Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Ustekinumab (UST) has demonstrated substantial efficacy and an acceptable safety profile, and is approved for use, in treating moderate-to-severe psoriasis. UST has also demonstrated efficacy in pts with active psoriatic arthritis (PsA) at wk24 in the Phase 3, multicenter, PBO-controlled PSUMMIT2 trial. Results through wk52 PSUMMIT 2 are presented herein.
Methods: 312 adults with active PsA were randomized to UST 45mg or 90mg at wk0, wk4, and q12w or PBO at wks0, 4, and 16 followed by crossover to UST 45mg at wk24, wk28, and wk40. Randomization was stratified by site, weight (≤100kg, >100kg) and baseline MTX use, and pts previously treated with biologic anti-TNF agents were eligible. At wk16, pts with <5% improvement in both tender/swollen joint counts entered blinded early escape (PBO→UST 45mg, 45mg→90mg, 90mg→90mg). The primary endpoint was ACR20 at wk24. Secondary endpoints were HAQ-DI, ACR50, ACR70, and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75).
Results: Anti-TNF-experienced pts had more active disease at baseline than anti-TNF-naïve pts. More UST (43.8%-combined, 43.7%-45mg, 43.8%-90mg) than PBO (20.2%) treated pts had ACR20 at wk24 (all P<0.001). Significant treatment differences were also observed for ACR50 and PASI75 response at wk24 (table). Efficacy was sustained through wk52. At wk52, 51% and 44% of pts who were and were not, respectively, receiving MTX at baseline had ACR20. UST efficacy at wk52 was more robust in anti-TNF-naïve (ACR20 59-73%) than anti-TNF-experienced (37-41%) pts and pts who had previously received 1 (50-55%) vs. 2 (13-39%) or ≥3 (13-30%) anti-TNF agents. UST was generally well tolerated, with no deaths or tuberculosis and similar rates of AEs (78.6%-45mg, 77.9%-90mg), serious AEs (5.8%-45mg, 5.8%-90mg), and AEs leading to discontinuation (5.8%-45mg, 3.8%-90mg) reported across doses through wk60. Two pts, both anti-TNF-experienced, had malignancies (breast cancer-45mg, squamous cell carcinoma-90mg); 2/287 (0.7%) of UST-treated pts (both 90mg) had serious infections. Three pts (2-45mg, 1-90mg) had major adverse cardiovascular events (myocardial infarctions) through wk60, all had multiple cardiovascular risk factors and prior anti-TNF experience.
Conclusion: Both UST doses (45/90 mg q12w) yielded significant and sustained improvements in PsA signs/symptoms with favorable and comparable safety profiles. UST was effective in both anti-TNF-naïve and anti-TNF-experienced pts, with greater efficacy in anti-TNF naïve pts and anti-TNF-experienced pts previously treated with 1 or 2 anti-TNF agents.
