prova

Title Poster Background Objectives Methods Results Limitation Conclusions References

Next

P3336

The Ustekinumab Safety Experience in Patients with Moderate-to-severe Psoriasis: Results from Pooled Analyses of Phase 2 and Phase 3 Clinical Trial Data

K. Gordon,1 C. Leonardi,2 N. Yeilding,3 K. Reich4

1Division of Dermatology, NorthShore University Health Systems and the University of Chicago, Evanston, IL; 2Central Dermatology, St. Louis, MO; 3Centocor Research & Development, Inc., Malvern, PA; 4Dermatologikum Hamburg, Hamburg, Germany

This study was supported by Centocor Ortho Biotech, Inc.

68th Annual Meeting Am Acad Dermatol March 5-9, 2010 Miami, Florida, USA


Previous Next

Background

Ustekinumab is a human, monoclonal antibody that binds to the shared p40 subunit of interleukins 12 and 23 and, therefore, inhibits binding to their receptors. In Phase 2 and Phase 3 (PHOENIX 1 and 2) psoriasis studies, ustekinumab therapy has been shown to be highly efficacious in treating patients with moderate to severe psoriasis with a favor-able benefit/risk profile.1,2,3

Objectives

To analyze the cumulative safety experience with up to 76 weeks of treatment (referred �

to as the 1.5-Year Safety Analysis) with ustekinumab across Phase 2 and 3 psoriasis clinical trials

To analyze selected adverse events of interest (i.e., serious infections, malignancies �

and cardiovascular events) in recently locked data with up to 152 weeks of treatment (referred to as the 3-Year Safety Analysis)

Methods

To evaluate the safety of ustekinumab in the overall psoriasis clinical development �

program, safety data was pooled data across psoriasis Phase 2 and Phase 3 stud-ies on two separate occasions based on all data available at the time of the analyses (referred to as 1.5-Year Safety Analyses and 3-Year Safety Analyses).

The 1.5-Year Safety Analyses (n=2266) occurred based on all data available in data- �

base locks that occurred through October 2007, including:

36 weeks of data from the C0379T04 placebo-controlled Phase 2 trial —

76 weeks of data from the PHOENIX 1 placebo-controlled Phase 3 trial —


The 3-Year Safety Analyses (n=3117) occurred based on all data available in data- �

base locks that occurred through May 2009, including:




64 weeks of data from the ACCEPT Phase 3 trial comparing ustekinumab and —etanercept safety and efficacy

Cumulative safety was evaluated during the placebo-controlled period (12- 20 weeks), �

with up to 1.5 years of treatment, and with up to 3 years of treatment. Serious infec-tions and infections requiring antibiotics, malignancies, and major adverse cardiovas-cular events were evaluated as adverse events (AE) of special interest.

Event rates were compared with what would be expected with psoriasis or the gen- �

eral population using external databases: serious infection (Marketscan database), solid tumors (SEER database), and myocardial infarction (MI)/stroke (Framingham database)

Results

Figure 1. Duration of ustekinumab exposure

≥ 6months

≥ 1year

≥ 1.5years

≥ 2years

≥ 2.5years

≥ 3years

0

500

1000

1500

2000

2500

3000

Pat

ient

s (N

)

1970

2414

1285

1852

373

1694

0

1247

0

611

0157

2007 Analyses [through Year 1.5] (N = 2266, Patient-years of follow-up = 2251)

2009 Analyses [through Year 3] (N = 3117, Patients-years of follow-up = 4782)

The 2007 analysis (through Year 1.5) included 2266 patients treated with 2251 �

patient-years (PY) of follow-up (Figure 1)

The 2009 analysis (through Year 3) included substantially more data on a total of �

3117 patients with 4782 patient-years of follow-up, with 1247 patients treated at least 2 years (Figure 1)

Demographics and baseline patient characteristics were similar across all 4 trials �

(Table 1)

