Biologics Not Linked to Higher Cancer Risk in RA

Janis C. Kelly

September 25, 2017

Overall cancer risk in patients with rheumatoid arthritis (RA) treated with biologic disease-modifying antirheumatic drugs (bDMARDs) is no greater than in those treated with conventional synthetic DMARDS (csDMARDs), a prospective cohort study of 70,000 patients found.

Hjalmar Wadström, MD, and colleagues report their findings in an article published online September 18 in JAMA Internal Medicine.

They found no significant increase in overall cancer risk for patients with RA treated with short-term to medium-term tumor necrosis factor inhibitors (TNFis), tocilizumab, abatacept, or rituximab in ordinary clinical practice. The researchers did find an apparent association between abatacept and increased risk for squamous cell skin cancer, which requires confirmation in future research.

The authors conclude, "In this study, to our knowledge one of the largest observational studies on the risk of malignant neoplasms in RA patients treated with bDMARDs to date, we found that the overall risk of developing cancer among patients with RA initiating treatment with TNFi or non-TNFi, as used in clinical practice, did not differ from that of patients with bDMARD-naive RA."

"While mostly reassuring, our findings do not preclude the existence of increased risks for site-specific cancers or risks that require longer time to become manifest," they add.

The Anti-Rheumatic Therapy in Sweden (ARTIS) Study Group used data from the Swedish Rheumatology Quality of Care Register, the nationwide Swedish Patient Register, the Swedish Cancer Register, the Prescribed Drug Register, the Total Population Register, and the Causes of Death Register for the years 2006 to 2015.

The researchers compared rates for incident malignant neoplasms in 7 cohorts: patients initiating tocilizumab (n = 1798), abatacept (n = 2021), rituximab (n = 3586), a TNFi as first-ever (n = 10,782) or second-ever (n = 4347) bDMARD, or a csDMARD (n = 46,610). They matched a general population comparator cohort (n = 107,491) in a 1:5 ratio to the bDMARD cohorts for birth year, sex, and area of residence.

Outcomes were first invasive solid or hematologic malignant neoplasm or skin cancer.

The researchers calculated hazard ratios using Cox-regression analyses adjusted for age, sex, disease characteristics, treatment characteristics, and educational level.

"In this register-based cohort study, the risk of malignant neoplasms did not differ between patients treated with a first anti-TNF drug, a second anti-TNF drug, tocilizumab, abatacept, rituximab, or conventional synthetic disease-modifying antirheumatic drugs, with the possible exception of an increased risk of squamous cell skin cancer risk in patients treated with abatacept," the authors write.

The crude incidences of new solid or hematologic malignant neoplasms per 100,000 person years were 959 for tocilizumab, 1026 for abatacept, 1074 for rituximab, 978 for TNFi as first bDMARD, 917 for TNFi as second bDMARD, and 1328 for csDMARD. The incidence in the general population was 953. Hazard ratios showed no significant differences between cancer incidences with any of the bDMARDS compared with csDMARDs.

The only exception was first invasive squamous cell skin cancer in patients with RA taking abatacept, with an incidence of 266/100,000 person years (nine events in 2014 patients) and a hazard ratio of 2.15 to 2.98. Although this might be a chance finding, the researchers note a well-established link between squamous cell skin cancer and immune incompetence.

The results of this analysis differ somewhat from earlier work by this group. The authors explain, "[T]the difference is mainly with the patients under study; the indication for starting TNFi in RA has broadened substantially over time, such that the characteristics of the patients in our current study are quite different from patients starting TNFi in 1999."

Because follow-up time was less than 10 years, the analysis provided limited information on the effect of bDMARDs on slow-developing cancers.

The authors conclude, "The overall risk of cancer among patients with RA initiating TNFi as first or second bDMARD, tocilizumab, abatacept, or rituximab does not differ substantially from that of biologic drug–naive, csDMARD-treated patients with RA, although altered risks for specific cancer types, or those with longer latency, cannot be excluded."

This research was funded by the Swedish Cancer Society, the Swedish Foundation for Strategic Research, the Stockholm County Council, and the Swedish Research Council (Vetenskapsrådet). The ARTIS Study Group conducts scientific analyses using data from the Swedish Biologics Register ARTIS run by the Swedish Society for Rheumatology. For these analyses, the Swedish Society for Rheumatology has received funding from MSD, BMS, Pfizer, Abbott Laboratories, SOBI, UCB, and Roche. Dr Askling reported research funding from AbbVie, BMS, MSD, Pfizer Roche, Astra-Zeneca, Eli Lilly, and UCB. The other authors have disclosed no relevant financial relationships.

JAMA Intern Med. Published online September 18, 2017. Abstract

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