Patients with rheumatoid arthritis (RA) with a history of solid cancer were at no greater risk for cancer recurrence after tumor necrosis factor inhibitor (TNFi) treatment than similar patients not treated with TNFi, according to data from Swedish RA and cancer registries. However, the researchers caution that they are unable to rule out some risk completely
Pauline Raaschou, MD, Ph.D., and colleagues from the ARTIS Study Group reported the results of the nationwide population-based cohort study in an article published online August 14 in the Annals of Internal Medicine.
"Our findings suggest that TNFi treatment was not associated with an increased risk for cancer recurrence in patients with RA and a history of cancer compared with those who had a similar cancer history and were selected to receive other RA treatments. However, as suggested by the upper limit of the CI [confidence interval] for several risk estimates, a clinically meaningful risk cannot be completely ruled out."
Solomon said, "From the clinician's standpoint, it would be reasonable to conclude that TNFi treatment is not associated with increased risk for cancer recurrence in RA patients, based on this recent paper plus prior work. Clinicians and patients should not avoid these agents based on a prior history of cancer."
The ARTIS researchers used data from Swedish cancer and RA registries to investigate whether TNFi treatment in patients with RA is associated with increased risk for cancer recurrence.
They included patients with RA who began TNFi treatment between 2001 and 2015 and had previously been diagnosed with solid cancer. They matched these subjects with patients with RA with the same cancers who had not received any type of biologic.
The report included three matched groups of patients with RA and one unmatched group
Group A compared cancer recurrence rates for 467 patients with RA who began TNFi from 2001 to 2015 vs. recurrence in an individual matched cohort of 2164 patients with RA and similar cancers but no exposure to TNFi. With a mean follow-up of 5.3 years in the TNFi group and 4.3 in the unexposed group, the adjusted hazard ratio (HR) for first cancer recurrence was 1.06.
Group B compared cancer recurrence rates for 223 patients with cancer diagnosed in 2001 or later who started TNFi in 2001 or later vs. 1070 similar biologic-naive patients with RA. The adjusted HR for first cancer recurrence was 1.08 (95% CI, 0.65 – 1.80; 10% vs 7.3%).
Group C compared cancer recurrence rates for 138 TNFi-treated vs. 649 biologic-naive patients with RA, all with index cancers diagnosed from 2003 to 2015. The adjusted HR was 1.15 (95% CI, 0.53 – 2.47; 12% vs 6%).
The unmatched analysis included 3826 patients with RA with solid cancers diagnosed between 2001 and 2015 and no history of exposure to biologics. Of these, 178 patients began taking TNFi after they were included in the study, and their outcomes were compared with those who had not begun TNFi treatment.
Adjusted HR was 1.24 (95% CI, 0.74 – 2.07; 5% vs. 9%, respectively), and there were no associations of cancer recurrence either with time before starting TNFi or with time since cancer diagnosis.
A study limitation is that the patients who were prescribed TNFi during the time most clinical guidelines advised against that treatment might have had lower cancer recurrence risk because of other factors, such as more favorable tumor characteristics. They also had higher use of conventional DMARDs and prednisolone and a lower prevalence of heart failure, which the authors describe as "unexpected."
The authors caution that their results might not be directly applicable to patients with ongoing cancer or recent cancer diagnosis, or to all cancer types, as the study included only solid cancers.
Solomon added, "The risk estimates have a 95% [CI] that includes a small increased risk. Thus, it is prudent to recognize the possibility that there may be a small increased risk."