Table 1. Patient baseline demographicsPhase 2 PHOENIX 1 PHOENIX 2 ACCEPT

Patients randomized, n 320 766 1230 903

Age, yrs* 44.9 (45.0) 45.3 (45.5) 46.2 (47.0) 45.2 (45.0)

Male, n (%) 222 (69.4%) 531 (69.3%) 840 (68.3%) 613 (67.9%)

Weight, kg* 93.0 (89.0) 93.9 (91.6) 91.0 (88.6) 90.8 (88.5)

Height, cm 171.8 (172.0) 172.0 (173.0) 172.2 (173.0) 172.8 (173.0)

PsO duration, years* 18.2 (16.1) 19.9 (18.3) 20.1 (18.5) 18.8 (17.2)

Age at diagnosis, yrs 26.8 (24.5) 25.4 (23.0) 26.2 (24.0) 26.4 (24.0)

BSA, % affected* 27.2 (21.0) 26.7 (21.0) 26.4 (20.0) 25.3 (20.0)

PsA, n (%) 62 (19.4%) 258 (33.7%) 306 (24.9%) 252 (27.9%)

PASI score (0-72)* 19.1 (16.4) 20.2 (17.6) 19.6 (17.5) 19.5(17.0)

PGA marked or severe, n (%) NA 335 (43.8%) 488 (39.7%) 390 (43.3%)

Prior biologic therapy, n (%) NA 392 (51.2%) 466 (37.9%) 103 (11.4%)

Prior conventional systemic therapy (≥1 therapy), n (%)

161 (50.3%) 424 (55.4%) 688 (55.9%) 533 (59.0%)

*Values are mean (median)NA: Not collected in Phase 2 study

During the common 12-week controlled period of the trials, 50.4%, 57.6%, and �

51.6% of patients treated with placebo, ustekinumab 45 mg, and ustekinumab 90 mg, respectively, experienced ≥1 AE ; 1.4%, 1.6%, and 1.4%, respectively, experienced ≥1 serious AE (SAE) (Table 2)

In these respective groups, placebo, ustekinumab 45 mg, and ustekinumab 90 mg, �

23.2%, 27.0%, and 24.1% experienced ≥1 infection, and 1.9%, 1.1%, and 1.4% experienced an AE leading to treatment discontinuation during the controlled period (Table 2)

Cumulative rates of AEs, SAEs, infections, and AEs leading to study agent discontinua- �

tion during the controlled and uncontrolled periods for up to 1.5 years did not increase disproportionally over time or with increased duration of drug exposure (Table 2)

Table 2. Adverse events for patients treated up to 1.5 years Common 12-week placebo-controlled period

(Phase 2, PHOENIX 1 & 2)1.5 Years

(Phase 2, PHOENIX 1 & 2)

PBO UST 45 mg UST 90 mg UST 45 mg UST 90 mg

Patients treated 732 790 792 1110 1156

Total years of patient follow-up 177 203 203 1113 1138

Patients with ≥1 AE 369(50.4%) 455(57.6%) 409(51.6%) 951 (85.7%) 948 (82.0%)

Patients with ≥1 SAE 10 (1.4%) 13 (1.6%) 11 (1.4%) 65 (5.9%) 54 (4.7%)

Patients with ≥1 infection 170 (23.2%) 213 (27.0%) 191 (24.1) 695 (62.6%) 694 (60.0%)

Patients with ≥1 AE leading to treatment discontinuation

14 (1.9%) 9 (1.1%) 11 (1.4%) 36 (3.2%) 33 (2.9%)

Adverse Events of Special InterestAdverse events of special interest, including serious infections and infections requir- �

ing antibiotics, malignancies, and major adverse cardiovascular events were reviewed by 3 cumulative periods: placebo controlled period (12- 20 weeks), through the con-trolled and uncontrolled periods at both 1.5 years and 3 years (Figures 2, 3, 4, 5, 6)

Overall, rates of serious infection, serious cardiovascular events, and malignancy �

adjusting for follow-up did not increase with time or duration of ustekinumab expo-sure for up to 3 years (Figures 2, 3, 4, 5, 6)

