ACR 20 Response by Geographic Region at 6 Months Patients with Inadequate Response to Methotrexate
13
56 76 69 46 22 47 37 54 0 10 20 30 40 50 60 70 80 90 N orth A m erica South A m erica Europe R estofW orld % R esponders Abatacept P lacebo ACR 20 Response by Geographic Region at 6 ACR 20 Response by Geographic Region at 6 Months Months Patients with Inadequate Response to Methotrexate Patients with Inadequate Response to Methotrexate IM101-102 N = 84 41 173 93 143 67 24 13 43b - 20
description
ACR 20 Response by Geographic Region at 6 Months Patients with Inadequate Response to Methotrexate. N = 844117393143672413. 43b - 20. IM101-102. ACR 20 Response by Geographic Region at 6 Months Patients with Inadequate Response to Anti-TNF Therapy. N = 18799. 6934. 44b - 19. - PowerPoint PPT Presentation
Transcript of ACR 20 Response by Geographic Region at 6 Months Patients with Inadequate Response to Methotrexate
56
7669
46
22
47
37
54
0
10
20
30
40
50
60
70
80
90
North America South America Europe Rest of World
% R
es
po
nd
ers
Abatacept Placebo
ACR 20 Response by Geographic Region at 6 MonthsACR 20 Response by Geographic Region at 6 MonthsPatients with Inadequate Response to MethotrexatePatients with Inadequate Response to Methotrexate
IM101-102
N = 84 41 173 93 143 67 24 13
43b - 20
51 49
19 21
0
20
40
60
80
North America Europe
% R
es
po
nd
ers
Abatacept Placebo
ACR 20 Response by Geographic Region at 6 MonthsACR 20 Response by Geographic Region at 6 MonthsPatients with Inadequate Response to Anti-TNF TherapyPatients with Inadequate Response to Anti-TNF Therapy
IM101-029
N = 187 99 69 34
44b - 19
Overview of Adverse Events by AgeOverview of Adverse Events by AgeDouble-Blind, Controlled Study PeriodsDouble-Blind, Controlled Study Periods
1447 (88.7)1447 (88.7)
188 (11.5)188 (11.5)
40 (2.5)40 (2.5)9 (0.6)9 (0.6)
78 (4.8)78 (4.8)
6 (0.4) 6 (0.4)
710 (84.4)710 (84.4)
98 (11.7)98 (11.7)
15 (1.8)15 (1.8)7 (0.8)7 (0.8)
29 (3.4)29 (3.4)
5 (0.6)5 (0.6)
289 (89.5)289 (89.5)
78 (24.1)78 (24.1)
18 (5.6)18 (5.6)17 (5.3)17 (5.3)
29 (9.0) 29 (9.0)
4 (1.2) 4 (1.2)
130 (87.8)130 (87.8)
24 (16.2)24 (16.2)
4 (2.7)4 (2.7)4 (2.7)4 (2.7)
10 (6.8)10 (6.8)
1 (0.7)1 (0.7)
AEsAEs
SAEsSAEs
Serious InfectionsSerious Infections Malignancies Malignancies
Discontinuation Discontinuation due to AE due to AE
DeathDeath
< 65 years< 65 years
AbataceptAbataceptN = 1632N = 1632
PlaceboPlaceboN = 841N = 841
Number (%) of PatientsNumber (%) of Patients
65 years65 years
AbataceptAbataceptN = 323N = 323
PlaceboPlaceboN = 148N = 148
BLA/4M 65b - 3
6962
31
41
0
20
40
60
80
100
ACR 20 Response at 6 Months by AgeACR 20 Response at 6 Months by AgeDouble-Blind, Controlled Study PeriodsDouble-Blind, Controlled Study Periods
PatientsPatients< 65 years< 65 years
PatientsPatients 65 years 65 years
359 188 65 26
IM101-102 and IM101-029
Methotrexate Inadequate Methotrexate Inadequate RespondersResponders
4955
10
21
0
20
40
60
80
100
PatientsPatients< 65 years< 65 years
PatientsPatients 65 years 65 years
205 113 51 20
Abatacept
Placebo
Abatacept
Placebo
N = N =
Pe
rcen
t R
esp
on
der
sP
erc
ent
Res
po
nd
ers
Pe
rcen
t R
esp
on
der
sP
erc
ent
Res
po
nd
ers
Anti-TNF Inadequate Anti-TNF Inadequate RespondersResponders
65b - 2
Varicella – Cases of Special InterestVaricella – Cases of Special Interest Double-Blind and Open-Label CasesDouble-Blind and Open-Label Cases
Double-Blind (Non-Serious)Double-Blind (Non-Serious)
PatientPatientAge/Race/GenderAge/Race/Gender
PreferredPreferredTermTerm
(Intensity)(Intensity)OnsetOnsetDayDay
PreviousPreviousHistoryHistory
ConcurrentConcurrentSteroidSteroidDoseDose TreatmentTreatment
DurationDuration(Days)(Days)
