Biologic Initiation not Associated with Increased Risk of Malignancy in RA

The risk of malignancy in patients with rheumatoid arthritis (RA) is largely comparable with the general population. Further, when comparing the risk of malignancy between patients with RA initiating biologic disease-modifying antirheumatic drugs (bDMARDs) and those continuing conventional synthetic DMARDs (csDMARDs), the risk of overall, solid, and hematological malignancies was similar among both cohorts, according to a study published in RMD Open.¹

“Many questions remain, among them the potential differential risk of lymphoma with tumor necrosis factor (TNF) inhibitors according to their molecular structure,” investigators explained. “Additionally, uncertainties remain regarding the risk of some specific cancers, particularly invasive melanoma, and virus-related cancer such as cancer of the cervix that can be triggered by immunosuppressants. Regarding other bDMARDs, studies are scarce and most of them are underpowered.”

Investigators used the French national healthcare database, ‘système national des données de santé’ (SNDS), to conduct a 9-year historical Propensity Score (PS) matched cohort study between January 2006 and December 2015, which included adult patients with RA without malignancy. The database collected information on approximately 57 million citizens. Exposures, categorized by therapeutic class, began with initiation of csDMARDs and/or bDMARDs. Incident users of bDMARDs were matched on a dynamic PS and compared with patients continuing csDMARDs. The primary outcome was any incident malignancy and secondary outcomes were solid cancers and other hematological malignancies. Malignancy risks were evaluated using a Cox model.

A total of 83,076 patients with RA initiated treatment within the study period (63,837 on continued csDMARDs and 19,869 receving a bDMARD during follow-up). After PS matching, 19,727 patients receiving bDMARDs were compared with 19,727 patients remaining on csDMARDs treatment.

Malignancy was reported in 332 patients in the csDMARDs cohort and 435 in the bDMARDs group. Overall risk of malignancies was similar between both groups (HR 0.99 [95% CI 0.86 to 1.14]). Additionally, comparisons between solid cancer (HR 0.95 [95% CI 0.82 to 1.11]) and lymphoma (HR 1.35 [95% CI 0.72 to 2.53]) yielded similar results.

Results did not change when patients received bDMARDs as either monotherapy or in combination with csDMARDs. Additionally, analyses that evaluated patients starting TNF inhibitors as the first bDMARD and compared them with matched patients with RA receiving csDMARDs reported similar results for overall malignancy (HR 1.03 [95% CI 0.88 to 1.21]).

The observational nature of the study may have introduced a risk of bias, particularly because it delt with complex situations with time-dependent confounding factors. However, a cohort of patients receiving csDMARDs helped to minimize the potential impact of previous therapeutic lines in addition to implementing a time-dependent PS. While these precautionary measures ultimately reduced the study population, the results were less biased and more robust. The study was strengthened by the “high representativeness” of the SDNS, which accounted for 87% of the French population. While there is a chance that some RA diagnoses were misclassified, previous studies aligned with the prevalence of RA in this population and only included patients receiving DMARDs. Investigators also included information such as disease duration, previous DMARDs, previous RA-related hospitalizations, and both corticosteroid current and cumulative doses to determine disease severity and activity in the PS.

“Our study provided an important reassuring message for patients with RA and physicians treating them regarding the risk of malignancies associated with the use of bDMARDs,” investigators concluded. “Even in a national healthcare database, some malignancies, such as lymphoma, remained rare events that deserve to be analysed in future studies including more recently treated patients.”

Reference:

Seror R, Lafourcade A, De Rycke Y, et al. Risk of malignancy in rheumatoid arthritis patients initiating biologics: an historical propensity score matched cohort study within the French nationwide healthcare database. RMD Open. 2022;8(2):e002139. doi:10.1136/rmdopen-2021-002139