Serious Infections and Infections Requiring Antimicrobial TreatmentDuring the controlled period, serious infection rates were 1.70/100 patient-years (PY) �

for placebo compared with 0.49/100 PY and 1.97/100 PY for ustekinumab 45 and 90 mg dosing, respectively (Figure 2)

In the 1.5- and 3-year analyses, rates of serious infections and infections requiring �

antibiotics remained stable with increasing duration of exposure

Rates of serious infection observed in this trial were consistent with rates expected in the �

psoriasis population using the Marketscan Database. For the combined ustekinumab group:

Expected event rate per 100 patient-years (95% CI)= 1.51 (1.18-1.90) —

Observed event rate per 100 patient-years (95% CI)= 1.19 (0.90-1.54) —

Figure 2. Event rate of serious infections per 100 patient-years (PY)

Controlled Period

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1113 1138 2251 2184 2598 4782

# of events 3 1 4 5 12 12 24 18 39 57

2007 Analysis 2009 Analysis

Through Week 12 or 20 Through Year 1.5 Through Year 3

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)

Placebo Ustekinumab 45 mg Ustekinumab 90 mg Ustekinumab combined

1.70(0.35, 4.96)

0.49(0.01, 2.74)

1.97(0.54, 5.03)

1.23(0.40, 2.87)

1.08(0.56, 1.88) 1.05

(0.54, 1.84)

1.07(0.68, 1.59)

0.82(0.49, 1.30)

1.50(1.07, 2.05)

1.19(0.90, 1.54)

The number of treated infections and infections requiring antibiotics per 100 patient- �

years of follow-up was stable through 3 years (Figure 3)

Figure 3. Incidence of treated infections per 100 patient-years

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1113 1138 2251 2184 2598 4782


0

20

40

60

80

100

Inci

denc

e pe

r 10

0 P

Y

36.2 37.4 38.8 38.1 37.2 36.0 36.6 34.9 34.7 34.8

Controlled Period 2007 Analysis 2009 Analysis


MalignanciesDuring the controlled period, non-melanoma skin cancer (NMSC) and non-NMSC �

malignancies (all malignancies including melanoma and lymphoma) did not occur at higher rates with ustekinumab than with placebo (Figures 4, 5)

In the 1.5- and 3-year analyses, rates of both NMSC and non-NMSC malignancies �

remained low and were stable with increasing duration of exposure

Rates for non-NMSC malignancies observed in these trials over 3 years were consis- �

tent with rates expected in the general U.S. population using the SEER Database

SIR (95% CI)= 1.05 (0.69-1.53) —

Figure 4. Incidence of NMSC per 100 PY

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1111 1134 2245 2178 2591 4769

# of events 2 1 2 3 7 11 18 14 20 34

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


1.13(0.14, 4.09)

0.49(0.01, 2.75)

0.98(0.12, 3.55) 0.74

(0.15, 2.16) 0.63(0.25, 1.30)

0.97(0.48, 1.74) 0.80

(0.48, 1.27) 0.64(0.35, 1.08)

0.77(0.47, 1.19) 0.71

(0.49, 1.00)



Figure 5. Incidence of non-NMSC malignancies per 100 PY

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1111 1138 2249 2180 2594 4774

# of events 1 1 0 1 7 1 8 15 12 27

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


0.57(0.01, 3.15) 0.49

(0.01, 2.75)

0.00(0.00, 1.47)

0.25(0.01, 1.37)

0.63(0.25, 1.30)

0.09(0.00, 0.49)

0.36(0.15, 0.70)

0.69(0.39, 1.13)

0.46(0.24, 0.81)

0.57(0.37, 0.82)



Cardiovascular (CV) EventsRates of major adverse CV events, including CV death, myocardial infarction, and �

stroke, were evaluated

During the placebo-controlled period, there were no CV events in the placebo group �

compared to 5 in the combined ustekinumab-treated patients (3 events in Phase 2 and 2 events in Phase 3) for a rate of 1.23/100 PY (Figure 6)

With extended exposure at both 1.5 and 3 years, rates of major CV events were low �

and remained stable without evidence of a dose response.

