403 - Safety Profile of Subcutaneous Abatacept Focusing on Clinically Relevant Events in Patients with Rheumatoid Arthritis (RA) and up to 4.5 Years of Exposure

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Rieke Alten1, Jeffrey L. Kaine2, Edward Keystone3, Peter T. Nash4, Ingrid Delaet5, Keqin Qi5 and Mark C. Genovese6, 1Rheumatology Schlossparkklinik, Berlin, Germany, 2Sarasota Arthritis Center, Sarasota, FL, 3Mount Sinai Hospital, Toronto, ON, 4University of Queensland, Brisbane, Australia, 5Bristol-Myers Squibb, Princeton, NJ, 6Stanford University Medical Center, Palo Alto, CA
Presentation Number: 403

Background/Purpose: Biologic therapies for RA can increase the risk of some safety events such as infections, autoimmune events and malignancies. Furthermore, with subcutaneous (SC) biologics, some patients (pts) may experience injection site reactions (ISRs), such as burning and stinging1. Integrated analyses of clinical trial data are important to monitor these events over the long term. Here, we investigate such events using integrated clinical trial data of SC abatacept in a large group of pts with RA refractory to traditional DMARDs.

Method: Data from the short- and long-term periods of five SC abatacept RA clinical trials were pooled; one Phase IIa and two Phase IIIb randomized controlled trials (ACQUIRE, ALLOW), and two Phase IIIb open-label studies (ATTUNE, ACCOMPANY). Safety events were assessed for pts who received ≥1 dose of SC abatacept (125 mg/week fixed dose). Overall and 6-mthly (up to Mth 24) incidence rates (IRs) were calculated as number of patients with events per 100 patient–years (p–y) of exposure, with 95% confidence intervals (CIs). IRs post Mth 24 not shown due to low pt numbers at time of data analysis.

Result: The analysis included 1879 pts with 3086 p–y of exposure. Mean (range) exposure was 20 (2–56) mths; 1191 pts had >18 mths of exposure. Serious infections occurred at an IR (95% CI) of 1.94 (1.50–2.50), in 59 (3.1%) pts; the most frequent (IR>0.10) were pneumonia (0.36 [0.20–0.65]), urinary tract infection (0.16 [0.07–0.39]) and gastroenteritis (0.13 [0.05–0.35]). TB, pulmonary TB and peritoneal TB were recorded in one pt each (0.03 [0.00–0.23] each). Malignancies excluding non-melanoma skin cancer occurred at an IR of 0.68 (0.45–1.05) in 21 (1.1%) pts. The most frequent (IR>0.10) malignancies were basal cell carcinoma (0.46 [0.27–0.77]), breast cancer and squamous cell carcinoma of skin (0.16 [0.07–0.39] each). Autoimmune events occurred with an IR of (1.28 [0.93–1.75]) in 39 (2.1%) pts. The most frequent (IR>0.10) autoimmune events were psoriasis (0.29 [0.15–0.56]) and Sjögren’s syndrome (0.19 [0.09–0.43]). IRs of serious infections, malignancies and autoimmune events did not increase with increasing exposure (Table). ISRs occurred with an IR of (2.22 [1.74–2.82]) in 66 (3.5%) pts; the most frequent were erythema, hematoma, pain and pruritus (0.46 [0.27–0.77] each). Events were mostly (94%) mild in intensity; two pts discontinued due to ISRs. ISRs mainly occurred during the first 6 mths (Table).

 

Incidence rates of events in pts receiving SC abatacept (N=1879)

Mths

0–6

6–12

12–18

18–24

Serious infections*

2.42 (1.60–3.68)

n=22

2.12 (1.33–3.36)

n=18

1.28 (0.66–2.46)

n=9

1.51 (0.68–3.36)

n=6

Malignancies excl. NMSC

0.44 (0.16–1.17)

n=4

1.17 (0.63–2.17)

n=10

0.56 (0.21–1.49)

n=4

0.25 (0.03–1.75)

n=1

Autoimmune events

1.54 (0.91–2.60)

n=14

0.94 (0.47–1.87)

n=8

0.99 (0.47–2.08)

n=7

1.75 (0.84–3.68)

n=7

Total ISRs

5.59 (4.24–7.38)

n=50

0.72 (0.32–1.59)

n=6

1.30 (0.68–2.50)

n=9

0

*Subset of serious adverse events; Pre-specified based on a list of MedDRA preferred terms; Data are IR (95% CI); NMSC=non-melanoma skin cancer; ISR=injection site reaction; Mths 0–6 is Day 1–Day 180, Mths 6–12 is Day 181–Day 360, Mths 12–18 is Day 361–Day 540, Mths 18–24 is Day 541–Day 720

Conclusion: 

These pooled safety data, from 1879 pts with up to 4.5 yrs of treatment and 3086 p–y of exposure, demonstrate that long-term treatment with SC abatacept is well tolerated, and does not lead to an increase in infections, malignancies or autoimmune events over time. ISRs were generally mild and infrequent. Data presented here are consistent with observations for IV abatacept1.

1Curtis JR, et al. Curr Med Res Opin 2011;27:71–8

2Hochberg M, et al. Arthritis Rheum 2010;62:S164


Keywords: abatacept and clinical trials

Disclosure: R. Alten, Bristol-Myers Squibb, Merck Pharma GmbH, Wyeth Pharmaceuticals, Pfizer, 2, Abbott Laboratories, Bristol-Myers Squibb, Horizon Pharma, Merck Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, 8, Abbott Laboratories, Horizon Pharma, Merck Pharma GmbH, Nitec Pharma GmbH, Novartis Pharmaceuticals Corporation, Roche, 5, Abbott Laboratories, Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, Roche, 6 ; J. L. Kaine, Amgen Inc., Bristol-Myers Squibb, Novartis Pharmaceuticals Corporation, UCB, Inc., 8, Bristol-Myers Squibb, 2 ; E. Keystone, Abbott Laboratories, Amgen Inc; AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Centocor Inc, F. Hoffmann-LaRoche Inc, Genzyme, Merck, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, UCB, 2, Abbott Laboratories, AstraZeneca Pharmaceuticals LP, Biotest, Bristol-Myers Squibb, Centocor Inc, F. Hoffmann-LaRoche Inc, Genentech Inc, Merck, Nycomed, Pfizer Pharmaceuticals, UCB, 5, Abbott Laboratories, Bristol-Myers Squibb, F. Hoffmann-LaRoche Inc, Merck, Pfizer Pharmaceuticals, UCB, 8 ; P. T. Nash, Bristol-Myers Squibb, 5, Bristol-Myers Squibb, 2, Bristol-Myers Squibb, 8, Bristol-Myers Squibb, 9 ; I. Delaet, Bristol-Myers Squibb, 1, Bristol-Myers Squibb, 3 ; K. Qi, Bristol-Myers Squibb, 3 ; M. C. Genovese, Bristol-Myers Squibb, 5 .