%) |
1 (1.0%) |
|
NAb inconclusive |
3 (2.8%) |
3 (2.6%) |
7 (6.0%) |
4 (3.8%) |
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Abbreviations: ADA=anti-drug antibody; IXE Q4W = ixekizumab 80 mg Q4W; IXE Q2W = ixekizumab 80 mg Q2W; IXE = ixekizumab; N = number of patients in the subgroup of the PsA safety population; Nx = number of ADA- evaluable patients (patients with baseline ADA sample and ≥1 evaluable post-baseline sample or no baseline ADA sample but all post-baseline samples are negative); n = number of patients within the specific category who were ADA Positive/Negative; TE-ADA = treatment-emergent anti-drug antibody |
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To cite this abstract in AMA style:
Ritchlin CT, Merola JF, Gellett AM, Lin CY, Muram T. Anti-Drug Antibodies, Efficacy, and Impact of Concomitant Methotrexate in Ixekizumab-Treated Patients with Psoriatic Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-drug-antibodies-efficacy-and-impact-of-concomitant-methotrexate-in-ixekizumab-treated-patients-with-psoriatic-arthritis/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-drug-antibodies-efficacy-and-impact-of-concomitant-methotrexate-in-ixekizumab-treated-patients-with-psoriatic-arthritis/