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In the Dec 3, 2008 online issue of The Annals, Simon et al did a comparison of the rate of cancers occurring in the rheumatoid arthritis (RA) abatacept clinical development program with malignancies occurring in five observational RA cohorts (1). The main result of this study is that the rate of cancers in patients included in the clinical trials of abatacept is the same than in RA cohorts.
This type of comparison, presented in figure 1, deserves a major concern. As the authors themselves state, the patients included in the seven abatacept trials were selected, like all patients in trials. For example, in five of these trials mammography was advised before inclusion and patients with suspicious mammography were excluded. In contrast, patients included in RA cohorts are not selected patients.
The selection of patients with a low risk of cancer in RA clinical trials has been well demonstrated in the placebo groups of randomized clinical trials with anti TNF therapy. In the meta-analysis by Bongartz et al. of randomized clinical trials with infliximab and adalimumab, the rate of cancers in the placebo groups was eight times lower than expected in the general population of same age and sex (2, 3). In a meta-analysis of randomized control trials of infliximab performed by the US food and drug
administration, the rate of cancers was five times lower in the placebo groups than expected in the general population of same age and sex (4).
Therefore, the only valid comparison is the comparison of the rate of cancer between abatacept-treated patients and placebo-treated patients in the randomized control trials. The authors did this comparison and did not find any difference. Even with the limitation of a much lower number of patients in the placebo groups (989 patients and 794 patients-years versus 4134 patients and 8388 patient-years in the abatacept groups), this result is the most important of the study and should be emphasized instead of the comparison with the patients included in cohorts.
Number of registries all over the world include patients treated with abatacept, some of them dedicated to patients treated with this drug and, in the next future, it will be possible to compare the rate of cancers
occurring in these patients in comparison with other RA patients included in cohorts.
1. Simon TA, Smitten AL, Franklin J, Askling J, Lacaille D, Wolfe F, et al. Malignancies in the rheumatoid arthritis abatacept clinical development program: An epidemiological assessment. Ann Rheum Dis 2008 Dec
3 [Epub ahead of print].
2. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis
of rare harmful effects in randomized controlled trials. Jama 2006;295:2275-2285.
3. Dixon W, Silman A. Is there an association between anti-TNF monoclonal antibody therapy in rheumatoid arthritis and risk of malignancy and serious infection? Commentary on the meta-analysis by Bongartz et al.
Arthritis Res Ther 2006;8:111.
4. Okada SK, Siegel JN. Risk of serious infections and malignancies with anti-TNF antibody therapy in rheumatoid arthritis. Jama 2006;296:2201-2.