ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1556

Integrated Safety of Ustekinumab in Psoriatic Arthritis: 2 Year Follow-up from the Psoriatic Arthritis Clinical Development Program

Arthur Kavanaugh1, Iain B. McInnes2, Christopher T. Ritchlin3, Proton Rahman4, Lluís Puig Sanz5, Alice B. Gottlieb6, Michael Song7, Bruce Randazzo7, Shu Li7, Yin You7 and Alan M. Mendelsohn8, 1University of California San Diego, La Jolla, CA, 2University of Glasgow, Glasgow, United Kingdom, 3Allergy Immunology & Rheumatology, University of Rochester Medical Center, Rochester, NY, 4Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada, 5Dermatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 6Tufts Medical Center, Boston, MA, 7Janssen Research & Development, LLC., Spring House, PA, 8Immunology, Janssen Research & Development, LLC., Spring House, PA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Spondyloarthropathies and Psoriatic Arthritis - Clinical Aspects and Treatment II

Session Type: Abstract Submissions (ACR)

Background/Purpose: To report the safety of ustekinumab(UST) from the psoriatic arthritis (PsA)development program.

Methods: Safety data through up to 2yrs of follow-up were pooled from Ph3 for the analysis of overall safety endpoints. Data were pooled from Ph2(n=146) and Ph3 for AEs of interest. In Ph3, adult PsA pts (PSUMMIT I [n=615], PSUMMIT II [n=312]) with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID or previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy (PSUMMIT II only) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks; at wk16, pts with <5% improvement in SJC & TJC entered blinded EE (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). PBO pts crossed over to UST45mg at wks24 and 28 and q12wk dosing. No concomitant DMARDs except MTX (approx 50% in each Ph3 study) were permitted. The PBO-controlled period was 12wks and 16wks for the Ph2 and Ph3 trials, respectively. AEs were reported as the number of events /100 pt-yrs of follow-up (PY). All pts who received ≥1 dose of treatment were included.  

Results: 379 and 1018 pts were treated with PBO and UST, resp, for up to 2yrs(duration of follow-up: Ph2 36wks, PSUMMIT1 108wks, and PSUMMIT2 60wks) with 145 PY and 1403 PY overall for the PBO and UST grps, resp. At baseline, 96.8% were white, 52.2% male, mean age 47.6yrs(SD 11.8). Mean BMI was 30.9 kg/m2(SD 7.1), mean PsA and PsO duration was 7.2 yrs(SD 7.7) and 15.8yrs (SD 12.6), resp. Safety outcomes are detailed in Table 1. Event rates of overall AEs, infections, and SAEs, were comparable among PBO and UST during the PBO-controlled period; rates remained comparable through 2yrs of follow-up. Rates of AEs leading to d/c were higher in PBO. Overall AE rates were not impacted by baseline MTX or prior anti-TNF usage. 1 squamous cell carcinoma (90mg), 1 serious infection (PBO) and 1 MI (PBO) were reported during PBO-controlled period. With up to 2yrs of follow-up, rate of infections was similar in 90mg vs 45mg grps; serious infections were numerically greater in the 90mg vs 45 mg grp(2.1/100PY [95% CI:1.1,3.5] vs 0.5/100PY [95% CI: 0.1,1.3], resp), and included 2 pts in the 90mg grp with multiple events(most were single events without apparent trend). 4 non-melanoma skin cancers (NMSC)(0.64/100PY) occurred in the 90mg grp and no NMSCs occurred in the 45mg grp. 3 malignancies(0.4/100PY), other than NMSC, occurred in 45mg grp and none in 90mg grp. Major adverse cardiovascular event(MACE) rates were low and no dose effects were observed(1.15 vs 0.24 for 45mg and 90mg, resp). No cases of active TB or serious opportunistic infections, RPLS, demyelination, anaphylaxis or serum sickness-like reactions were reported.

Conclusion: Pooled safety data show that UST was well tolerated at both doses with up to 2yrs of follow-up without  new safety signals. The safety profile of UST in the PsA clinical development program was generally comparable to that observed in the psoriasis population.

