Context: Interest exits in whether TNF-alpha antagonists increase the risk of breast cancer and totalmalignancies in patients with rheumatoid arthritis (RA).
Objectives: To analyze the risk of malignancies, especiallybreast cancer, in patients with RA enrolled in randomized control trials (RCTs).
Methods: A systematic literaturesearch for RCTs from 1 January 1998 to 1 July 2013 from online databases, such as PubMed, WILEY, EMBASE,ISI web of knowledge and Cochrane Library was conducted. Studies included RCTs that compared the safetyof at least one dose of the five TNF-α antagonists with placebo or methotrexate (MTX) (or TNF-α antagonistsplus MTX vs placebo plus MTX) in RA patients for more than 24 weeks and imported all the references intodocument management software EndNote×6. Two independent reviewers selected studies and extracted the dataabout study design, patients’ characteristics and the type, number of all malignancies.
Results: 28 RCTs from34 records with 11,741 patients were analyzed. Of the total, 97 developed at least one malignancy during thedouble-blind trials, and breast cancer was observed in 17 patients (17.5% of total malignancies). However, therewas no statistically significant increased risk observed in either the per protocol (PP) model (OR 0.65, 95%CI[0.22, 1.93]) or the modified intention to treat (mITT) model (OR 0.75, 95%CI [0.25, 2.21]). There were alsono significant trend for increased risk of total malignancies on anti-TNF-α therapy administered at approveddoses in either model (OR, 1.06, 95%CI [0.64, 1.75], and OR, 1.30, 95%CI [0.80, 2.14], respectively). As to thetwo models, modified intention to treat model analysis led to higher estimation than per protocol model analysis.
Conclusions: This study did not find a significantly increased risk of breast cancer and total malignancies inadults RA patients treated with TNF-α antagonists at approved doses. However, it cannot be ignored that morepatients developed malignancies with TNF-α antagonists therapy compared with patients with placebo or MTX,in spite of the lack of statistical significance, so that more strict clinical trials and long-term follow-up are needed,and both mITT and PP analyses should be used in such safety analyses.