|
Table. Summary of efficacy among randomized PsA pts |
||||
|
(N) |
Placebo (104) |
UST 45 mg (103) |
UST 90 mg (105) |
Combined UST (208) |
|
BASELINE |
|
|
|
|
|
Anti-TNF experienced pts |
|
|
|
|
|
Tender(0-68)/swollen(0-66) joints |
24/11 |
24/15 |
26/13 |
25/14 |
|
Physician/Pt global disease (0-10 VAS)/HAQ-DI (0-3) |
7.2/6.1/1.31 |
7.7/6.6/1.44 |
7.6/6.9/1.56 |
7.6/6.8/1.50 |
|
Anti-TNF naïve pts |
|
|
|
|
|
Tender/swollen joints |
20/10 |
19/12 |
19/10 |
19/11 |
|
Physician/Patient global disease/HAQ-DI |
7.0/6.1/1.13 |
6.4/5.7/1.25 |
6.6/5.5/1.06 |
6.6/5.6/1.13 |
|
WEEK 24 EFFICACY |
|
|
|
|
|
ACR20/ACR50/ACR70 |
20.2/6.7/2.9% |
43.7***/17.5*/6.8% |
43.8***/22.9**/8.6% |
43.8***/20.2**/7.7% |
|
PASI751 |
5.0% |
51.3%*** |
55.6%*** |
53.4%*** |
|
WEEK 52 EFFICACY (N) |
Placebo→UST 45 mg, (77) |
UST 45 mg (94) |
UST 90 mg (95) |
Combined UST (189) |
|
ACR20/ACR50/ACR70 |
55.8/28.6/15.6% |
46.8/27.7/12.8% |
48.4/26.3/17.9% |
47.6/27.0/15.3% |
|
ACR20 by baseline MTX use (Yes / No) |
51.2/61.1% |
46.0/47.7% |
56.5/40.8% |
51.0/44.1% |
|
ACR20 – anti-TNF-naïve/exper |
73.0/40.0% |
60.0/37.0% |
58.5/40.7% |
59.3/38.9% |
|
ACR20 by no. of prior anti-TNF agents (1 / 2 / ≥3) |
54.5/12.5/30.0% |
52.4/25.0/29.4% |
50.0/38.9/12.5% |
51.0/32.4/24.0% |
|
% improve dactylitis/enthesitis1 |
33.3/100.0% |
36.7/95.0% |
60.0/90.9% |
50.0/95.0% |
|
PASI752 |
56.1% |
56.5% |
64.4% |
60.6% |
|
*, **, *** indicate p < 0.05, 0.01, 0.001, respectively, versus placebo. Data are reported as % of pts or median. 1Among patients with dactylitis or enthesitis at baseline. 2Among pts with ≥ 3% body surface area psoriasis involvement at baseline (mean PASI scores at baseline were 11.3 for placebo, 13.4 for UST 45 mg, and 12.1 for UST 90 mg). ACR=American College of Rheumatology, HAQ-DI=Health Assessment Questionnaire-Disability Index, PASI=Psoriasis Area and Severity Index, TNF=tumor necrosis factor, UST=ustekinumab, VAS=visual analogue scale |
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Disclosure:
C. T. Ritchlin,
Amgen, Janssen, UCB, Abbott (AbbVie), Regeneron,
5,
Amgen, Janssen, UCB,
2;
I. B. McInnes,
Novartis, Janssen Research & Development, LLC.,
8,
UCB,
9;
A. Kavanaugh,
Janssen Research & Development, LLC.,
9;
L. Puig,
Abbvie, Amgen, Janssen, Lilly, Novartis, Pfizer, VBL,
2,
Celgene, Abbvie, Janssen, Novartis, MSO, Pfizer, Lex Pharma,
5;
P. Rahman,
Amgen, Abbott, BMS, Merck, Pfizer, Janssen, Hoffman-La Roche, UCB, Novartis, Sanofi-Aventis,
5,
Amgen, Abbott, BMS, Merck, Pfizer, Janssen, Hoffman-La Roche, UCB, Novartis, Sanofi-Aventis,
9;
C. Brodmerkel,
Janssen Research & Development, LLC.,
3;
S. Li,
Janssen Research & Development, LLC.,
3;
Y. K. Shen,
Janssen Research & Development, LLC.,
3;
M. K. Doyle,
Janssen Research & Development, LLC.,
3;
A. M. Mendelsohn,
Janssen Research & Development, LLC.,
3;
A. B. Gottlieb,
Janssen, Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia,
2,
Astellas, Janssen, Celgene Corp., Bristol Myers Squibb Co., Beiersdorf, Inc., Abbott Labs. (Abbvie), TEVA, Actelion, UCB, Novo Nordisk, Novartis, Dermipsor Ltd., Incyte, Pfizer, Canfite, Lilly, Coronado, Vertex, Karyopharm, CSL Behring Biotherapies for Li,
5.
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