Module 1
Targeting the T cell in RA earlier
Disease: Safety Concerns
Prof. Hassan Bassiouny, MD
Prof. Of Rheumatology,
Al-Azhar University
Cairo, Egypt
RHUHQ12PM028
Date of preparation: January 2012
Module 1
Abatacept is indicated as a first-line biologic agent in
methotrexate inadequate responder (MTX-IR) patients
Abatacept demonstrates similar short-term efficacy compared with
other biologic agents
• “The data seem to indicate that abatacept has similar short-term efficacy when compared to infliximab,
etanercept and rituximab”
Abatacept demonstrates more favourable maintenance of
long-term efficacy
• “It appears that the retention rates at the end of 4 years of the LT therapy were comparable or higher
in the abatacept study (73%) compared to the 3 TNF-antagonists (56–74%)”
• “The ACR50 and DAS28 response rates were comparable or higher in the abatacept study compared
with the 3 TNF-antagonists”
Abatacept seems to have a favourable safety profile
• “According to current safety database, the safety profile of abatacept seems to be better than that of
the TNF-inhibitors and rituximab. This is due to the lower occurrence of serious or other infections”
EPAR Orencia: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_
Discussion_-_Variation/human/000701/WC500095025.pdf.
2
Module 1
ATTEST (MTX-IR)
% of patients with serious infection
Less than 2% of patients experienced serious
infections with abatacept over 1 year
9
8.5%
8
7
6
5
4
3
1.9%
2
1
0
Infliximab + MTX
(n=165)
Abatacept + MTX
(n=156)
This study was not designed to demonstrate non-inferiority or superiority of abatacept vs infliximab.
Schiff M, et al. Ann Rheum Dis 2008;67:1096–1103.
3
Module 1
ATTEST (MTX-IR)
Abatacept shows a more acceptable safety profile
than infliximab
Serious infection events, % (n)
Infliximab + MTX (n=165)
Abatacept + MTX (n=156)
8.5 (14)
1.9 (3)
1.8 (3)
1.3 (2)
Infection skin ulcer
0
0.6 (1)
Sinusitis
0
0.6 (1)
Bronchitis
0.6 (1)
0
Cellulitis
0.6 (1)
0
Encephalitis herpetic
0.6 (1)
0
Erysipelas
0.6 (1)
0
Gastroenteritis
0.6 (1)
0
Herpes zoster
0.6 (1)
0
Lung infection (pseudomonal)
0.6 (1)
0
Peritoneal tuberculosis
0.6 (1)
0
Pneumocystis jiroveci pneumonia
0.6 (1)
0
Postoperative wound infection
0.6 (1)
0
Lobar pneumonia
0.6 (1)
0
Pulmonary tuberculosis
0.6 (1)
0
Septic shock
0.6 (1)
0
Infections and infestations (total)
Pneumonia
There were
0
opportunistic
infections in patients
treated with
abatacept
Serious infection events between Day 1 and Day 365. Orange bars indicate opportunistic infections.
This study was not designed to demonstrate non-inferiority or superiority of abatacept vs infliximab.
Schiff M, et al. Ann Rheum Dis 2008;67:1096–1103.
4
Module 1
COCHRANE META-ANALYSIS
Abatacept is associated with fewer serious adverse events
and serious infections compared to other biologic agents
Forest plots: Serious adverse events and serious infections
Serious adverse events
Abatacept
Adalimumab
Anakinra
Certolizumab
Etanercept
Golimumab
Infliximab
Rituximab
Tocilizumab
Overall
P (drug)=0.099
Serious infections
Abatacept
Adalimumab
Anakinra
Certolizumab
Etanercept
Golimumab
Infliximab
Rituximab
Tocilizumab
Overall
P (drug)=0.027
0.1
1.0
Favours biologic
Odds ratio (95% CI)
Singh JA, et al. Cochrane Database Syst Rev 2011:16;2:CD008794.
10.0
Favours placebo
5
Module 1
Integrated safety summary
Incidence rates of serious infections are stable
over time across 8 abatacept clinical trials
Incidence rate (per 100 p–y)
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0
0
1
2
3
4
5
6
7
Year
Patients with
event, n
Incidence rates per
100 p–y (95% CI)
131
70
47
40
23
13
8
3.7
(3.1–4.4)
2.9
(2.2–3.6)
2.4
(1.7–3.2)
2.5
(1.8–3.4)
1.9
(1.2–2.8)
2.5
(1.3–4.2)
3.1
(1.3–6.0)
Data lock December 2009; 12,132 p–y of exposure (N=4,149) Serious infection is a subset of serious adverse events; p–y=patient–years.
