SNOWMASS, COLO. – The use of anti–tumor necrosis factor biologics in patients with rheumatoid arthritis, psoriasis, and other serious autoimmune diseases is not associated with increased risk of most forms of cancer, with two highly visible and important exceptions: nonmelanoma skin cancer and malignant melanoma.
That’s the largely reassuring conclusion to be drawn from two large studies conducted by researchers at Stockholm’s Karolinska Institute, according to Dr. Jeffrey R. Curtis, director of the arthritis clinical intervention program at the University of Alabama, Birmingham.
Dr. Jeffrey R. Curtis
The Swedish group conducted a comprehensive meta-analysis of all 74 pharmaceutical company–sponsored randomized controlled trials of anti-TNF biologics lasting at least 4 weeks. The investigators used individual patient data for 15,418 anti-TNF recipients and 7,486 subjects randomized to methotrexate and other comparators. About half of the randomized trials focused on rheumatoid arthritis (RA) patients; the other half involved patients with the other approved indications for anti-TNF therapy.
The use of individual patient data was a nuance of the meta-analysis that wowed Dr. Curtis.
"This is a really great paper. One of the reasons I was very impressed with it is that getting drug companies to give up any raw person-level data to anybody is difficult. The European Medicines Agency requested it, and that’s probably the only reason it happened," Dr. Curtis observed at the Winter Rheumatology symposium sponsored by the American College of Rheumatology.
The overall relative risk for all forms of cancer, excluding nonmelanoma skin cancer, in patients on anti-TNF biologics was 0.99. Their cancer rate was 641 per 100,000 person-years (Pharmacoepidemiol. Drug Saf. 2011;20:119-30).
"You can tell your patients the risk for cancer is less than 1 in 100 – it’s about 6 per 1,000 – and it’s not increased compared to background therapy," the rheumatologist said.
The exception was nonmelanoma skin cancer. The relative risk for this malignancy among users of all anti-TNF biologics was increased twofold.
In a separate study, the same group used prospectively recorded data from Swedish national registries to investigate the association between anti-TNF therapy and melanoma. This analysis involved 10,878 RA patients treated with anti-TNF biologics, 42,198 others who were not, and 162,743 matched controls from the general population.
Compared with controls, RA patients not on anti-TNF biologics did not have a significantly increased risk of malignant melanoma. However, the 38 first invasive melanomas that occurred in RA patients taking a TNF antagonist signified a 1.5-fold increased risk of this malignancy compared to the general population. This 50% increase in relative risk was statistically significant. The absolute increase in risk was quite small: 20 additional cases per 100,000 person-years. The number needed to harm – that is, the number of patients who needed to be treated with an anti-TNF biologic to cause one additional case of melanoma – was 50,000 (BMJ 2013;346:f1939 [doi: 10.1136/bmj.f1939]).
Dr. Curtis noted that patients who have been urged to consider going on a TNF antagonist often return to the office waving a printout of the product labeling that warns of the possibility of malignancy.
"The bottom line: I tell patients that based on the data that there doesn’t appear to be an increased risk for all types of cancer, including hematologic, with the exceptions of nonmelanoma skin cancer and melanoma. Those are the two we need to advise patients about," he said.
Dr. Curtis reported receiving funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, and 10 pharmaceutical companies.