In RA, Little Risk for Recurrent Cancer With Biologic Treatment

Patients with rheumatoid arthritis (RA) who had a history of cancer did not have an increased risk of new or recurrent cancers if treated with biologic therapies, a meta-analysis found.

Among patients with any previous cancer diagnosis receiving treatment with a tumor necrosis factor (TNF) inhibitor, rituximab (Rituxan), tocilizumab (Actemra), or abatacept (Orencia), the rate ratio for a new malignancy was 1.09 (95% CI 0.92-1.29, P=0.31) compared with similar patients who had not received biologic therapies, reported Paulina Szafors, MD, of the University of Montpellier-Nimes in France, and colleagues.

And among the nine cohort studies included in that analysis, representing a total of 1,930 patients given biologics and 5,630 without biologic treatment, there was little heterogeneity (I²=8%, P=0.37), the researchers reported in Arthritis Care & Research.

Patients with RA are at increased risk of malignancy, particularly lymphomas and lung cancer. Because biologic therapies alter the activities of the immune system, there have been concerns that these agents might increase the risk for cancer. Although safety reviews for these agents have not detected an increased cancer incidence among RA patients with no past history of cancer, most of the randomized studies excluded patients with previous cancer, so little is known about risks for recurrences or new cancers for these patients.

Accordingly, Szafors and colleagues conducted a systematic review and meta-analysis of studies published through 2020, initially including patients with RA, psoriatic arthritis, and ankylosing spondylitis and also targeting synthetic agents such as JAK inhibitors. There were insufficient data for the non-RA inflammatory conditions or for targeted synthetic drugs, however, so the analysis focused on RA and biologics.

The meta-analysis included 12 observational retrospective cohorts of RA patients. The majority had been treated with TNF inhibitors, with small numbers having received abatacept, rituximab, tocilizumab, or other biologics.

Follow-up averaged 3.9 to 6.8 years, and time from remission of the initial cancer until initiation of biologic therapy ranged from 6 months to 7.9 years.

Along with the analysis of biologics as a whole and all types of cancer, the researchers also considered the individual types of biologics and malignancies.

Eight studies focused specifically on patients who had received TNF inhibitors, including 1,494 patients exposed to these therapies and 4,454 with no exposure. With 164 new tumors in TNF inhibitor-treated patients and 414 in patients not on biologics, the risk of cancer recurrence was not significantly elevated (RR 1.11, 95% CI 0.85-1.46, I ²=48%, P=0.41).

Three studies presented data on the risk of new cancers in RA patients given rituximab. With 11 recurrent cancers among 124 patients receiving rituximab and 59 among the 281 not given a biologic, there was no significant increase in cancer risk (RR 0.79, 95% CI 0.41-1.53, I ²=0%, P=0.65), Szafors and co-authors reported.

Two studies examined recurrence risks for patients with a history of breast cancer. With 44 new or recurrent cancers among 496 patients who had received TNF inhibitors and 145 new cancers among 2,002 unexposed patients, there was no significantly increased risk (RR 1.21, 95% CI 0.84-1.72, I ²=0%, P=0.70).

Three studies considered cervical cancer. With neoplasia having developed in three of 1,108 patients with a history of cervical cancer or cervical intra-epithelial neoplasia given TNF inhibitors and in six of 2,526 controls, again there was no significant increased risk for new cancer (RR 0.42, 95% CI 0.01-17.29, I ²=79%, P=0.03), the investigators noted.

Four studies examined risks of new cancers among patients with skin cancer. When both non-melanoma skin cancer and melanoma were included, the risk was increased for patients on biologics (RR 1.32, 95% CI 1.02-1.72, I ²=0%, P=0.04).

However, for non-melanoma skin cancers only, there was no increased risk with biologic exposure (RR 1.28, 95% CI 0.96-1.67, I ²=0%, P=0.77) or for TNF inhibitor use specifically (RR 1.27, 95% CI 0.96-1.68, I ²=0%, P=0.09).

Szafors and co-authors noted that only one study focused on recurrent melanomas, the case numbers were small, and only in situ forms were reported — cautioning, therefore, that the “results do not allow for conclusions because of the small number of retrieved studies, and further studies are needed.”

Limitations to the analysis, the researchers said, included that most of the studies evaluated did not report stage classification of the malignancies or RA disease activity, and only one provided data on tobacco use, an established risk factor for many types of cancer.