# Presentation: 686930

## ACR 20 Response by Geographic Region at 6 MonthsPatients with Inadequate Response to Methotrexate

**ACR 20 Response by Geographic Region at 6 Months****Patients with Inadequate Response to Methotrexate**

- IM101-102

**N = ****	****84****	****41****	****173****	****93****	****143****	****67****	****24****	****13**

- 43b - 20

## ACR 20 Response by Geographic Region at 6 MonthsPatients with Inadequate Response to Anti-TNF Therapy

**ACR 20 Response by Geographic Region at 6 Months****Patients with Inadequate Response to Anti-TNF Therapy**

- IM101-029

**    ****N = ****	****187****	****99**

**69****	****34**

- 44b - 19

## Overview of Adverse Events by AgeDouble-Blind, Controlled Study Periods

**1447  (88.7)**
**  ****188  (11.5)**
**40    (2.5)****9    (0.6)**
**78    (4.8)**
**6    (0.4)  **

**710  (84.4)**
**98  (11.7)**
**15    (1.8)****7    (0.8)**
**29    (3.4)**
**5    (0.6)**

**289  (89.5)**
**  ****78  (24.1)**
**18    (5.6)****17    (5.3)**
**29    (9.0) **
**4    (1.2)  **

**130  (87.8)**
**24  (16.2)**
**4    (2.7)****4    (2.7)**
**10    (6.8)**
**1    (0.7)**

**AEs**
**SAEs**
**   ****Serious Infections****   Malignancies**
**Discontinuation ****  due to AE**
**Death**

**< 65 years**

**Abatacept**
**N = 1632**

**Placebo****N = 841**

**Number (%) of Patients**

****** ****65 years**

**Abatacept**
**N = 323**

**Placebo****N = 148**

- BLA/4M

- 65b - 3

## ACR 20 Response at 6 Months by AgeDouble-Blind, Controlled Study Periods

**ACR 20 Response at 6 Months by Age****Double-Blind, Controlled Study Periods**

**Patients****< 65 years**

**Patients******** 65 years**

**359**

**188**

**65**

**26**

- IM101-102 and IM101-029

**Methotrexate Inadequate Responders**

**Patients****< 65 years**

**Patients******** 65 years**

**205**

**113**

**51**

**20**

**N =**

**N =**

**Percent Responders**

**Percent Responders**

**Anti-TNF Inadequate Responders**

- 65b - 2

## Varicella – Cases of Special Interest Double-Blind and Open-Label Cases

| Double-Blind (Non-Serious) |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- |
| PatientAge/Race/Gender | PreferredTerm(Intensity) | OnsetDay | PreviousHistory | ConcurrentSteroidDose | Treatment | Duration(Days) |
| IM101-102-80-160/W/F | Varicella (Possibly Recurrent)(Moderate) | 117 | Yes | Prednisone5mg | Erythromycin | 10 |
| IM101-031-119-1561/W/F | Varicella(Moderate) | 297 | Yes | Prednisolone10mg | NoneReported | 17 |
| IM101-031-202-1548/W/F | Varicella(Moderate) | 317 | No | NoneReported | Acyclovir | 19 |

- All Cases resolved appropriately per investigator

- 62c - 6

## Measures to Evaluate Effects of Abatacept on the Developing Immune System

| 
10 pups/gender/time point | Postnatal Week 3 | Postnatal Week 7 | Postnatal Week 8 | Postnatal Week 16 |
| --- | --- | --- | --- | --- |
| Abatacept levels | X |  | X | X |
| Anti-abatacept antibodies | X |  | X | X |
| Serum immunogulin levels |  |  | X | X |
| Lymphoid organ weights |  |  | X | X |
| T-dependent antibody response |  | X |  |  |
| Lymphocyte and NK cell phenotypes |  |  | X |  |
| Anti-nuclear antibodies |  |  |  | X |
| Clinical pathology |  |  |  | X |
| Histopathology – lymphoid organs and organs prone to autoimmunity |  |  |  | X |

- 30b - 2

## Effects on Developing Immune System3-Fold Clinical Exposure

| 
10 pups/gender/time point | Postnatal Week 3 | Postnatal Week 7 | Postnatal Week 8 | Postnatal Week 16 |
| --- | --- | --- | --- | --- |
| Abatacept levels | No effect |  | No effect | No effect |
| Anti-abatacept antibodies | No effect |  | No effect | No effect |
| Serum immunogulin levels |  |  | No effect | No effect |
| Lymphoid organ weights |  |  | No effect | No effect |
| T-dependent antibody response |  | No effect |  |  |
| Lymphocyte and NK cell phenotypes |  |  | No effect |  |
| Anti-nuclear antibodies |  |  |  | No effect |
| Clinical pathology |  |  |  | No effect |
| Histopathology – lymphoid organs and organs prone to autoimmunity |  |  |  | No effect |