Hochberg M, et al. Arthritis Rheum 2010;62(Suppl10):S164–5. Abstract 390.
6
Module 1
Integrated safety summary
Continued use of abatacept does not increase the
risk of malignancy over time
Clinical trial
experience
Short term
Short term
(2,331 p–y)
Long term
(9,752 p–y)
Cumulative
(12,132 p–y)
Placebo
Abatacept
Abatacept
Abatacept
0.59
(0.19–1.37)
0.69
(0.39–1.11)
0.74
(0.58–0.93)
0.73
(0.58–0.89)
–
0.04
(0.00–0.24)
0.08
(0.04–0.16)
0.07
(0.03–0.14)
0.59
(0.19–1.37)
0.60
(0.33–1.01)
0.60
(0.45–0.77)
0.59
(0.46–0.75)
–
0.21
(0.07–0.50)
0.13
(0.07–0.23)
0.15
(0.09–0.23)
0.82
(0.33–1.70)
0.82
(0.49–1.28)
0.74
(0.58–0.93)
0.73
(0.58–0.90)
Malignancies, incidence rate (95% CI)
Malignancies
(excluding NMSC)
Lymphoma
Total solid organ
(combined)
Lung cancer
NMSC
NMSC=non-melanoma skin cancer; Data over a 7-year period; Data lock December 2009. 12,132 p–y of exposure (N=4,149).
Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–5. Abstract 390.
7
Module 1
Integrated safety summary
Standardised incidence ratios of malignancies for abatacept
patients are comparable with the general population
Total
(excluding non-melanoma skin)
Breast
Colon and rectal
Lung
Lymphoma
0.01
0.1
1
10
100
Orange lines indicate the standard incidence ratio point estimates and the 95% confidence intervals for abatacept (2006 ISS database lock)
compared with the SEER database of the general population; The diamonds represent SIR reported in the literature that compare RA patients with
non-RA patients or general populations; SEER=Surveillance, Epidemiology and End Results.
Simon TA, et al. Ann Rheum Dis 2009;68:1819–1826.
8
Module 1
Integrated safety summary
Standardised incidence ratios of lung cancer for abatacept
patients are not increased compared with non-biologic
DMARD-treated RA population
Abatacept RCT vs
BC
NDB
GPRD
NOAR
Sweden ERA
0.1
1
Standardised incidence rations
10
The diamonds indicate the standard incidence ratio point estimates and the horizontal line represent the 95% confidence intervals for abatacept
(2006 ISS database lock) compared with the RA population treated with non-biologic DMARDs in cohorts.
Simon TA, et al. Ann Rheum Dis 2009;68:1819–1826.
9
Module 1
Integrated safety summary
Standardised incidence ratios of lymphoma for abatacept
patients are not increased compared with non-biologic
DMARD-treated RA population
Abatacept RCT vs
BC
NDB
GPRD
NOAR
Sweden ERA
0.1
1
Standardised incidence rations
10
The diamonds indicate the standard incidence ratio point estimates and the horizontal line represent the 95% confidence intervals for abatacept
(2006 ISS database lock) compared with the RA population treated with non-biologic DMARDs in cohorts.
Simon TA, et al. Ann Rheum Dis 2009;68:1819–1826.
10
Module 1
REAL-LIFE DATA
Summary of safety experience with abatacept in RABBIT
and ORA registries in anti-TNF-IR patients
RABBIT1
ORA2
n=261; 420 p–y
1187.7 p–y exposure
30 April 2011
December 2010
Infections
Abatacept patients
Cut-off date
Serious infections
4.8/100 p–y
Total malignancies
0.78/100 p–y†
Deaths
n=5
1.19/100 p–y
n=66
5.6/100 p–y
n=14
1.18/100 p–y
n=16
Anaphylactic reactions
0.48/100 p–y
Not reported
Severe infusion reactions leading
to discontinuations
Not reported
n=9
•
No opportunistic infection reported in RABBIT or ORA
†Number
of solid malignancies (ITT population; 516 patient–years).