IM101-102-80-1IM101-102-80-160/W/F60/W/F
Varicella Varicella (Possibly (Possibly Recurrent)Recurrent)(Moderate)(Moderate)
117117 YesYes PrednisonePrednisone5mg5mg ErythromycinErythromycin 1010
IM101-031-119-15IM101-031-119-1561/W/F61/W/F
VaricellaVaricella(Moderate)(Moderate) 297297 YesYes PrednisolonePrednisolone
10mg10mgNoneNone
ReportedReported 1717
IM101-031-202-15IM101-031-202-1548/W/F48/W/F
VaricellaVaricella(Moderate)(Moderate) 317317 NoNo NoneNone
ReportedReported AcyclovirAcyclovir 1919
All Cases resolved appropriately per investigator
62c - 6
Measures to Evaluate Effects of Abatacept Measures to Evaluate Effects of Abatacept on the Developing Immune Systemon the Developing Immune System
10 pups/gender/time point10 pups/gender/time point
Postnatal Postnatal Week 3Week 3
Postnatal Postnatal Week 7Week 7
Postnatal Postnatal Week 8Week 8
Postnatal Postnatal Week 16Week 16
Abatacept levelsAbatacept levels XX XX XX
Anti-abatacept antibodiesAnti-abatacept antibodies XX XX XX
Serum immunogulin levelsSerum immunogulin levels XX XX
Lymphoid organ weightsLymphoid organ weights XX XX
T-dependent antibody T-dependent antibody responseresponse XX
Lymphocyte and NK cell Lymphocyte and NK cell phenotypesphenotypes XX
Anti-nuclear antibodiesAnti-nuclear antibodies XX
Clinical pathologyClinical pathology XX
Histopathology – lymphoid Histopathology – lymphoid organs and organs prone to organs and organs prone to autoimmunityautoimmunity
XX
30b - 2
Effects on Developing Immune SystemEffects on Developing Immune System3-Fold Clinical Exposure3-Fold Clinical Exposure
10 pups/gender/time point10 pups/gender/time point
Postnatal Postnatal Week 3Week 3
Postnatal Postnatal Week 7Week 7
Postnatal Postnatal Week 8Week 8
Postnatal Postnatal Week 16Week 16
Abatacept levelsAbatacept levels No effectNo effect No effectNo effect No effectNo effect
Anti-abatacept antibodiesAnti-abatacept antibodies No effectNo effect No effectNo effect No effectNo effect
Serum immunogulin levelsSerum immunogulin levels No effectNo effect No effectNo effect
Lymphoid organ weightsLymphoid organ weights No effectNo effect No effectNo effect
T-dependent antibody T-dependent antibody responseresponse No effectNo effect
Lymphocyte and NK cell Lymphocyte and NK cell phenotypesphenotypes No effectNo effect
Anti-nuclear antibodiesAnti-nuclear antibodies No effectNo effect
Clinical pathologyClinical pathology No effectNo effect
Histopathology – lymphoid Histopathology – lymphoid organs and organs prone to organs and organs prone to autoimmunityautoimmunity
No effectNo effect
30b - 3
10 pups/gender/time point10 pups/gender/time point
Postnatal Postnatal Week 3Week 3
Postnatal Postnatal Week 7Week 7
Postnatal Postnatal Week 8Week 8
Postnatal Postnatal Week 16Week 16
Abatacept levelsAbatacept levels No effectNo effect No effectNo effect No effectNo effect
Anti-abatacept antibodiesAnti-abatacept antibodies No effectNo effect No effectNo effect No effectNo effect
Serum immunogulin levelsSerum immunogulin levels No effectNo effect No effectNo effect
Lymphoid organ weightsLymphoid organ weights No effectNo effect No effectNo effect
T-dependent antibody T-dependent antibody responseresponse
♀♀ 9-fold9-foldIncreaseIncrease
Lymphocyte and NK cell Lymphocyte and NK cell phenotypesphenotypes No effectNo effect
Anti-nuclear antibodiesAnti-nuclear antibodies No effectNo effect
Clinical pathologyClinical pathology No effectNo effect
Histopathology – lymphoid Histopathology – lymphoid organs and organs prone to organs and organs prone to autoimmunityautoimmunity
ThyroiditisThyroiditis
1/10 1/10 ♀♀
