Malignancies and anti-TNF therapy in rheumatoid arthritis: a single-center observational cohort study

Abstract

Inhibitors of tumor necrosing factor alpha (TNF-a) have proven to be highly effective in the treatment of rheumatoid arthritis (RA). Concerns, however, are raised about the possible association between these treatments and an increased development of malignancies. The objective of this paper was to compare the risk of hematologic and solid malignancies in patients treated for RA with anti-TNF therapy, with the risk in the general population. From January 2000 until January 2012, all RA patients that started treatment with anti-TNF agents were included in this single-center cohort study. The primary outcome of this study was the incidence of malignancy after starting anti-TNF treatment. In our cohort of 365 patients, 34 malignancies were discovered in 30 patients after the start of anti-TNF treatment; 20 patients developed a solid malignancy, 6 a hematologic, 2 a solid and a hematologic malignancy, and 2 patients developed 2 solid malignancies. The overall incidence rate (IR) of malignancy was 1379.1 per 100.000 patient years. The risk or standardized incidence ratio (SIR) of solid malignancy, calculated by comparison with the age-adjusted population in Flanders, was 120.1 in female and 136.7 in male patients. The calculated SIR of hematologic malignancy was 450.8 for women and 473.9 for men. Some immune modulation-related lymphoproliferative disorders regressed spontaneously when stopping TNF blockers. Overall, the malignancy risk in our rheumatoid arthritis patients treated with anti-TNF therapy was slightly higher than in the normal population; the risk of hematologic malignancies was more important.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis

“…9 10 14 25 51–55 Both in comparison to the general population and to patients on csDMARDs, patients on bDMARDs did not show an increased risk for malignancies. In a few more recent studies, patients on non-TNFi were also included 9 10.…”

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

“…Of the 29 studies, 21 were registries or cohort studies and 8 were long‐term extensions of RCTs, all using the general population as the comparator for new malignancy incidence (Table ).…”

“…The estimate used for comparing the risk of malignancy between anti‐TNF users and the general population was SIR in 19 studies, hazard ratio in 2 studies, and relative risk in 4 studies …”

“…Among the remaining 21 articles, 11 said that malignancies before the anti‐TNF use had been excluded and 4 articles did not specify this issue at all. Finally, 6 articles gave the number of patients with malignancies before anti‐TNF use . In 5 of these studies, the frequency of these patients ranged from 0.5% to 3.5% of the total cohort.…”

Infection, malignancy, switching, biosimilars, antibody formation, drug survival and withdrawal, and dose reduction

“…In a national registry study [11 & ] and a literature-based review [13], there was no signal noted between TNFi and malignancy incidence. However, a single center study by Berghen et al [17] noted that malignancies (both solid tumor and hematologic) after starts of anti-TNF treatment were found to be higher than normal population. Some lymphoproliferative disorders regressed when TNF blockers were stopped.…”