TNFi Unlikely to Raise Cancer Recurrence Risk in RA

Janis C. Kelly

August 14, 2018

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 completely rule out some risk.

Pauline Raaschou, MD, PhD, 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.

"[O]ur 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."

Daniel Solomon, MD, MPH, told Medscape Medical News that the results of the ARTIS analysis are in line with prior work and that their methods are very strong. Solomon, who was not involved in the study, is chief of the Section of Clinical Sciences, Division of Rheumatology and Division of Pharmacoepidemiology at Brigham and Women's Hospital, and Matthew H. Liang Distinguished Professor of Medicine at Harvard Medical School, both in Boston.

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 a 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 3 matched groups of patients with RA and one unmatched group.

Group A compared cancer recurrence rates for 467 patients with RA who began TNFi during 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 (95% confidence interval [CI], 0.73 - 1.54; 9.0% vs 7.2%).

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."

The study was supported by ALF (agreement concerning medical education and research in health and medical care in Stockholm County Council), the Swedish Cancer Society, the Swedish Foundation for Strategic Research, and the Swedish Research Council. One coauthor reports grants and personal fees from Bristol-Myers Squibb, Roche, and AbbVie and personal fees from Pfizer and Novartis outside the submitted work. Another coauthor reports grants from AbbVie, Bristol-Myers Squibb, Lilly, Merck, Pfizer, Roche, Samsung Bioepis, and UCB. The other coauthors and Solomon have disclosed no relevant financial relationships.

Ann Intern Med. Published online August 13, 2018. Abstract

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