Objective: To systematically review the occurrence of malignancies among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) treated with anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in randomized controlled trials (RCTs), and to report a retrospective personal case series evaluating the frequency of malignancies in patients with RA, PsA, and AS requiring anti-TNF therapy selected with more comprehensive cancer screening procedures compared with patients screened according to previously published procedures.
Methods: The primary outcome was the report of frequency of malignancies in RCTs and the latency between the therapy introduction and the occurrence of the neoplasm. A total of 363 consecutive RA, PsA, and AS patients requiring anti-TNF therapy from 2002 to 2006 observed at the Rheumatology Unit in Prato, Italy, underwent extensive cancer screening procedures. An historical controlled group of 73 patients treated between January 1999 and December 2001 underwent the screening procedures accepted for the RCT procedures.
Results: Thirty-six RCTs were included for analysis. Malignancies occurred in 60 (0.75%) of 8,015 patients randomized to the active treatment arm and in 21 (0.52%) of 3,991 patients in the placebo arms (P = 0.15). In the personal retrospective case series, 1 study patient (0.27%) and 3 controls (4.1%) developed cancer over the followup period (P = 0.017). Mean +/- SD followup duration was 40.9 +/- 16.7 months in study patients and 50.6 +/- 18.1 months in controls.
Conclusion: The results of RCTs and our data showing 26% of malignancies occurring within 12 weeks from enrollment suggest the need for a revision of current cancer screening procedures in RCTs and in clinical practice.