Rates of MI and stroke observed in these trials were consistent with or lower than the �

rates expected in the general population using the Framingham database

SIR (95% CI)=0.52 (0.31-0.84) —

Figure 6. Incidence of major adverse cardiovascular events* per 100 PY

n 732 790 792 1582 732 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 182 1113 1138 2251 2184 2598 4782

# of events 0 2 3 5 1 6 4 10 9 9 18

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


0.00(0.00, 1.69)

0.98(0.12, 3.56)

1.47(0.30, 4.31) 1.23

(0.40, 2.87)

0.55(0.01, 3.06)

0.54(0.20, 1.17) 0.35

(0.10, 0.90)

0.44(0.21, 0.82)

0.41(0.19, 0.78) 0.35

(0.16, 0.66)

0.38(0.22, 0.59)



* Serious cardiovascular events: sudden cardiac death, serious myocardial infarction events, and serious stroke events.

Limitation

The lack of placebo control group beyond 12 weeks for the phase 3 trials and 20 weeks �

for the phase 2 trial limits the comparisons of these analyses of rare events

Conclusions

The ustekinumab psoriasis clinical safety database is large with over 3000 patients �

treated for up to 3 years

Adverse event rates remained stable through 3 years without evidence of cumulative �

toxicity.

These analyses support a favorable benefit/risk profile for ustekinumab with up to �

3 years of treatment, a profile which will continue to be elucidated in 2 ongoing Phase 3 studies.

References1. Krueger GG, et al. N Engl J Med. 2007;356:580–592.

2. Papp K, et al. Lancet. 2008;371:1675-1684.

3. Leonardi C, et al. Lancet. 2008;371:1665-1674.

This study was supported by Centocor Ortho Biotech, Inc.

The Ustekinumab Safety Experience in Patients with Moderate-to-severe Psoriasis: Results from Pooled Analyses of Phase 2 and Phase 3 Clinical Trial DataK. Gordon,1 C. Leonardi,2 N. Yeilding,3 K. Reich4

1Division of Dermatology, NorthShore University Health Systems and the University of Chicago, Evanston, IL; 2Central Dermatology, St. Louis, MO; 3Centocor Research & Development, Inc., Malvern, PA; 4Dermatologikum Hamburg, Hamburg, Germany

CLICK ON HEADINGS, SUBHEADINGS, TABLES, FIGURES, OR HYPERLINKS TO ENLARGE


fmangiol

Text Box

Depositato presso AIFA in data xx/xx/2010 - RCP, Regime di Fornitura, Classe e Prezzo in allegato


Previous Next

Background

Ustekinumab is a human, monoclonal antibody that binds to the shared p40 subunit of interleukins 12 and 23 and, therefore, inhibits binding to their receptors. In Phase 2 and Phase 3 (PHOENIX 1 and 2) psoriasis stud-ies, ustekinumab therapy has been shown to be highly efficacious in treating patients with moderate to severe psoriasis with a favorable benefit/risk profile.1,2,3



Previous Next

Objectives

To analyze the cumulative safety experience with up to 76 weeks of treatment (referred to as the 1.5-Year JJ

Safety Analysis) with ustekinumab across Phase 2 and 3 psoriasis clinical trials

To analyze selected adverse events of interest (i.e., serious infections, malignancies and cardiovascular events) JJ

in recently locked data with up to 152 weeks of treatment (referred to as the 3-Year Safety Analysis)



Previous Next

Methods

To evaluate the safety of ustekinumab in the overall psoriasis clinical development program, safety data was JJ

pooled data across psoriasis Phase 2 and Phase 3 studies on two separate occasions based on all data available at the time of the analyses (referred to as 1.5-Year Safety Analyses and 3-Year Safety Analyses).

