GLASGOW – Biologic treatment for rheumatoid arthritis does not increase the overall risk of solid cancers beyond that of more traditional, nonbiologic drugs, according to long-awaited data from the British Society for Rheumatology Biologics Register.
At a median follow-up of almost 5 years, the adjusted hazard ratio for all solid cancers was 0.88 (95% confidence interval, 0.65-1.17) in a comparison between anti–tumor necrosis factor (anti-TNF)-alpha therapy and nonbiologic disease-modifying antirheumatic drugs (nbDMARDs, n = 3,543) in patients without a prior history of cancer.
There was no significant difference in cancer risk between the anti-TNF drugs included in the analysis, namely etanercept (adjusted hazard ratio, 0.94; 95% CI, 0.68-1.29), infliximab (aHR, 0.87; 95% CI, 0.61-1.25), and adalimumab (aHR, 0.81; 95% CI, 0.57-1.14) versus nbDMARDs. Neither duration of follow-up nor the overall site where tumors occurred had any effect on the occurrence of solid cancers.
These data lend further support to the general safety of TNF inhibitors, and add to findings reported from the British Society for Rheumatology Biologics Register (BSRBR) and other European registries, such as the Danish Biologics Registry (DANBIO), with regard to malignancy (Rheumatology News, June 2011, p. 22).
"We do still need further follow-up to address site-specific [cancer] risk and to allow for longer latency," said Dr. Louise Mercer, May 3, at the British Society for Rheumatology annual conference (Rheumatology 2012;51:iii40, abstract O37).
Dr. Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester (England), noted that that cancer risk is already higher in patients with RA than in the general population (Rheumatology News, April 2011, p. 31). However, these latest findings from the BSRBR highlight that the use of biologic therapy doesn’t appear to add to this risk over that seen with nbDMARDs.
Data on 11,719 patients without a history of cancer who were enrolled in the BSRBR between 2001 and 2009 were used for the current analysis. Data after 2009 were not considered in order to allow for the lag time in cancer reporting from the U.K.’s National Cancer Registry into the Biologics Register. A group of 3,543 patients treated with nbDMARDs was used as the reference population.
Data adjustment took account of patients’ age at baseline, gender, duration of disease, use of nonsteroidal anti-inflammatory drugs, comorbidities, and age at time of enrollment in the U.K.-based register.
A total of 295 cancers were reported in patients treated with anti-TNF agents during a mean follow up of 4.6 years, giving a crude cancer rate of 63 per 10,000 patient-years. A total of 91 cancers were reported in patients treated with nbDMARDs over a median follow-up of 3.4 years, representing a crude cancer rate of 84 per 10,000 patient years.
With regard to the site of cancer, anti-TNFs appeared to be associated with a lower risk of lung cancer (aHR, 0.89; 95% CI, 0.46-1.74) and breast cancer (aHR, 0.99; 95% CI, 0.51-1.92) than were nbDMARDs. There was an increase in the risk of colorectal cancer (HR, 1.21; 95% CI, 0.54-2.70), but "the confidence intervals have become wider," Dr. Mercer observed.
Data on patients with a prior history of cancer have already been published by the team (Arthritis Care Res. 2010;62:755-63), but new data on patients with cervical carcinoma in situ (CIS) were reported during a poster presentation at the meeting (Rheumatology 2012;51:iii77, abstract 70).
Considering data collated through March 2011, 238 women had a prior history of cervical CIS – 48 of 2,654 (1.8%) women treated with nbDMARDs and 190 of 9,084 (2.1%) treated with anti-TNFs. Two women subsequently developed genitourinary cancer – both were treated with nbDMARDs. The rate of incident cancer was 13 per 1,000 person-years (95% CI, 2-45).
Dr. Mercer and her associates noted that there was a low level of reporting cervical CIS, which could reflect rheumatologists not being aware of abnormal cervical changes or choosing not to report in situ cancers or these prior cancers at baseline.
They concluded that "there were no new or recurrent female genital cancers among women with preexisting cervical CIS selected for treatment with anti-TNF," which should prove reassuring to women who may have a history of cervical abnormalities and who are considering anti-TNF therapy.
The BSRBR is funded by a grant from the British Society for Rheumatology. The BSR receives funding from Abbott Laboratories, Swedish Orphan Biovitrum (SOBI), Merck, Pfizer, Roche Products, and UCB Pharma. This income finances a separate contract between the BSR and the University of Manchester, which provides and runs the BSRBR. All decisions concerning data analysis, interpretation, and publications are made autonomously of any industrial contribution. Dr. Mercer reported having no personal conflicts of interest.