TNF inhibitors do not increase solid cancer risk in PsA
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There is no increased risk for solid cancer, or eight common cancer types, among patients with psoriatic arthritis who receive TNF inhibitors, according to data published in Rheumatology.
“TNF inhibitor (TNFi) is a mainstay in the management of several inflammatory conditions, including PsA,” Karin Hellgren, MD, PhD, of the Karolinska Institute and Karolinska University Hospital, in Stockholm, and colleagues wrote. “As TNF links to essentially all steps involved in carcinogenesis, there have been concerns that TNFi may lead to increased cancer incidences. However, most studies evaluating this association in RA or in inflammatory bowel disease (IBD) have not reported increased cancer risks overall compared with patients not treated with TNFi.”
“Previous studies evaluating TNFi treatment in PsA have so far not reported any overall increased risk of cancer,” they added. “Reports on risks for specific cancer types are, however, scarce and limited in precision and time of follow-up. In addition, previous data have suggested that risk of cancer may differ by type of TNFi agent given their different mechanisms of action. Risk assessments of cancer by TNFi agent in PsA are lacking.”
To examine whether TNF inhibitors are associated with an increased risk for solid cancer in patients with PsA, Hellgren and colleagues conducted a cohort study of data from five Nordic rheumatology registers. These included the Swedish SRQ-ARTIS, the Danish DANBIO, the Norwegian NOR-DMARD, the Finnish ROB-FIN and the Icelandic ICEBIO. In all, the researchers identified 9,655 patients with PsA who initiated a first TNF inhibitor during the study period, defined as 2001 to 2017.
The researchers also identified two disease comparator cohorts, both made up of patients with PsA who were not treated with biologics — one with 14,809 patients from the Nordic registries and the other with 31,350 individuals from national patient registries in Sweden and Denmark. Information on the incidence of solid cancer overall, as well as for eight common cancer types, was collected by linking data to national cancer registries. The included cancer types were colorectal, female breast, lung, prostate, corpus uteri, liver, pancreas and brain.
The researchers used Cox regression to estimate hazard ratios — per country and pooled — among patients who received TNF inhibitors compared with those not treated with biologics, adjusting to age, sex, calendar period, comorbidities and disease activity. Hellgren and colleagues also analyzed standardized incidence ratios in patients treated with TNF inhibitors, compared with the general population.
According to the researchers, 296 solid cancers were recorded among patients with PsA treated with TNF inhibitors, across 55,850 person-years. The pooled, adjusted hazard ratios for solid cancer overall among those who received TNF inhibitors was 1 (95% CI, 0.9-1.2), compared with those who were biologic-naïve from the Nordic registries, and 0.8 (95% CI, 0.7-1), compared with those who were biologic-naïve from the Swedish and Danish national patient registries.
The researchers found no significantly increased risk for any of the included cancer types. The pooled standardized incidence ratios for solid cancer overall among those treated with TNF inhibitors was 1 (95% CI, 0.9-1.1) compared with the general population.
“Our large Nordic study suggests that use of TNFi therapy in patients with PsA is not associated with increased risks of solid cancer overall, nor for eight cancer types,” Hellgren and colleagues wrote. “There were no indications of different crude incidence of solid cancers overall by TNFi agent. The findings are consistent with results on this association from other chronic inflammatory diseases and are of clinical importance for risk communication with patients.”
Perspective
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This study further confirms my gratefulness to the great minds that design, conduct, analyze and publish these much-needed studies. It also impresses on me the ongoing need for all of us in rheumatology to include our patients in registries. It is through these long-term registries and robust studies that we continue to further our understanding of rheumatological diseases and our fast-evolving treatment paradigms.
Studies like this help us better provide our patients with information that will further their understanding of their disease, which will hopefully enable them to more actively participate in shared decision-making in the rheumatology office. TNF inhibitors have been, and continue to be, a mainstay in the treatment of PsA; it is reassuring to be able to be able to share with our patients that yet another study has indicated no significant increased risk for solid tumors.
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
A major concern of patients, after reading the package insert for TNF inhibitors, is the risk of cancer. While lymphoma is the one that is highlighted, there is concern with solid tumors because of the role of TNF in being able to attack tumors.
There is a paradox with TNF, however, as it shows antitumor activity but, alternatively, has been implicated in both cancer development and progression. TNF might be the link between chronic inflammation and the subsequent development of malignant disease. Deregulated TNF expression within the tumor microenvironment appears to favor malignant cell tissue invasion, migration and ultimately metastasis formation.
On the other side, TNF clearly possesses antitumor effects not only in preclinical models, but also in the clinical setting. Several inflammatory conditions are associated with excess risks of specific cancer types: for example, lung cancer and lymphoma in RA, lymphoma, skin cancer and lung cancer in psoriasis and colorectal cancer in IBD. However, most studies evaluating this association of TNF inhibitors in RA or in IBD have not reported increased cancer risks overall compared with patients not treated with TNF inhibitors. The present study is the largest to date to find a lack of association of TNF inhibitors and solid tumors in PsA.
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