The 1.5-Year Safety Analyses (n=2266) occurred based on all data available in database locks that occurred JJ

through October 2007, including:




The 3-Year Safety Analyses (n=3117) occurred based on all data available in database locks that occurred JJ

through May 2009, including:




64 weeks of data from the ACCEPT Phase 3 trial comparing ustekinumab and etanercept safety —and efficacy

Methods



Previous Next

Cumulative safety was evaluated during the placebo-controlled period (12- 20 weeks), with up to 1.5 years JJ

of treatment, and with up to 3 years of treatment. Serious infections and infections requiring antibiotics, malignancies, and major adverse cardiovascular events were evaluated as adverse events (AE) of special interest.

Event rates were compared with what would be expected with psoriasis or the general population using JJ

external databases: serious infection (Marketscan database), solid tumors (SEER database), and myocar-dial infarction (MI)/stroke (Framingham database)

Methods



Previous Next

Results

Figure 1. Duration of ustekinumab exposure

≥ 6months

≥ 1year

≥ 1.5years

≥ 2years

≥ 2.5years

≥ 3years

0

500

1000

1500

2000

2500

3000P

atie

nts

(N)

1970

2414

1285

1852

373

1694

0

1247

0

611

0157

2007 Analyses [through Year 1.5] (N = 2266, Patient-years of follow-up = 2251)

2009 Analyses [through Year 3] (N = 3117, Patients-years of follow-up = 4782)

The 2007 analysis (through Year 1.5) included 2266 patients treated with 2251 patient-years (PY) of JJ

follow-up (Figure 1)

The 2009 analysis (through Year 3) included substantially more data on a total of 3117 patients with 4782 JJ

patient-years of follow-up, with 1247 patients treated at least 2 years (Figure 1)

Results



Previous Next

Demographics and baseline patient characteristics were similar across all 4 trials (JJ Table 1)

Table 1. Patient baseline demographicsPhase 2 PHOENIX 1 PHOENIX 2 ACCEPT

Patients randomized, n 320 766 1230 903

Age, yrs* 44.9 (45.0) 45.3 (45.5) 46.2 (47.0) 45.2 (45.0)

Male, n (%) 222 (69.4%) 531 (69.3%) 840 (68.3%) 613 (67.9%)

Weight, kg* 93.0 (89.0) 93.9 (91.6) 91.0 (88.6) 90.8 (88.5)

Height, cm 171.8 (172.0) 172.0 (173.0) 172.2 (173.0) 172.8 (173.0)

PsO duration, years* 18.2 (16.1) 19.9 (18.3) 20.1 (18.5) 18.8 (17.2)

Age at diagnosis, yrs 26.8 (24.5) 25.4 (23.0) 26.2 (24.0) 26.4 (24.0)

BSA, % affected* 27.2 (21.0) 26.7 (21.0) 26.4 (20.0) 25.3 (20.0)

PsA, n (%) 62 (19.4%) 258 (33.7%) 306 (24.9%) 252 (27.9%)

PASI score (0-72)* 19.1 (16.4) 20.2 (17.6) 19.6 (17.5) 19.5(17.0)

PGA marked or severe, n (%) NA 335 (43.8%) 488 (39.7%) 390 (43.3%)

Prior biologic therapy, n (%) NA 392 (51.2%) 466 (37.9%) 103 (11.4%)

Prior conventional systemic therapy (≥1 therapy), n (%)

161 (50.3%) 424 (55.4%) 688 (55.9%) 533 (59.0%)

*Values are mean (median)NA: Not collected in Phase 2 study

Results



Previous Next

During the common 12-week controlled period of the trials, 50.4%, 57.6%, and 51.6% of patients treated JJ

with placebo, ustekinumab 45 mg, and ustekinumab 90 mg, respectively, experienced ≥1 AE ; 1.4%, 1.6%, and 1.4%, respectively, experienced ≥1 serious AE (SAE) (Table 2)

In these respective groups, placebo, ustekinumab 45 mg, and ustekinumab 90 mg, 23.2%, 27.0%, and JJ

24.1% experienced ≥1 infection, and 1.9%, 1.1%, and 1.4% experienced an AE leading to treatment dis-continuation during the controlled period (Table 2)