 

Table 1: Adverse Events Rates per 100 PY of Follow-up (95% CI)

 

PBO-Controlled Period (16 weeks)

 

Through 2 years

 

PBO

 

UST 45mg

UST 90mg

PBO→45mg

UST 45mg

UST 90mg

aOverall AEs

 

Pts treated (n)

309

308

 

308

269

308

308

Pt-yrs of follow-up

94

96

 

95

348

489

491

AEs

314.3

(279.5,352.3)

333.5

(297.9,372.2)

 

378.6

(340.5,419.9)

134.0

(122.1,146.7)

217.8

(205.0,231.3)

202.0

(189.6,215.0)

Infections

101.2

(81.9, 123.8)

84.7

(67.3, 105.3)

 

97.03

(78.2,119.0)

45.4

(38.6,53.1)

61.6(54.8,68.9)

66.4(59.4,74.1)

AEs leading to d/c

11.9

(5.9, 21.2)

3.2

(0.6,9.2)

 

4.2

(1.2,10.9)

1.4

(0.5,3.4)

 3.5(2.0,5.6)

2.5(1.3,4.3)

Serious AE

11.7

(5.8, 21.0)

4.2

(1.1,10.7)

8.4(3.6,16.6)

6.3

(4.0,9.6)

8.2(5.8,11.1)

9.2(6.7,12.3)

Deaths

0

0

0

0

0

 

0

bAEs of Interest        

 

 

PBO

UST 45mg

UST 90mg

PBO

UST 45mg

UST 90mg

Pts treated (n)

379

308

384

379

577

497

Pt-yrs of follow-up

110

96

113

145

773

631

Serious infxns

0.9(0.0,5.0)

0.0(0.0,3.1)

0.0(0.0,2.6)

0.7(0.0,3.8)

0.5(0.1,1.3)

2.1(1.1,3.5)

NMSC

0.0(0.0,2.7)

0.0(0.0,3.1)

0.9(0.0,4.9)

0.0(0.0,2.0)

0.0(0.0,0.4)

0.6(0.2,1.6)

Other malignancies

0.0(0.0,2.7)

0.0(0.0,3.1)

0.0(0.0,2.6)

0.0(0.0,2.1)

0.4(0.1,1.1)

0.0(0.0,0.5)

MACE

0.9(0.0,5.0)

0.0(0.0,3.1)

0.0(0.0,2.6)

0.7(0.0,3.8)

1.0(0.4,2.0)

0.3(0.0,1.2)

aOverall AEs: Ph3 trials (PSUMMIT I&II); Analyzed by dose randomized

bAEs of interest: Ph2 and Ph3 trials (PSUMMIT I&II); b PBO EE and crossover pts were included in the UST 45mg column after EE at wk16 or crossover at wk24. Pts who were dose escalated from 45mg to 90mg were switched to the 90mg column following dose escalation

 

 

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;

I. B. McInnes,

Consulting fees from Novartis, Amgen, Janssen, BMS, Pfizer, UCB, Abbvie, Celgene and Lilly,

5;

C. T. Ritchlin,

Amgen, Janssen, and UCB ,

2,

Abbott, Amgen, Janssen, Regeneron, Roche, and UCB,

5;

P. Rahman,

Abbott, Amgen, Janssen, Merck/Schering-Plough, and Wyeth,

2;

L. Puig Sanz,

Abbott, Amgen, Celgene, Janssen Research & Development, LLC., Merck/Schering-Plough, and Pfizer,

2;

A. B. Gottlieb,

Amgen Inc., Astellas, Akros, Centocor (Janssen), Inc. 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, Karyopha,

5,

Amgen Inc., Astellas, Akros, Centocor (Janssen), Inc. 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, Karyopha,

9,

Centocor (Janssen), Amgen, Abbott (Abbvie), Novartis, Celgene, Pfizer, Lilly, Coronado, Levia, Merck,

2;

M. Song,

Janssen Research & Development, LLC.,

3;

B. Randazzo,

Janssen Research & Development, LLC.,

3;

S. Li,

Janssen Research & Development, LLC.,

3,

Johnson & Johnson,

1;

Y. You,

Janssen Research & Development, LLC.,

3;

A. M. Mendelsohn,

Janssen Research & Development, LLC.,

3.

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