ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1695

Prolonged Exposure to Subcutaneous and Intravenous Abatacept in Patients with Rheumatoid Arthritis Does Not Affect Rates of Infection, Malignancy and Autoimmune Events: Results From Pooled Clinical Trial Data

M. C. Genovese1, M C. Hochberg2, R. B. Cohen3, M. E. Weinblatt4, J. Kaine5, Edward Keystone6, P. Nash7, I. Delaet8 and R. Alten9, 1Stanford University, Palo Alto, CA, 2Department of Medicine, University of Maryland, Baltimore, MD, 3Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 4Rheumatology & Immunology, Brigham & Women's Hospital, Boston, MA, 5Sarasota Arthritis Research Center, Sarasota, FL, 6Mount Sinai Hospital, Toronto, ON, Canada, 7University of Queensland, Brisbane, Australia, 8Bristol-Myers Squibb, Princeton, NJ and Bristol-Myers Squibb, Hopewell, VA, 9Schlosspark-Klinik, University Medicine, Berlin, Germany

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy: Safety II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Disease-modifying therapies for RA have proven efficacy, but these drugs may have selective toxicities, such as malignancy, that may increase with duration of treatment. Periodic re-evaluation of incidence rates (IRs) allows assessment of any cumulative or new events over time. Using the largest pool of integrated abatacept clinical trial data to date, we investigated the long-term (LT) safety of subcutaneous (SC) and intravenous (IV) abatacept.1,2 Methods: Data were pooled from the cumulative (double-blind and open-label short-term [ST] and open-label LT extension) periods of 13 clinical studies, including one Phase II and four Phase III trials with SC abatacept,1 and two Phase II and six Phase III trials with IV abatacept.2 IRs for adverse events (AEs), serious AEs (SAEs), infection, malignancy and autoimmune AEs were calculated as events per 100 patient-years (pt-yrs) of exposure (Poisson 95% CI). IRs for the cumulative period were compared with IRs originally estimated from the pooled ST periods of the eight IV abatacept clinical studies.2 Results: A total of 6028 patients received IV or SC abatacept during the cumulative period, with abatacept exposure of 16,670.56 pt-yrs; 1167 patients received abatacept for >5 yrs. IRs of AEs, SAEs, infections or serious infections did not increase in the cumulative relative to ST periods (Table). The most frequently reported serious infections in the cumulative period were pneumonia (IR: 0.43 [0.34, 0.54]), upper respiratory tract infection (0.18 [0.12, 0.26]) and cellulitis (0.15 [0.10, 0.23]). There was no increase in IRs between the ST and cumulative periods for hospitalized, opportunistic or tuberculosis infections. The IRs of overall malignancy, combined lymphomas and lung cancers did not increase in the cumulative versus the ST periods; the most common malignancies in the cumulative period were basal cell carcinoma (IR: 0.46 [0.36, 0.58]), squamous cell carcinoma (IR: 0.15 [0.09, 0.22]), breast cancer (IR: 0.12 [0.07, 0.19]) and squamous cell carcinoma of the skin (0.08 [0.04, 0.14]). The IR of autoimmune AEs during the cumulative period was comparable to the ST period, the most common event being psoriasis (IR: 0.51 [0.40, 0.63]).

Conclusion: Based on the cumulative short-term and long-term exposure of 6028 patients to IV or SC abatacept (16,670.56 pt-yrs), the incidence rates and events reported with long-term abatacept treatment were similar to those reported in the short-term, with no increase in rate for any event with increasing exposure. These findings demonstrate that IV and SC abatacept are both well tolerated over the long-term.

  1Alten R et al. Arthritis Rheum 2011;63(10 Suppl):S150. 2Hochberg M et al. Arthritis Rheum 2010;62(10 Suppl):S164.  

 

ST period
(N=3173)

Cumulative (ST + LT) period (N=6028)

Exposure, pt-yrs

2330.82

16,670.56

AE

386.70 (372.31, 401.51)

213.95 (208.33, 219.68)

SAE

18.10 (16.37, 19.97)

13.24 (12.63, 13.88)

Death

0.51 (0.27, 0.90)

0.60 (0.49, 0.73)

Infection

98.00 (93.20, 102.99)

66.33 (64.33, 68.37)

    Hospitalized

3.33 (2.63, 4.16)

2.37 (2.14, 2.63)

Serious infection

3.68 (2.94, 4.55)

2.57 (2.32, 2.83)

Malignancy

1.55 (1.09, 2.15)

1.35 (1.18, 1.55)

Autoimmune event

2.07 (1.53, 2.75)

1.83 (1.62, 2.05)

Presented are incidence rates, calculated as events/100 pt-yrs (Poisson 95% CI), unless otherwise stated; includes events occurring up to 56 and 60 days post-last dose for Phase III and II studies, respectively; ST=Short-term; LT=Long-term

 

Disclosure:

M. C. Genovese,

Bristol-Myers Squibb,

2,

Bristol-Myers Squibb,

5;

M. C. Hochberg,

Abbott Laboratories, Astra-Zeneca, Bioiberica S.A., Eli Lilly Inc., Genentech/Roche, Merck Inc., Novartis Pharma A.G., Pfizer Inc., Stryker LLC, Xoma.,

5;

R. B. Cohen,

Bristol-Myers Squibb,

5;

M. E. Weinblatt,

Bristol-Myers Squibb,

2,

Bristol-Myers Squibb,

5;

J. Kaine,

Bristol-Myers Squibb,

5,

Bristol-Myers Squibb,

8;

E. Keystone,

Amgen, Janssen, Roche,

2,

Amgen, Janssen, Roche, UCB, Abbott, Lilly, BMS,

5;

P. Nash,

Bristol-Myers Squibb,

2,

Bristol-Myers Squibb,

5,

Bristol-Myers Squibb,

8;

I. Delaet,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3;

R. Alten,

ABBOTT, BMS, GSK,NOVARTIS, PFIZER, UCB,

2.

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