Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: IL-23 may be implicated in spondylitis. A substantial number of pts with spondylitis and peripheral joint involvement were enrolled in PSUMMIT. We evaluated the efficacy of SC UST 45/90 mg in a subgroup of psoriatic arthritis (PsA) pts with physician diagnosed spondylitis and peripheral joint involvement through wk108, from PSUMMIT 1.
Methods: Adult PsA patients (n=615) with active disease (≥5 SJC and ≥5 TJC;CRP≥0.3mg/dL) despite DMARD and/or NSAIDs were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks. Pts treated with prior anti-TNF agents were excluded. Stable concomitant MTX was permitted but not mandated. At wk16, pts with <5% improvement in TJC & SJC entered blinded early escape (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). PBO pts subsequently crossed over to UST45mg at wk24. Pts received q12w dosing to wk88, with final efficacy evaluation at wk100 and safety assessment at wk108. Pts with spondylitis and peripheral joint involvement as their primary arthritis presentation of PsA also had BASDAI assessments at wks12 and 24.
Results: 186 randomized pts (70 PBO, 116 UST combined) had spondylitis with peripheral joint involvement at baseline (30% of overall population); mean baseline characteristics were similar to the overall population (age 45.6yrs, weight 82.8kg, PsA duration 6.3yrs, SJC/TJC 14.3/24.1, HAQ-DI 1.3; BASDAI 6.5, and 26% were HLAB27 positive. Mean baseline scores among pts with dactylitis (n=100), enthesitis (148), and skin disease (147) were 8.3, 5.6, and PASI 14.2, respectively. At wk24, greater proportions of combined UST45/90mg treated pts had improvements in dactylitis/enthesitis measurements, HAQ-DI and ACR20/50/70 responses than PBO (Table). Clinical improvements were generally maintained through wk100. A significantly higher proportion of UST-treated pts achieved BASDAI20/50/70 responses vs. PBO at wk24 (54.1%/27.9%/14.4% vs. 26.2%/13.1%/0.0%). Peripheral structural damage assessed by total vdH-S mean change from baseline also showed improvement in the UST groups vs PBO at wk24. Of the 135 patients with ≥3% BSA involvement and spondylitis with peripheral arthritis at baseline, PASI75 responses were also maintained through wk100. During the PBO-controlled period , the proportion of pts with AEs were comparable between the PBO and combined UST-treated groups (AEs 32.9% vs 24.1%; SAEs 1.4% vs 0.9%; discontinuations due to AEs 2.9% vs 0.9%; serious infections 14.3% vs 7.8%). Through 2yrs, safety observations were consistent with the overall PsA population.
Conclusion: In this post-hoc subgroup analysis, UST significantly improved signs and symptoms, and demonstrated improvements in BASDAI and peripheral radiographic progression compared with PBO through wk24; efficacy was maintained through wk100. UST was well-tolerated and demonstrated a safety profile similar to that observed in the overall PsA study population.
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Table: PSUMMIT 1-Efficacy Outcomes in Patients with Spondylitis and Peripheral Joint Involvement at Baseline (BL) |
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|
Wk 24 |
Wk 52 |
Wk 100 |
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|
|
PBO |
UST Combined |
PBO→ 45mg |
UST Combined |
PBO→ 45mg |
UST Combined |
|
n |
70 |
116 |
63 |
116 |
63 |
116 |
|
ACR20 /ACR50/ ACR70 (%) |
20.0/2.9/1.4 |
38.8t/26.7/12.1 tP=0.006 |
N=63 65.1/41.3/15.9 |
N=111 62.2/36.9/21.6 |
N=62 62.9/35.5/16.1 |
N=109 61.5/43.1/22.9 |
|
Mean % change (median) from BL entheses score (MASES index)* |
N=50 -5.81(0.00) |
N=92 -46.14(-48.33) P=0.009 |
N=48 -53.88(-100.00) |
N=88 -58.39(-88.31) |
N=47 -50.70(-100.00) |
N=87 -49.58(-100.00) |
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Mean % change(median) from BL dactylitis score** |
N=33 2.47(0.00) |
N=63 -64.05(-94.44) P<0.001 |
N=31 -65.38(-100.00) |
N=62 -75.58(-100.00) |
N=31 -73.66(-100.00) |
N=61 -81.15(-100.00) |
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Mean (SD) change from BL HAQ-DI |
N=70 -0.10(0.41) |
N=116 -0.36(0.56) P<0.001 |
N=63 -0.42(0.39) |
N=111 -0.41(0.58) |
N=62 -0.38(0.48) |
N=109 -0.39(0.63) |
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PASI 75 response *** |
N=52 11.5% |
N=95 65.3% P<0.001 |
N=47 66.0% |
N=92 73.9% |
N=44 63.6% |
N=91 78.0% |
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Total vdH-S mean change from BL (peripheral joints) |
1.92(7.26) |
0.05(1.77) P<0.001 |
2.03(10.15) |
0.34(2.41) |
4.28(21.03) |
1.46(5.07) |
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Patients who did not receive UST are excluded at wk52 and wk100; *Enthesitis with spondylitis and peripheral joint involvement at baseline; **Dactylitis with spondylitis and peripheral joint involvement at baseline; ***Among randomized patients with ≥3% BSA psoriasis skin, spondylitis and peripheral joint involvement at BL |
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Disclosure:
A. Kavanaugh,
AbbVie,
2,
Amgen,
2,
Roche Pharmaceuticals,
2,
Pfizer Inc,
2,
Janssen Pharmaceutica Product, L.P.,
2,
UCB,
2,
BMS,
2,
Astellas,
2;
L. Puig Sanz,
Abbott, Amgen, Celgene, Janssen Research & Development, LLC., Merck/Schering-Plough, and Pfizer,
2;
A. B. Gottlieb,
Amgen, Astellas, Akros, Celgene, BMS, Beiesrdorf, AbbVie,Janssen, TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor, Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Life, GSK, Xenoport, Catabasis, Sanofi Ave,
5,
Janssen, Amgen, AbbVie, Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck,
2;
C. T. Ritchlin,
Amgen, Janssen, and UCB ,
2,
Abbott, Amgen, Janssen, Regeneron, Roche, and UCB,
5;
Y. You,
Janssen Research & Development, LLC.,
3;
Y. Wang,
Janssen Research & Development, LLC.,
3;
A. M. Mendelsohn,
Janssen Research & Development, LLC.,
3;
M. Song,
Janssen Research & Development, LLC.,
3;
P. Rahman,
Abbott, Amgen, Janssen, Merck/Schering-Plough, and Wyeth,
2;
I. B. McInnes,
Consulting fees from Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene and Lilly,
5.
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