LAS VEGAS – Concerns about use of a tumor necrosis factor inhibitor in a rheumatoid arthritis patient with a history of cancer are common, but the data are largely reassuring, according to Dr. Iain McInnes.
He used as an example a case involving a 56-year-old woman who had erosive RA that was anti-citrullinated peptide antibody–positive (ACPA+). The woman failed triple therapy, responded well to etanercept, and achieved clinical remission after 9 months. The patient then developed breast cancer and her TNF inhibitor was stopped, as recommended by current American College of Rheumatology guidelines.
Dr. Iain McInnes
The patient returned a year later after undergoing "the whole gamut from the oncological armamentarium," including chemotherapy, radiation therapy, and surgery.
"So what do you do? She wants her TNF blocker back – she did very well on it," said Dr. McInnes, who is Muirhead Chair of Medicine and Director of Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Scotland.
Prescribe a conventional disease-modifying antirheumatic drug (DMARD)? Try a different mode of action?
What if the patient is a 56-year-old female with ACPA+ erosive RA who failed triple therapy and leflunomide; is doing poorly; has a history of breast cancer treated successfully 3 years ago by lumpectomy, radiation therapy and chemotherapy; and asks for a change in therapy?
According to the ACR guidelines, any biologic agent can be used in a patient with solid malignancy or nonmelanoma skin cancer that was treated more than 5 years ago, while rituximab should be considered in those treated for a solid malignancy within the last 5 years, those treated with nonmelanoma skin cancer within the last 5 years, those treated for skin melanoma, and those treated for lymphoproliferative malignancy.
The British Society of Rheumatology guidelines are "broadly similar but less restrictive on the use of rituximab, and less restrictive of the time duration from solid malignancy to decision making," Dr. McInnes said at Perspectives in Rheumatic Diseases 2013.
A number of studies looking at whether TNF inhibitors are associated with increased cancer risk have been published and, basically, "the more one looks at the data, the less concerned one becomes," he said.
In a large meta-analysis that included 74 randomized controlled studies, more than 15,400 patients treated with TNF inhibitors, and nearly 7,500 controls, investigators found no evidence to support or refute a link between TNF inhibitors treatment and short-term risk of all cancers except nonmelanoma skin cancer. The risk of nonmelanoma skin cancer, however, was nearly more than doubled in the treatment group (Pharmacoedpidemiol. Drug Saf. 2011;20:119-30).
A 2012 study demonstrated a very low risk of malignancy among patients on TNF inhibitors across several registries (Rheum. Dis. Clin. North Am. 2012;38:761-70).
Also, a study published earlier this year showed that, in nearly 40,000 patients with various types of rheumatic diseases, treatment with anti-TNF drugs was not associated with a short-term increase in the risk of cancer, compared with commonly used therapies for immune-mediated chronic inflammatory diseases (Arthritis Rheum. 2013;65:48-58).
Another large population-based cohort study published this year (BMJ 2013;346:f1939), showed that RA patients treated with TNF inhibitors are not at increased overall risk for cancer, but they do have a 50% increased relative risk of invasive melanoma. The increase in absolute melanoma risk is small, however, and "may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons."
Notably, another large study published in 2011 linked data from multiple Swedish clinical registries of RA with nationwide data on hospitalization and outpatient visits for RA, showing that cancers that occur in patients taking TNF inhibitors are not characterized by any distinction, such as a later stage at presentation or worse survival.
"This is true whether you look at overall cancer or lung, colorectal, or hematologic cancers. You can reassure your patient," Dr. McInnes said.
As for RA patients with a history of prior malignancy, findings from a 2010 analysis of data from the British Society for Rheumatology Biologics Register showed that, in 117 patients on a DMARD and 177 on an anti-TNF drug, the risk of cancer was actually greater among those on a DMARD, with a rate of incident malignancy per 1,000 person-years of 25.3 in the anti-TNF patients, compared with 38.3 in the DMARD patients (Arthritis Care Res. 2010;62:755-63).
"When you look at the numbers they are, by and large, reassuring, and this is the message you should give to patients, but make decisions on an individual-patient basis," Dr. McInnes said.