Effects on Developing Immune SystemEffects on Developing Immune System11-fold Clinical Exposure11-fold Clinical Exposure
30b - 4
Anti-Nuclear and ds-DNA AntibodiesAnti-Nuclear and ds-DNA AntibodiesSeroconversion by 6-Month IntervalsSeroconversion by 6-Month Intervals
Population: Double-blind, Phase III studies
Number (%) of PatientsNumber (%) of Patients
Anti-nuclear Antibody (ANA)Anti-nuclear Antibody (ANA) AbataceptAbatacept PlaceboPlacebo
6 Months6 Months Baseline Negative Baseline Negative SeroconvertedSeroconverted
N = 1137N = 1137
47 (4.1)47 (4.1)
N = 575N = 575
36 (6.3)36 (6.3)
12 Months12 Months Baseline Negative Baseline Negative SeroconvertedSeroconverted
N = 962N = 962
93 (9.7)93 (9.7)
N = 443N = 443
48 (10.8)48 (10.8)
Anti-dsDNA AntibodyAnti-dsDNA Antibody
6 Months6 Months Baseline Negative Baseline Negative SeroconvertedSeroconverted
N = 1272N = 1272
14 (1.1)14 (1.1)
N = 629N = 629
15 (2.4)15 (2.4)
12 Months12 Months Baseline Negative Baseline Negative SeroconvertedSeroconverted
N = 1062N = 1062
29 (2.7)29 (2.7)
N = 490N = 490
23 (4.7)23 (4.7)
BLA 64a - 5
Antibody Response to VaccinationAntibody Response to VaccinationStudy DesignStudy Design
Single Dose Study: open-label, randomized, parallel-groups Single Dose Study: open-label, randomized, parallel-groups 4 treatment groups (20 healthy volunteers per group):4 treatment groups (20 healthy volunteers per group):
Antibody levels evaluated at:Antibody levels evaluated at:
– BaselineBaseline
– 14 days post-vaccination14 days post-vaccination
– 28 days post-vaccination28 days post-vaccination
Visit DayVisit Day
Treatment Treatment GroupGroup
11 1414 5656
11 VV —— ——
22 VV AA ——
33 AA VV ——
44 AA —— VVA = Abatacept 750 mgA = Abatacept 750 mgV = VaccineV = Vaccine
IM101-049 24 - 3
EULAR Disease Activity Outcomes (DAS 28 – ESR)EULAR Disease Activity Outcomes (DAS 28 – ESR)Patients with Inadequate Response to MethotrexatePatients with Inadequate Response to Methotrexate
22
9.6
0.63.9
0
10
20
30
40
Low DiseaseActivity
Remission
% R
es
po
nd
ers
Abatacept (N = 366)
Placebo (N = 179)
IM101-102
28
17
2.23.8
0
10
20
30
40
Low DiseaseActivity
Remission
% R
es
po
nd
ers
Abatacept (N = 375)
Placebo (N = 183)
6 Months6 Months 1 Year1 Year
** p <0.001LOCF Analysis
Low Disease Activity: ≤ 3.2
Remission: < 2.6
**
**
**
**
43b - 49
0
10
20
30
40
50
Abatacept Placebo
pg
/mL
Mean Values of Biomarkers at 6 MonthsMean Values of Biomarkers at 6 MonthsPatients with Inadequate Response to Anti-TNF TherapyPatients with Inadequate Response to Anti-TNF Therapy
IM101-029
TNF-α
0
10
20
30
40
50
Abatacept Placebo
pg
/mL
IL-6
MMP-3
Rheumatoid Factor
Pro-inflammatory Cytokines Proteolytic Enzyme
Autoantibody
0
20
40
60
80
100
Abatacept Placebo
ng
/mL
0
50
100
150
200
250
300
Abatacept Placebo
U/m
L
Abatacept Placebo
B/L 6 Mo B/L 6 Mo
B/L 6 Mo B/L 6 Mo
B/L 6 Mo B/L 6 Mo
B/L 6 Mo B/L 6 Mo
Normal Range Normal
Range
Normal RangeNormal
Range
B/L = baseline value
p = 0.019
p < 0.001
p < 0.001
p = 0.014
44b - 67
IM101-102
-2 -1 0 1 2 3 4 5 6
AbataceptBetter
PlaceboBetter
Abatacept (N) Placebo (N)
All Patients 391 195Duration of RA at Baseline
2 years 91 35> 2 to 5 years 83 42> 5 to 10 years 99 51> 10 years 118 67
RF at Baseline
Positive 321 157Negative 46 25
CRP at Baseline (mg/dL)
1.2 100 591.2 – 2.2 94 482.2 – 4.0 92 47> 4.0 105 41
Swollen Joints
9-15 117 4916-20 97 5221-27 92 4628-56 85 48
ACR 20 at Day 169
Responders 268 79Non-responders 102 87
Treatment Difference with 95% CI
Mean Changes in Total Radiographic Scores at 1 YearMean Changes in Total Radiographic Scores at 1 YearSubgroup AnalysisSubgroup Analysis
Patients with Inadequate Response to MethotrexatePatients with Inadequate Response to Methotrexate
43b - 76
