LIVERPOOL, ENGLAND – The risk of recurrent cancer in patients with rheumatoid arthritis did not increase with the use of biologic therapies, according to data just released from the British Society for Rheumatology Biologics Registers’ Rheumatoid Arthritis Register.
In fact, the risk of repeated cancer in patients with prior malignancies treated with biologic therapies was apparently decreased by around 50%, when compared with treatment with nonbiologic disease-modifying antirheumatic drugs (nbDMARDs).
The hazard ratios, adjusted for age and sex, for recurrent cancer were 0.55 for patients treated with drugs directed at tumor necrosis factor (TNF)-alpha and 0.47 for patients treated, off-label, with rituximab vs. nbDMARDs.
However, Dr. Luca Silva-Fernandez, who presented the findings at the British Society for Rheumatology annual conference, noted that patients treated with nbDMARDs were perhaps at higher risk of recurrent disease than were those who were treated with biologic agents at the start of their treatment, so the data do not imply that biologic agents are less likely to cause recurrent disease than do the older RA therapies.
"Our data suggest that patients with RA and prior malignancy selected to receive either an anti-TNF or rituximab therapy in the U.K. do not seem to have an increased risk of future incident malignancy," said Dr. Silva-Fernandez.
Patients treated with anti-TNFs or rituximab were more likely to have incident cancers, added Dr. Silva-Fernandez of the Arthritis Research UK Epidemiology Unit at the University of Manchester, England, where the BSRBR-RA Register is run.
Previous data on the use of biologic therapies in patients with prior cancer were published from the British Society for Rheumatology Biologics Registers (BSRBR) 4 years ago (Arthritis Care Res. 2010;62:755-63). These considered 293 patients with a prior malignancy identified from over 14,000 patients with RA enrolled in the register at the time. The present analysis included 425 patients who had cancer before being enrolled in the BSRBR-RA Register, which at the time of the updated analysis included around 19,000 patients.
In total, 425 new malignancies were detected in 159 of 3,787 (1.7%) patients who had been treated with an nbDMARD, 243 of 14,168 (8.9%) patients treated with an anti-TNF drug, and 23 of 257 (4.2%) patients who had received rituximab for the treatment of their RA.
There were several differences in baseline characteristics among the three groups. The mean age of patients in each treatment arm was 66.1, 62.7, and 67.3 years, respectively. A higher percentage (81%) of anti-TNF-treated patients were female when compared with the nbDMARD (74%) and rituximab (65%) arms. Biologic-treated patients tended to have a longer mean RA disease duration (anti-TNF 12 years and rituximab 14 years) than did the nbDMARD-treated patients (8 years), and higher disease severity scores at enrollment into the BSRBR-RA Register. The median time between the previous and current malignancy was 7.9 years for nbDMARDs, 11.5 years for anti-TNFs, and 5.4 years for rituximab.
The crude incident malignancy rates were 47/1,000 person-years in the nbDMARD cohort, 24/1,000 person-years in the anti-TNF-treated patients, and 25/1,000 person-years in the group treated with rituximab. Dr. Silva-Fernandez reported that the median follow-up was much shorter in rituximab-treated patients, at 3.9 years, than both the nbDMARD- (6.6 years) and anti-TNF–treated (6.9 years) groups.
After her presentation, Dr. Silva-Fernandez was asked to comment on the apparent "protective" effect of anti-TNFs on the recurrence of cancer. She replied that the nbDMARD and biologic groups were not really comparable, referring back to the differences in baseline characteristics, so such an association cannot be claimed.
With regards to a question on the use of rituximab in RA patients with a history of prior cancer, which was "off label" in this instance as it wasn’t used after anti-TNFs but "up-front," this might reflect a "channeling bias" on the part of the physicians, commented Dr. Kimmie Hyrich.
"These patients were those who had received rituximab as their first biologic for a number of reasons," said Dr. Hyrich, one of the principal investigators for the BSRBR-RA Register. "For many of them, it may have been a past cancer that made that decision," she added.
"I think, as physicians, we have a comfort in using rituximab in patients with past cancer, because it is not an absolute contraindication, so I think this is physician choice, and that’s probably why an off-license decision to treat with rituximab was made in these patients," said Dr. Hyrich, also from the University of Manchester, England.
Although patients with nonmelanoma skin cancer (NSMC) were excluded from the present analysis, Dr. Hyrich also noted in response to a question that the BSRBR RA Register team had previously reported on the rates of recurrence in patients with and without a prior history of this type of skin cancer.