Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Dec;68(12):1819-26.
doi: 10.1136/ard.2008.097527. Epub 2008 Dec 3.

Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment

T A Simon  1 , A L Smitten, J Franklin, J Askling, D Lacaille, F Wolfe, M C Hochberg, K Qi, S Suissa
Affiliations

Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment

T A Simon et al. Ann Rheum Dis. 2009 Dec.

Abstract

Objective: To provide context for the malignancy experience in the rheumatoid arthritis (RA) abatacept clinical development programme (CDP) by performing comparisons with similar RA patients and the general population.

Methods: Malignancy outcomes included total malignancy (excluding non-melanoma skin cancer (NMSC)), breast, colorectal, lung cancers and lymphoma. Comparisons were made between the observed incidence in patients within the abatacept CDP and RA patients on disease-modifying antirheumatic drugs (DMARD) identified from five data sources: the population-based British Columbia RA Cohort, the Norfolk Arthritis Register, the National Data Bank for Rheumatic Diseases, the Sweden Early RA Register and the General Practice Research Database. Age and sex-adjusted incidence rates (IR) and standardised incidence ratios (SIR) were used to compare events in the abatacept trials with the RA DMARD cohorts and the general population.

Results: A total of 4134 RA patients treated with abatacept in seven trials and 41,529 DMARD-treated RA patients in the five observational cohorts was identified for study inclusion. In the abatacept-treated patients, the 51 malignancies (excluding NMSC), seven cases of breast, two cases of colorectal, 13 cases of lung cancer and five cases of lymphoma observed were not greater than the range of expected cases from the five RA cohorts. The SIR comparing RA patients with the general population were consistent with those reported in the literature.

Conclusions: The IR of total malignancy (excluding NMSC), breast, colorectal, lung cancers and lymphoma in the abatacept CDP were consistent with those in a comparable RA population. These data suggest no new safety signals with respect to malignancies, which will continue to be monitored.

PubMed Disclaimer

Conflict of interest statement

Competing interests: Declared. TAS and KQ are current full-time employees of Bristol-Myers Squibb. ALS is currently a full-time employee of Bristol-Myers Squibb but her affiliation at the time the work was done was the School of Medicine, Duke University, Durham, NC, USA. JA reports having been an invited speaker at meetings sponsored by Schering-Plough and Abbott. JF reports having received research funding from Bristol-Myers Squibb. DL reports receiving research funding from Bristol-Myers Squibb to perform the analyses included in the manuscript and has participated in advisory meetings supported by Bristol-Myers Squibb. DL is supported by an investigator award from the Arthritis Society of Canada and is the Nancy and Peter Paul Saunders Scholar. FW reports having received research grants from Bristol-Myers Squibb, Centocor, Abbott and Amgen. MCH reports serving as a consultant to Amgen, Bristol-Myers Squibb and Roche. SS reports having served as an advisor and participating as a speaker in scientific meetings for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Pfizer and Sepracor. SS also reports receiving research funding from AstraZeneca and GlaxoSmithKline.

Figures

Figure 1
Figure 1
Standardised incidence ratios (SIR) of malignancies in the abatacept cumulative study periods compared with the observational rheumatoid arthritis disease-modifying antirheumatic drug cohorts. Values represent SIR and 95% CI. (A) Total malignancy (excluding non-melanoma skin cancer); (B) Breast cancer; (C) Colorectal cancer; (D) Lung cancer; (E) Lymphoma. BC, population-based British Columbia RA Cohort; GPRD, General Practice Research Database; NDB, National Data Bank for Rheumatic Diseases; NOAR, Norfolk Arthritis Register; RCT, randomised controlled trial; Sweden ERA, Sweden Early Rheumatoid Arthritis Register.
Figure 2
Figure 2
Standardised incidence ratios (SIR) of malignancies in the abatacept cumulative study periods compared with the general population (Surveillance Epidemiology and End Results (SEER)). The lines indicate the SIR point estimates and 95% CI for abatacept compared with the general population (SEER). The diamonds represent SIR reported in the literature that compare rheumatoid arthritis (RA) patients with non-RA patients or general populations. *One study had no observed cases of lung cancer; the SIR is not presented in the figure. RCT, randomised controlled trial.
See this image and copyright information in PMC

References

    1. Tan P, Anasetti C, Hansen JA, et al. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med 1993;177:165–73 - PMC - PubMed
    1. Kremer JM, Westhovens R, Leon M, et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med 2003;349:1907–15 - PubMed
    1. Kremer JM, Genant HK, Moreland LW, et al. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med 2006;144:865–76 - PubMed
    1. Genant HK, Peterfy CG, Westhovens R, et al. Abatacept inhibits structural damage progression in rheumatoid arthritis: results from the long-term extension of the AIM trial. Ann Rheum Dis 2008;67:1084–9 - PMC - PubMed
    1. Genovese MC, Schiff M, Luggen M, et al. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-TNF therapy. Ann Rheum Dis 2008;67:547–54 - PubMed

Publication types

MeSH terms