Assessing the possible association of anti‐TNF use with new malignancies: A neglected methodological consideration

Abstract

Purpose Whether anti‐TNF agents increase, malignancy risk remains debated. The potential problems with comparing the number of observed malignancies in anti‐TNF treated cohorts to number of expected malignancies in national cancer registries could have been an important issue. National registries give expected number of malignancies per organ involved regardless of if this is a secondary or a higher malignancy while anti‐TNF agents are not or are sparingly used in patients with an existing or history of a malignancy. This results in a biased standardized incidence ratio (SIR). We aimed to formally look at the presence and the magnitude of this bias in published work. Methods A systematic search was performed in PUBMED/MEDLINE about anti‐TNF use in rheumatoid arthritis (RA) up to July 2016. The main outcome sought was malignancy incidence in a RA cohort as compared with that in the general population. Randomized controlled trials, meta‐analyses, and articles published in languages other than English were excluded. Results The potentially biased SIR was discussed in only 1 of 29 studies we analyzed, while in none of these studies, the authors highlighted this as a limitation. We were able to approximate the pooled SIR for overall malignancy in 12 studies before and after correcting for this bias. It was 0.89 (CI: 0.84‐0.95) before and increased to 1.05 (CI: 0.99‐1.11), when corrected. Conclusion Planning and assessment of studies investigating malignancy incidence possibly related to anti‐TNF use in RA, and probably in other diseases, should take into consideration the described bias in SIR calculations.

Risk of cancer after long-term therapy of autoimmune disorders with glucocorticoids or DMARDs—a controversial issue

“…However, uncertainty remains because of the fact that even recent studies (prospective trials and population-based trials) failed to confirm a strict correlation with increased risk for malignancies [1,7]. Another confounding factor is defined by increased disease activity that strongly correlates with lymphoma risk [15] especially in case of RA. A group of Korean researchers tried to estimate the incidence of malignancy in early RA patients and to evaluate the relative risk of malignancy by using the Korean National Claims Database comprising a total of 14,081 identified patients.…”

Recommendations in the American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis Related to the Use of Biologic Agents in Patients With a History of Cancer Need Reconsideration: Comment on the Article by Singh et al

“…Based on observational studies comparing the observed cancer incidence in an RA cohort with that reported in a national cancer registry, it has also been stated that treatment with a biologic agent does not appreciably increase the incidence of neoplasms among RA patients (5,6). However, as we recently pointed out, there has been a common methodologic error in such comparisons (7). There are 3 important considerations.…”