Cumulative rates of AEs, SAEs, infections, and AEs leading to study agent discontinuation during the con-JJ

trolled and uncontrolled periods for up to 1.5 years did not increase disproportionally over time or with increased duration of drug exposure (Table 2)

Table 2. Adverse events for patients treated up to 1.5 years Common 12-week placebo-controlled period

(Phase 2, PHOENIX 1 & 2)1.5 Years

(Phase 2, PHOENIX 1 & 2)

PBO UST 45 mg UST 90 mg UST 45 mg UST 90 mg

Patients treated 732 790 792 1110 1156

Total years of patient follow-up 177 203 203 1113 1138

Patients with ≥1 AE 369(50.4%) 455(57.6%) 409(51.6%) 951 (85.7%) 948 (82.0%)

Patients with ≥1 SAE 10 (1.4%) 13 (1.6%) 11 (1.4%) 65 (5.9%) 54 (4.7%)

Patients with ≥1 infection 170 (23.2%) 213 (27.0%) 191 (24.1) 695 (62.6%) 694 (60.0%)

Patients with ≥1 AE leading to treatment discontinuation

14 (1.9%) 9 (1.1%) 11 (1.4%) 36 (3.2%) 33 (2.9%)

Results



Previous Next

Adverse Events of Special InterestAdverse events of special interest, including serious infections and infections requiring antibiotics, malignan-JJ

cies, and major adverse cardiovascular events were reviewed by 3 cumulative periods: placebo controlled period (12- 20 weeks), through the controlled and uncontrolled periods at both 1.5 years and 3 years (Figures 2, 3, 4, 5, 6)

Overall, rates of serious infection, serious cardiovascular events, and malignancy adjusting for follow-up did JJ

not increase with time or duration of ustekinumab exposure for up to 3 years (Figures 2, 3, 4, 5, 6)

Serious Infections and Infections Requiring Antimicrobial TreatmentDuring the controlled period, serious infection rates were 1.70/100 patient-years (PY) for placebo compared JJ

with 0.49/100 PY and 1.97/100 PY for ustekinumab 45 and 90 mg dosing, respectively (Figure 2)

In the 1.5- and 3-year analyses, rates of serious infections and infections requiring antibiotics remained JJ

stable with increasing duration of exposure

Rates of serious infection observed in this trial were consistent with rates expected in the psoriasis popula-JJ

tion using the Marketscan Database. For the combined ustekinumab group:

Expected event rate per 100 patient-years (95% CI)= 1.51 (1.18-1.90) —

Observed event rate per 100 patient-years (95% CI)= 1.19 (0.90-1.54) —

Results



Previous Next

Figure 2. Event rate of serious infections per 100 patient-years (PY)

Controlled Period

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1113 1138 2251 2184 2598 4782

# of events 3 1 4 5 12 12 24 18 39 57

2007 Analysis 2009 Analysis


0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


1.70(0.35, 4.96)

0.49(0.01, 2.74)

1.97(0.54, 5.03)

1.23(0.40, 2.87)

1.08(0.56, 1.88) 1.05

(0.54, 1.84)

1.07(0.68, 1.59)

0.82(0.49, 1.30)

1.50(1.07, 2.05)

1.19(0.90, 1.54)

Results



Previous Next

The number of treated infections and infections requiring antibiotics per 100 patient-years of follow-up was JJ

stable through 3 years (Figure 3)

Figure 3. Incidence of treated infections per 100 patient-years

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1113 1138 2251 2184 2598 4782


0

20

40

60

80

100In

cide

nce

per

100

PY

36.2 37.4 38.8 38.1 37.2 36.0 36.6 34.9 34.7 34.8



Results



Previous Next

MalignanciesDuring the controlled period, non-melanoma skin cancer (NMSC) and non-NMSC malignancies (all malig-JJ

nancies including melanoma and lymphoma) did not occur at higher rates with ustekinumab than with pla-cebo (Figure 4, 5)