- 30b - 3

## Effects on Developing Immune System11-fold Clinical Exposure

| 
10 pups/gender/time point | Postnatal Week 3 | Postnatal Week 7 | Postnatal Week 8 | Postnatal Week 16 |
| --- | --- | --- | --- | --- |
| Abatacept levels | No effect |  | No effect | No effect |
| Anti-abatacept antibodies | No effect |  | No effect | No effect |
| Serum immunogulin levels |  |  | No effect | No effect |
| Lymphoid organ weights |  |  | No effect | No effect |
| T-dependent antibody response |  | ♀ 9-foldIncrease |  |  |
| Lymphocyte and NK cell phenotypes |  |  | No effect |  |
| Anti-nuclear antibodies |  |  |  | No effect |
| Clinical pathology |  |  |  | No effect |
| Histopathology – lymphoid organs and organs prone to autoimmunity |  |  |  | Thyroiditis
1/10 ♀ |

**Effects on Developing Immune System****11-fold Clinical Exposure**

- 30b - 4

## Anti-Nuclear and ds-DNA AntibodiesSeroconversion by 6-Month Intervals

- Population: Double-blind, Phase III studies

|  |  | Number (%) of Patients |  |
| --- | --- | --- | --- |
| Anti-nuclear Antibody (ANA) |  | Abatacept | Placebo |
| 6 Months | Baseline Negative Seroconverted | N = 1137
47 (4.1) | N = 575
36 (6.3) |
| 12 Months | Baseline Negative Seroconverted | N = 962
 93 (9.7) | N = 443
48 (10.8) |
| Anti-dsDNA Antibody |  |  |  |
| 6 Months | Baseline Negative Seroconverted | N = 1272
14 (1.1) | N = 629
15 (2.4) |
| 12 Months | Baseline Negative Seroconverted | N = 1062
29 (2.7) | N = 490
23 (4.7) |

- BLA

- 64a - 5

## Antibody Response to VaccinationStudy Design

**Single Dose Study: open-label, randomized, parallel-groups **
**4 treatment groups (20 healthy volunteers per group):**
**Antibody levels evaluated at:**
**Baseline**
**14 days post-vaccination**
**28 days post-vaccination**

|  | Visit Day |  |  |
| --- | --- | --- | --- |
| Treatment Group | 1 | 14 | 56 |
| 1 | V | — | — |
| 2 | V | A | — |
| 3 | A | V | — |
| 4 | A | — | V |
| A = Abatacept 750 mgV = Vaccine |  |  |  |

- IM101-049

- 24 - 3

## EULAR Disease Activity Outcomes (DAS 28 – ESR)Patients with Inadequate Response to Methotrexate

- IM101-102

**6 Months**

**1 Year**

- 	   ** *p* <0.001
- 		LOCF Analysis

- 	Low Disease Activity:	≤ 3.2
- 	Remission:	< 2.6

- **

- **

- **

- **

- 43b - 49

## Mean Values of Biomarkers at 6 MonthsPatients with Inadequate Response to Anti-TNF Therapy

**Mean Values of Biomarkers at 6 Months****Patients with Inadequate Response to Anti-TNF Therapy**

- IM101-029

**TNF-****α**

**IL-6**

**MMP-3**

**Rheumatoid Factor**

**Pro-inflammatory Cytokines **

**Proteolytic Enzyme **

**Autoantibody **

**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 ****Range**

**Normal ****Range**

**B/L = baseline value**

***p***** = 0.019**

***p***** < 0.001**

***p***** < 0.001**

***p***** = 0.014**

- 44b - 67

## Mean Changes in Total Radiographic Scores at 1 YearSubgroup Analysis Patients with Inadequate Response to Methotrexate

- IM101-102

**Abatacept**
**Better**

**Placebo**
**Better**

|  | Abatacept (N) | Placebo (N) |
| --- | --- | --- |
| All Patients | 391 | 195 |
| Duration 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 | 157 |
| Negative | 46 | 25 |
| CRP at Baseline (mg/dL) |  |  |
|  1.2 | 100 | 59 |
| 1.2 – 2.2 | 94 | 48 |
| 2.2 – 4.0 | 92 | 47 |
| > 4.0 | 105 | 41 |
| Swollen Joints |  |  |
| 9-15 | 117 | 49 |
| 16-20 | 97 | 52 |
| 21-27 | 92 | 46 |
| 28-56 | 85 | 48 |
| ACR 20 at Day 169 |  |  |
| Responders | 268 | 79 |
| Non-responders | 102 | 87 |

**Treatment Difference with 95% CI**

**Mean Changes in Total Radiographic Scores at 1 Year****Subgroup Analysis**** ****Patients with Inadequate Response to Methotrexate**

- 43b - 76