No Added Cancer Risk with Rheumatoid Arthritis Drugs

September 19, 2017

Treatment with a TNF inhibitor, tocilizumab, abatacept, or rituximab does not seem to result in more malignant neoplasms.

The overall risk of cancer in patients with rheumatoid arthritis who are initiating tumor necrosis factor (TNF) inhibitors as first or second biological disease-modifying antirheumatic drug (bDMARD) therapy, tocilizumab, abatacept, or rituximab does not differ substantially from that in biologic drug–naive, conventional synthetic DMARD (csDMARD)–treated patients with the disease.

However, altered risks for specific cancer types, or those with longer latency, cannot be excluded.

Considering the widespread use of biological immunomodulators to treat chronic inflammatory conditions and the concern that immunomodulation may alter cancer risk and progression, researchers at the Karolinska Institutet and Karolinska University Hospital in Stockholm conducted a national register–based prospective cohort study to assess the risk of incident malignant neoplasms in patients with rheumatoid arthritis treated with bDMARDs.

Five outcomes were assessed separately: (1) a first invasive solid or hematologic malignant neoplasm, excluding nonmelanoma skin cancer (NMSC); (2) a first invasive solid malignant neoplasm, excluding NMSC; (3) a first invasive hematologic malignant neoplasm; (4) a first invasive squamous cell skin cancer; and (5) a first invasive melanoma.

A total of 15,129 initiations of a TNF inhibitor as the first or second bDMARD were identified, along with 7405 initiations of other bDMARDs and 46,610 csDMARD users. The observed numbers of events (crude incidence per 100,000 person-years) for a first invasive solid or hematologic malignant neoplasm were 50 (959) for tocilizumab, 61 (1026) for abatacept, 141 (1074) for rituximab, 478 (978) for initiators of a TNF inhibitor as first bDMARD, and 169 (917) for a TNF inhibitor as second bDMARD.

There were no statistically significant differences between initiators of a first or second TNF inhibitor, or other bDMARDs, and bDMARD-naive rheumatoid arthritis for any of 25 drug- and outcome-specific comparisons, except for abatacept and an increased risk of squamous cell skin cancer.

Based on 17 events of squamous cell skin cancer in the abatacept cohort, an increased risk vs csDMARD was observed.

There was no increased risk of malignant neoplasms overall and no increase in risk among patients starting a TNF inhibitor as second bDMARD.

The authors concluded that treatment with a TNF inhibitor as first or second bDMARD, tocilizumab, abatacept, or rituximab does not seem to increase the total occurrence of malignant neoplasms. But they cautioned, “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.”

The researchers published their findings online September 18, 2017 on JAMA Internal Medicine.

References:

Wadstrom H, Frisell T, Askling J, for the Anti-Rheumatic Therapy in Sweden (ARTIS) Study Group. “Malignant Neoplasms in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors, Tocilizumab, Abatacept, or Rituximab in Clinical Practice: A Nationwide Cohort Study From Sweden.” JAMA Intern Med. Published online September 18, 2017. doi:10.1001/jamainternmed.2017.4332