Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis

ABSTRACT

Introduction: Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents.

Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment. Data on cancer occurrence were extracted at the maximum follow-up time reported.

Expert opinion: Fifty-five RCTs with 20,631 patients met the eligibility criteria. Of these, 32 trials with 15,539 patients reported at least one case of cancer, for a total of 112 malignancies. The degree of variability between studies was consistent with what would be expected to occur by chance alone. There was no evidence of an association between anti-TNF agents and cancer risk (fixed-effects model (OR: 1.31, 95% CI: 0.89, 1.95); a random-effects model (OR: 1.16, 95% CI: 0.75, 1.81)). We found evidence of selective outcome reporting or publication bias suggesting that the pooled effect estimate for cancer may have been overestimated. The evidence is imprecise, and the risk of bias was high or unclear across primary studies.

KEYWORDS:

• Adverse events
• ankylosing spondylitis
• anti-TNF drugs
• cancer
• drug safety
• malignancy
• meta-analysis
• psoriatic arthritis
• rheumatoid arthritis
• systematic review

Article highlights

• Malignancies have been reported in rheumatologic patients treated with anti-TNF agents. The potential association between anti-TNF drugs and cancer remains unclear.

• The authors conducted a systematic review and meta-analysis of published trials involving patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis to determine the effect of anti-TNF agents on cancer risk.

• Fifty-five RCTs with 20,631 patients met the eligibility criteria and reported cancer occurrence as a secondary endpoint. Among these, 32 trials involving 15,539 patients reported at least one cancer case (for a total of 112 malignancies) and were included in the meta-analysis.

• Quantitative synthesis of the available epidemiological evidence does not support the hypothesis that the use of anti-TNF drugs significantly affects cancer risk, at least in the short term.

• Given the increasing use of TNF inhibitors in adult patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, it is important to continue monitoring their long-term safety profiles through complementary sources of research data (such as registries and long-term epidemiological studies).

Acknowledgments

We are grateful to Antonio Spadaro who participated in the early phase of this study. Unfortunately, he passed away before seeing the completion of the review.

Declaration of interest

Valentina Marino is an employee of Pfizer Italia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This study was supported by an unrestricted grant from Pfizer Italia through a service agreement with Health Publishing & Services Srl. Health Publishing & Services Srl supports research activities at the IRCCS Galeazzi Orthopedic Institute and the IRCCS Mario Negri Institute for Pharmacological Research.