1. Strangfeld A, personal communication; 2. Gottenberg JE, Ann Rheum Dis 2011;70(Suppl3):466.
11
Module 1
LT- RCT
Abatacept has a retention rate that is comparable
with or higher than the anti-TNF agents
Subjects remaining at the end of 4 years of LTE
n/N
%
Infliximab1
295/511
62%
Etanercept2
429/581
74%
Adalimumab3
147/262
56%
394/539
73%
Abatacept4*
(IM101102)
•
Retention may be considered as a surrogate marker of long-term
efficacy for biologic agents5
*Summation of the original abatacept plus placebo treatment groups who entered LTE.
Data from literature search on the long-term efficacy results from open-label extension studies of anti-TNFs (in MTX-naïve and MTX-IR patients).
1. Vander Cruyssen B, et al. Arthritis Res Ther 2006;8:R112; 2. Moreland LW, et al. J Rheum 2006;33:854–861;
3. Weinblatt M, et al. Ann Rheum Dis 2006;65:753–759; 4. Data on file; 5. Hetland ML, et al. Arthitis Rheum 2010;62:22–32.
12
Module 1
Abatacept seems to have a favourable safety profile:
Summary
Rates of serious infections lower with
abatacept vs other biologic agents1–3
No increases in incidence rates of malignancy3
with abatacept over time
Retention rates seen in real-life study were
consistent with clinical trial data4
1. Schiff M, et al. Ann Rheum Dis 2008;67:1096–1103; 2. Singh JA, et al. Cochrane Database Syst Rev.
2011:16;2:CD008794; 3. Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–165. Abstract 390;
4. Schiff M, et al. Int J Clin Rheum 2010;5:581–591.
13
Module 1
Abatacept…
Has demonstrated similar short-term efficacy
compared with other biologic agents1
…has demonstrated more favourable
maintenance of long-term efficacy...2
…seems to have a
favourable safety profile3
1. Singh JA, et al. Cochrane Database Syst Rev 2009;4:CD007848; 2. Westhovens R, et al. Ann Rheum Dis
2009;68(Suppl3):577. Poster SAT0108; 3. Singh JA, et al. Cochrane Database Syst Rev. 2011:16;2:CD008794.
14
Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
15
Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
16
Module 1
Integrated safety summary
Abatacept integrated safety analysis:
Population
• Long-term safety using an integrated analysis of data from
across 8 abatacept RA clinical trial programmes
– All patients who received ≥1 dose of study drug were evaluated
• Cumulative period included 4,149 patients treated with
abatacept with 12,132 patient-years of exposure
– 1,165 (28.1%) had ≥5 years of exposure
– Mean (SD) duration of exposure was 35.6 (26.2) months
Hochberg M, et al. Arthritis Rheum 2010;62(Suppl10):S164–5. Abstract 390.
17
Module 1
Integrated safety summary
Abatacept integrated safety analysis: multiple
large-scale trials of varying RA patient populations
PATIENT
STUDY
Short-term
period
Long-term
period
Etanercept
-IR
MTX-IR
DMARDs
and/or
biologic-IR
Anti-TNF-IR
Phase II
study
AIM
ATTEST
Phase II
ABA+ETA
ASSURE
ATTAIN
ARRIVE
Phase II
MoA study
n=3391
n=6523
n=4316
n=1212
n=1,4415
n=3914
n=1,0467
n=168
6-mth
DB, PC
6-mth
OL
12-mth
DB, PC
OL, long-term extension period* (includes patients who switched from placebo
or active-comparator arms to abatacept after the DB, PC periods)
*Generally ended when abatacept became commercially available to the patient.
1. Kremer JM, et al. Arthritis Rheum 2005;52:2263–2271; 2. Weinblatt M, et al. Ann Rheum Dis 2007;66:228–234; 3. Kremer JM, et
al. Ann Intern Med 2006;144:865–876; 4.Genovese MC, et al. N Engl J Med 2005;353:1114–1123; 5. Weinblatt M, et al. Arthritis
Rheum 2006;54:2807–2816; 6. Schiff M, et al. Ann Rheum Dis 2008;67:1096–1103; 7. Schiff M, et al. Ann Rheum Dis
2009;68:1708–1714; 8. Buch MH, et al. Ann Rheum Dis 2009;68:1220–1227.
