Cancer Risk Slightly Higher Among Patients Treated With Abatacept
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Although the risks for specific cancers and infections were similar between abatacept and other biologic and targeted synthetic DMARDs among patients with rheumatoid arthritis, a slight increase in total cancer risk associated with the drug requires additional research, according to data published in Arthritis Research & Therapy.
“Clinical trials are smaller and include a select population of patients who fulfil inclusion and exclusion criteria and while the results are internally valid, they are often not externally valid, or generalizable, to the entire population of patients with the disease, particularly those with comorbidities,” Teresa A. Simon, MPH, who was director of global pharmacovigilence and epidemiology at Bristol-Myers Squibb during the study, told Healio Rheumatology. “Generally, a large diverse population exposed to a medication provides a more stable estimate compared to smaller studies.”
Simon has since left Bristol-Myers Squibb and is now owner and epidemiology consultant at Physicians Research Center, based in New Jersey.
“This is the largest real-world study to evaluate the safety of abatacept,” Simon added. “It is also one of the first studies to apply a common data model structure to three different data sources. This is a more efficient process to analyze several large datasets simultaneously and a method adopted by the FDA Sentinel Initiative.”
To examine the risks for cancers and infections among patients with RA treated with either abatacept (Orencia, Bristol-Myers Squibb) or other biologic and targeted synthetic DMARDs in a real-world setting, Simon and colleagues conducted a retrospective, observational study of three U.S. administrative health care databases — MarketScan, PharMetrics and Optum. The researchers included adult patients with RA who started abatacept or other biologic and targeted synthetic DMARDs from July 1, 2006, to Sept. 30, 2014, as well as at least 180 days of continuous health plan enrollment prior to the index date.
The researchers included approximately 37,000 patients who initiated abatacept — about 19,200 from MarketScan, 13,600 from PharMetrics and 4,200 from Optum — as well as 109,900 who started other biologic and targeted synthetic DMARDs — 55,300 from MaretScan, 40,800 from PharMetrics and 13,800 from Optum.
For both groups, Simon and colleagues calculated age-stratified incidence rates for total malignancy and hospitalized infections. In addition, propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios for total malignancy, lung cancer, lymphoma, breast cancer, nonmelanoma skin cancer (NMSC), hospitalized infections, opportunistic infections and tuberculosis, both within individual databases and in meta-analyses across the all three.
According to the researchers, incidence rates for total malignancy and hospitalized infections were similar between abatacept and other treatments across all age groups. However, in the meta-analyses, the total malignancy risk of abatacept was slightly, but statistically significantly, increased (HR = 1.09; 95% CI, 1.02-1.16) compared with other biologic and targeted synthetic DMARDs.
“We observed a small but significant increase in overall malignancy, but not for specific malignancies,” Simon said. “There was no single malignancy type that contributed to this increase. We cannot rule out residual confounding especially from the extensive prior exposure to biologics among abatacept users.”
The researchers also observed small, yet not statistically significant, increased risks for lung cancer (HR = 1.1; 95% CI, 0.62-1.96), lymphoma (HR = 1.27; 95% CI, 0.94-1.72), breast cancer (HR = 1.15; 95% CI, 0.92-1.45) and non-melanoma skin cancer (HR = 1.1; 95% CI, 0.93-1.3). There was no significant increase in the risks for hospitalized infections (HR = 0.96; 95% CI, 0.84-1.09) or opportunistic infections (HR = 1.06; 95% CI, 0.96-1.17). Low event counts precluded a meta-analysis for tuberculosis.
“These results, combined with the results from multinational studies in RA registries presented in a EULAR 2019 oral presentation, provide confidence to the prescriber and patients treated with abatacept that that abatacept does not increase the risk of hospitalized infections and specific malignancies compared with other biologics,” Simon said. “These data are consistent with the known safety profile of abatacept.” – by Jason Laday
Disclosure: The authors report funding from Bristol-Myers Squibb. Simon reports being an employee and shareholder of Bristol-Myers Squibb. Please see the study for all other authors’ relevant financial disclosures.
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David A. McLain, MD, FACP, FACR
More drug safety data is always appreciated in clinical practice. In this retrospective study of 166 million insured patients, the researchers identified 37,000 patients who received abatacept and 109,900 patients who received other biologic and targeted synthetic (b/ts) DMARDs between 2006 and 2014.
After analyzing the incidence of malignancy, specific malignancies, hospitalized and opportunistic infections between the two groups, the researchers found no significant increase in hospitalized infections or opportunistic infections with either arm. Yet researchers did note that there was a slight, but significant, increase in total malignancy risk with abatacept vs. the b/ts DMARDs. For specific cancers — including breast cancer, lung cancer, lymphoma and nonmelanoma skin cancer — there was a small, but not significant, increased risk with abatacept.
These results are reassuring for us using abatacept in practice. However, the researchers suggest that this slight risk of malignancy linked to abatacept needs further study.
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