麻豆传媒

Anti-tumor necrosis factor (TNF)-α therapy was not associated with recurrent or new primary cancers in inflammatory disease patients with previous cancer, a study in a Danish population cohort found. Nor did the timing of anti-TNF-α therapy after initial cancer diagnosis influence cancer development.

The incidence of recurrent or new primary cancer was 30.3 cases (95% CI 24.0-38.2) per 1,000 person-years in patients receiving anti-TNF-α treatment and 30.4 cases (31.7–37.3) per 1,000 person-years in the control group, for an adjusted hazard ratio of 0.82 (95% CI 0.61-1.11), reported Akbar K. Waljee, MD, MSc, of the University of Michigan in Ann Arbor, and colleagues.

As shown in their study online in the , during 18,752 person-years (median 5.6 years, interquartile range [IQR] 2.8-7.9) of follow-up, 635 individuals developed recurrent or new primary cancers, 72 of whom had received TNF inhibition and 563 of whom were in the control group.

That translated to five recurrent cancers and 25.2 new primary malignancies per 1,000 person-years in anti-TNF-α recipients and six and 28.4 per 1,000 person-years in control patients.

The median time between treatment and recurrent or new primary cancer diagnosis was 2.8 years (IQR 1.7-5.4).

"Our study shows promising results for safety of anti-TNF-α therapy among people who had a primary cancer diagnosis, which are much needed to help to guide patients and clinicians in making day-to-day decisions on the risks and benefits of initiating treatment with anti-TNF-α therapy in the setting of active IBD [inflammatory bowel disease], rheumatoid arthritis, or psoriasis," the researchers wrote.

Overall, the study identified 25,738 adult patients with immune-mediated disease and a history of cancer. Diagnosed from January 1, 1999 through December 31, 2016, the patients were recruited from the prospectively recorded Danish National Patient Registry and the Danish Cancer Registry. Of these individuals, 434 who received TNF inhibition after their initial cancer were matched to 4,328 patients in an unexposed control group.

About 68% in both groups were women, but those in the exposure group were somewhat younger at the time of initial cancer diagnosis: 55.4 vs 63.1 years. The most common initial malignancy type was skin (52% in both groups), followed by female genital (about 14%) and breast (9.4%).

This group was also approximately 6 years younger at the time of their inflammatory disease diagnosis, suggesting they were at higher risk of disease-related complications, the researchers explained.

Immune-mediated diseases across the two groups included rheumatoid arthritis (about 55.6%), psoriasis (16.5%), and IBD (about 35%).

The authors noted that clinicians are concerned about the risk of promoting cancer recurrence when prescribing anti-TNF-α agents to patients with a history of cancer. That often results in avoidance of the therapy and poorly controlled disease in a growing population of patients with a previous cancer and a current immune-mediated disease.

Earlier this year Scandinavian researchers similarly reported no increased cancer risk in psoriatic arthritis patients taking TNF inhibitors.

In a that accompanied the study by Waljee and colleagues, Berkeley N. Limketkai, MD, PhD, of the David Geffen School of Medicine at UCLA, said the findings complement suggesting that the risk of cancer after anti-TNF-α treatment might not be as high as previously suspected and may help allay patient fears about initiating the therapy and result in better quality of life.

"The findings are compelling and encouraging, but it is worth noting that the quality of the overall body of evidence is still low," Limketkai wrote, adding that more investigation is needed to confirm the findings and progressively increase the overall grade of evidence.

"Although these findings might be reassuring, physicians still need to discuss and be vigilant about the potential risk of malignancy, albeit low, from the initiation of biological therapies. The patient still needs to consider and accept the calculated risks before proceeding with biological therapy," the commentator said.

Also commenting on the study, Bo Shen, MD, PhD, of NewYork-Presbyterian/Columbia University Irving Medical Center in New York City, who was not affiliated with the study, said its main strength was the utilization of the prospectively maintained national registries with an adequate sample size to address the research question in general.

"The results certainly will give some relief for concerned practitioners," he told 麻豆传媒. He cautioned, however, that like most population-based registries, the study database had inherent shortcomings, such as the lack of detailed information on variables such as smoking, sun exposure, family history of cancer, concurrent cancer-prone diseases, history of cancer-reducing procedures, the stage of various cancers, dosage or duration of anti-TNF-α agents, and duration of immunomodulators.

"It would be helpful to delineate each patient variable in the multivariable analyses," Shen added. "It would also be interesting to see if the exposure to anti-TNF agents might be associated with a decreased risk for colitis-associated cancer in the IBD subpopulation." He emphasized that close cancer screening and surveillance along with monitoring of inflammatory disease activity are still needed in patients on long-term TNF inhibitors.

Study limitations, the authors said, included that it was not possible to rule out the development of delayed recurrent or new primary cancers or persistent initial cancers that might influence the prescription of anti-TNF treatment. It was also not possible to control for cancer stage, which might have confounded the results since lower-stage cancers are less likely to recur, the team explained. And although the study addressed confounding factors such as disease severity and matched anti-TNF patients to controls, some immeasurable confounders might have persisted. Furthermore, patients who received therapy were at higher risk of disease-related complications than unexposed patients.

Additionally, the researchers noted, the study was unable to control for the exact cancer diagnosis, the cancer recurrence risk, the effects of recurrent or new primary cancer development according to the duration of anti-TNF-α exposure, or according to specific agents because of the significant loss in statistical power.