In the 1.5- and 3-year analyses, rates of both NMSC and non-NMSC malignancies remained low and were JJ

stable with increasing duration of exposure

Rates for non-NMSC malignancies observed in these trials over 3 years were consistent with rates expected JJ

in the general U.S. population using the SEER Database

SIR (95% CI)= 1.05 (0.69-1.53) —

Results



Previous Next

Figure 4. Incidence of NMSC per 100 PY

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1111 1134 2245 2178 2591 4769

# of events 2 1 2 3 7 11 18 14 20 34

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


1.13(0.14, 4.09)

0.49(0.01, 2.75)

0.98(0.12, 3.55) 0.74

(0.15, 2.16) 0.63(0.25, 1.30)

0.97(0.48, 1.74) 0.80

(0.48, 1.27) 0.64(0.35, 1.08)

0.77(0.47, 1.19) 0.71

(0.49, 1.00)



Results



Previous Next

Figure 5. Incidence of non-NMSC malignancies per 100 PY

n 732 790 792 1582 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 1111 1138 2249 2180 2594 4774

# of events 1 1 0 1 7 1 8 15 12 27

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


0.57(0.01, 3.15) 0.49

(0.01, 2.75)

0.00(0.00, 1.47)

0.25(0.01, 1.37)

0.63(0.25, 1.30)

0.09(0.00, 0.49)

0.36(0.15, 0.70)

0.69(0.39, 1.13)

0.46(0.24, 0.81)

0.57(0.37, 0.82)



Results



Previous Next

Cardiovascular (CV) EventsRates of major adverse CV events, including CV death, myocardial infarction, and stroke, were evaluatedJJ

During the placebo-controlled period, there were no CV events in the placebo group compared to 5 in JJ

the combined ustekinumab-treated patients (3 events in Phase 2 and 2 events in Phase 3) for a rate of 1.23/100 PY (Figure 6)

With extended exposure at both 1.5 and 3 years, rates of major CV events were low and remained stable JJ

without evidence of a dose response.

Rates of MI and stroke observed in these trials were consistent with or lower than the rates expected in the JJ

general population using the Framingham database

SIR (95% CI)=0.52 (0.31-0.84) —

Results



Previous Next

Figure 6. Incidence of major adverse cardiovascular events* per 100 PY

n 732 790 792 1582 732 1110 1156 2266 1319 1906 3117

Patient years 177 203 203 406 182 1113 1138 2251 2184 2598 4782

# of events 0 2 3 5 1 6 4 10 9 9 18

0.0

1.0

2.0

3.0

4.0

Inci

denc

e pe

r 10

0 P

Y (

95%

CI)


0.00(0.00, 1.69)

0.98(0.12, 3.56)

1.47(0.30, 4.31) 1.23

(0.40, 2.87)

0.55(0.01, 3.06)

0.54(0.20, 1.17) 0.35

(0.10, 0.90)

0.44(0.21, 0.82)

0.41(0.19, 0.78) 0.35

(0.16, 0.66)

0.38(0.22, 0.59)



* Serious cardiovascular events: sudden cardiac death, serious myocardial infarction events, and serious stroke events.

Results



Previous Next

Limitation

The lack of placebo control group beyond 12 weeks for the Phase 3 trials and 20 weeks for the Phase 2 JJ

trial limits the comparisons of these analyses of rare events



Previous Next

Conclusions

The ustekinumab psoriasis clinical safety database is large with over 3000 patients treated for up to JJ

3 years

Adverse event rates remained stable through 3 years without evidence of cumulative toxicity.JJ

These analyses support a favorable benefit/risk profile for ustekinumab with up to 3 years of treatment, a JJ

profile which will continue to be elucidated in 2 ongoing Phase 3 studies.



Previous Next

References

1. Krueger GG, et al. N Engl J Med. 2007;356:580–592.

2. Papp K, et al. Lancet. 2008;371:1675-1684.

3. Leonardi C, et al. Lancet. 2008;371:1665-1674.


Documents

prova