18
Module 1
Integrated safety summary
Differences in observed AEs in abatacept in clinical
trial experience depending on treatment background
Incidence rate,
event/100 p–y
(95%CI)
MTX-naïve
N=483 (717 p–y)
MTX-IR
N=1,280 (4,465 p–y)
Anti-TNF-IR
N=1,419 (1,986 p–y)
184.37 (166.78–203.30)
260.28 (246.00–275.17)
359.05 (339.18–179.78)
Overall SAEs
6.54 (4.77–8.76)
14.62 (13.37–15.97)
20.52 (18.33–22.90)
Serious Infections
1.83 (0.97–3.12)
2.78 (2.28–3.30)
3.90 (3.06–4.89)
Malignancies
0.28 (0.03–1.01)
1.30 (0.98–1.68)
1.79 (1.25–2.49)
Overall AEs
Data from 7 clinical trials (December 2008 database lock).
Smitten A, et al. Ann Rheum Dis 2010;69(Suppl3):541. Poster SAT0164.
19
Module 1
Integrated safety summary
Deaths and serious adverse events are stable over
time in the abatacept clinical trial experience
Short-term
(n=3,173)
2,331 p–y
Long-term
(n=3,256)
9,752 p–y
Cumulative
(n=4,149)
12,132 p–y
18.15 (16.41–20.02)
14.31 (13.47–15.18)
14.61 (13.85–15.41)
Deaths
0.51 (0.27–0.90)
0.62 (0.47–0.79)
0.60 (0.47–0.76)
AEs leading to
discontinuation
6.93 (5.90–8.09)
2.79 (2.47–3.14)
3.53 (3.20–3.88)
Incidence rate
(/100 p–y)
Overall SAEs
Data from 8 clinical trials (December 2009 database lock); p–y=person-years; AE=adverse event; SAE=serious adverse event
Hochberg M, et al. Arthritis Rheum 2010;62(Suppl10):S164–5. Abstract 390.
20
Module 1
Integrated safety summary
Continued use of abatacept does not increase risk
of serious infection over time
Short term
Clinical trial experience
Long term
(n=3,256)
Cumulative
(n=4,149)
Placebo
(n=1099)
Abatacept
(n=3,173)
22
85
260
332
2.60
(1.63–3.94)
3.68
(2.94–4.55)
2.79
(2.46–3.15)
2.87
(2.57–3.19)
20
77
241
307
2.36
(1.44–3.65)
3.33
(2.63–4.16)
2.58
(2.26–2.93)
2.64
(2.35–2.95)
Infections
Serious
infections
Patients with
event, n
Incidence rate
Hospitalised
infection
Patients with
event, n
Incidence rate
2009 Database Lock
Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–5. Abstract 390.
Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
22
Module 1
ATTEST (MTX-IR)
Safety events were low in abatacept-treated
patients over 2 years
Double-blind period
Abatacept arm
(1 year; n=156)
Incidence/
100 patient-years
Double-blind period
Infliximab arm
(1 year; n=165)
Incidence/
100 patient-years
Cumulative period
All abatacept-treated
patients
(2 years; n=399)
Incidence/
100 patient-years
Adverse events
326.0 (274.1–384.9)
448.6 (380.6–525.3)
257.5 (231.8–285.3)
Serious adverse
events
11.8 (6.9–18.9)
21.1 (14.2–30.1)
15.2 (12.0–19.0)
Infections
99.8 (80.4–122.4)
134.1 (110.6–161.1)
86.2 (76.2–97.3)
Serious
infections
2.0 (0.4–5.9)
9.2 (5.0–15.5)
1.6 (0.7–3.1)
Safety event
(95% CI)
The cumulative period consists of data from patients who were 1) randomised to abatacept; 2) randomised to placebo and switched to abatacept
at Month 6; and 3) randomised to infliximab and switched to abatacept at Year 1.
Schiff M, et al. Ann Rheum Dis 2011;70:2003–2007.
23
Module 1
ATTEST (MTX-IR)
Rates of infections with abatacept are comparable with rates
for placebo- and infliximab-treated patients
Days 1–197
Days 1–365
% (n)
Abatacept
+ MTX
(n=156)
Placebo
+ MTX
(n=110)
Infliximab
+ MTX
(n=165)
Abatacept
+ MTX
(n=156)
Infliximab
+ MTX
(n=165)
Infections
48.1 (75)
51.8 (57)
52.1 (86)
59.6 (93)
68.5 (113)
Serious
infections
1.3 (2)
2.7 (3)
4.2 (7)
1.9 (3)
8.5 (14)
Schiff M, et al. Ann Rheum Dis 2008;67:1096–1103.
24
Module 1
Integrated safety summary
Continued use of abatacept does not increase risk
of serious infection over time
Short term
Clinical trial experience
Long term
(n=3,256)
Cumulative
(n=4,149)
Placebo
(n=1099)
Abatacept
(n=3,173)
22
85
260
332
2.60
(1.63–3.94)
3.68
(2.94–4.55)
2.79
(2.46–3.15)
2.87
(2.57–3.19)
20
77
241
307
2.36
(1.44–3.65)
3.33
(2.63–4.16)
2.58
(2.26–2.93)
2.64
(2.35–2.95)
Infections
Serious
infections
Patients with
event, n
Incidence rate
Hospitalised
infection
Patients with
event, n
Incidence rate
2009 Database Lock.
Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–165. Abstract 390.
Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
26
Module 1
Tuberculosis screening in abatacept clinical trials
PPD testing
PPD negative
Chest X-ray negative
PPD positive
Chest X-ray negative
PPD positive/negative
Positive chest X-ray
Diagnosis of latent TB
Prior treatment
documented
RANDOMISE
Prior treatment
not documented
DO NOT RANDOMISE
PPD=purified protein derivative; TB=tuberculosis.
Data on file
27
Module 1
Tuberculosis exclusion criteria in abatacept
clinical studies
• In the pivotal Phase II1,2 and III studies (AIM, ATTAIN and ASSURE)3–5
– Patients with a history of active TB in the 3 years before study
commencement were excluded
• In the pivotal Phase III studies (AIM, ATTAIN and ASSURE)3–5
– Patients with evidence of possible latent TB (skin testing) who had not
received adequate chemoprophylaxis were excluded
• In the ARRIVE6 study
– PPD-positive (skin testing) patients were excluded if they had positive chest
X-rays and had not received adequate chemoprophylaxis
• In total, 26 PPD-positive patients with latent TB and negative chest X-rays were
enrolled in the study
• No cases of TB were observed
PPD=purified protein derivative.
1. Kremer JM, et al. Arthritis Rheum 2005;52:2263–2271; 2. Weinblatt M, et al. Ann Rheum Dis. 2007;66:228–234;
3. Kremer JM, et al. Ann Intern Med 2006;144:865–877; 4. Genovese MC, et al. N Engl J Med 2005;144:1114–1123;
5. Weinblatt M, et al. Arthritis Rheum 2006;54:2807–2816; 6. Schiff M, et al. Ann Rheum Dis 2009;68:1708–1714.
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Module 1
Tuberculosis: Clinical trial experience
• 6 cases of suspected TB with abatacept
– Double-blind
• TB cervical lymphadenitis infection
– Open-label (OL)
• 2 pulmonary TB
• 1 Pott’s disease (thoracic); presented with transient fever,
non-productive cough followed by a persistent thoracic pain
• 1 submandibular lymphadenitis; presented with enlarged lymph node
• 1 latent TB
• 1 case of confirmed pulmonary TB with abatacept (OL)
• 1 case of presumed tuberculosis with placebo
– Double-blind
• Suspected TB, unknown presentation
December 2008 database lock.
Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–5. Abstract 390; Data on file.
29
Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
30
Module 1
Integrated safety summary
Incidence rates of total malignancies (excluding
NMSC) in the abatacept clinical trial experience
Incidence rate (per 100 p–y)
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
0
Patients with
event, n
Incidence rates per
100 p–y (95% CI)
3
5
1
2
22
14
17
14
13
3
5
0.6
(0.4–0.9)
0.6
(0.3–0.9)
0.8
(0.5–1.3)
0.8
(0.4–1.4)
1.0
(0.5–1.7)
0.5
(0.1–1.5)
1.7
(0.5–3.9)
Year
4
6
7
NMSC=non-melanoma skin cancer; Data lock December 200912,132 p–y of exposure (n=4,149)
Hochberg M, et al. Arthritis Rheum 2010;62(Suppl10):S164–5. Abstract 390.
31
Module 1
Incidence rates of malignancies are stable over
time in the abatacept clinical trial experience
Number of events/100 p–y
Total malignancies
Non-melanoma skin
Solid
Lung
Thyroid
Breast
Prostate
Bladder
Renal
Ovarian
Melanoma
Endometrial/uterine
Cervix
Haematologic
Lymphoma
Myelodysplastic syndrome
DB period
n=1,955 (1,687 p–y)
1.61
0.95
0.53
0.24
0.12
0.06
0.06
0.06
0.06
0
0
0
0
0.12
0.06
0.06
Cumulative period
n=4,149 (11,658 p–y)
1.43
0.72
0.59
0.17
0.02
0.10
0.05
0.03
0.01
0.02
0.03
0.03
0.03
0.13
0.06
0.04
December 2008 database lock.
1. Smitten A, et al. Arthritis Rheum 2008;59(Suppl9):S786. Poster 1675(397);
2. Data on file; 3. Orencia SmPC November 2011.
32
Module 1
Malignancy: Summary
• In the cumulative abatacept experience (4,149 patients; 12,132 p–y):1,2
– Incidence of malignancy was 1.44 per 100 p–y
– Annualized incidence rate remained stable
• Incidence of malignancies with abatacept were similar to placebo and
the RA population3
– Increasing duration of exposure to abatacept did not increase the risk of
overall malignancy or major type/individual malignancy1,4
• A risk management plan will provide further information to better define
risk of malignancy
1. Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–165. Abstract 390. 2. Data on file; 3. Simon TA, et al. Ann Rheum
Dis 2009;68:1819–1826; 4. Smitten A, et al. Ann Rheum Dis 2010;69(Suppl3):541. Poster SAT0163.
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Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
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Module 1
Integrated safety summary
Incidence rates of autoimmune events are stable
over time across 8 abatacept clinical trials
Number
IR, events/100 p–y
(95%CI)
Total autoimmune AE1
•
Short-term
period*
(2,331 p–y)
Open-label
period†
(9,752 p–y)
Cumulative
periods‡
(12,132 p–y)
n=48
2.07 (1.53–2.75)
n=183
1.95 (1.68–2.25)
n=232
1.99 (1.74–2.26)
The most common autoimmune events in the cumulative period were:
• Psoriasis (IR [95% CI]: 0.57 [0.44–0.72])
• Sjogren’s syndrome (0.19 [0.12–0.29])
• Vasculitis (0.18 [0.11–0.28])
*Abatacept-treated patients; †All patients received abatacept during the open-label periods; ‡Abatacept-treated patients in the cumulative
(short-term and open-label) study periods. Data are for 8 abatacept clinical trials (short-term and open-label periods).
December 2009 database lock.
Hochberg M, et al. Arthritis Rheum 2010;62(Suppl10):S164–165. Abstract 390.
35
Module 1
Supporting safety data
•
•
•
•
•
•
Summary of safety
Infections
Tuberculosis
Malignancies
Autoimmune events
Infusion events
36
Module 1
Integrated safety summary
Incidence rates of acute infusion events reported
in abatacept-treated patients decline over time
4149 pts; 12,132 p–y
Acute
infusional events†
Patients with event, n
Incidence rate
Short term
Long term
(n=3256)
Cumulative
(n=4149)
Placebo
(n=1099)
Abatacept
(n=3173)
68
225
176
377
9.84
(7.64–12.48)
11.61
(10.14–13.22)
2.18
(1.87–2.53)
3.9
(3.52–4.32)
Database lock: December 2009.
Events occurring within one hour of the start of the infusion, evaluated in only 6 studies:
• Short-term period, n=2868 [1939 p–y] for abatacept and n=944 [691 p–y] for placebo
• Long-term period, n=2957 [8067 p–y]
• Cumulative period, n=3755 [9662 p–y]
Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S142. Abstract 390.
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Module 1
Immunogenicity was low in the abatacept clinical
trial program
• Overall incidence of anti-abatacept antibody responses was
4.8% (187/3,985) in patients treated for up to 8 years with
abatacept1
– In patients assessed for antibodies at least 42 days after
discontinuation of abatacept, incidence of immunogenicity was 5.5%
(103/1,888)1
– There was no apparent correlation of antibody development to clinical
response or adverse event based on this limited dataset of patients
with antibodies1
1. Orencia SmPC November 2011.
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Thank You