Cancer risks in rheumatoid arthritis patients who received immunosuppressive therapies: Will immunosuppressants work?

Abstract

BackgroundExploring the cancer risks of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARDs) can help detect, evaluate, and treat malignancies at an early stage for these patients. Thus, a comprehensive analysis was conducted to determine the cancer risk of RA patients using different types of DMARDs and analyze their relationship with tumor mutational burdens (TMBs) reflecting immunogenicity.MethodsA thorough search of PubMed, EMBASE, Web of Science, and Medline was conducted up to 20 August 2022. Standardized incidence ratios (SIRs) were constructed with a random-effect model to determine risks for different types of malignancies in comparison with the general population. We also analyzed the correlation between SIRs and TMBs using linear regression (LR).ResultsFrom a total of 22 studies, data on 371,311 RA patients receiving different types of DMARDs, 36 kinds of malignancies, and four regions were available. Overall cancer risks were 1.15 (SIR 1.15; 1.09–1.22; p < 0.001) and 0.91 (SIR 0.91; 0.72–1.14; p = 0.402) in RA populations using conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs), respectively. RA patients taking csDMARDs displayed a 1.77-fold lung cancer risk (SIR 1.77; 1.50–2.09; p < 0.001), a 2.15-fold lymphoma risk (SIR 2.15; 1.78–2.59; p < 0.001), and a 1.72-fold melanoma risk (SIR 1.72; 1.26–2.36; p = 0.001). Correlation coefficients between TMBs and SIRs were 0.22 and 0.29 from those taking csDMARDs and bDMARDs, respectively.ConclusionWe demonstrated a cancer risk spectrum of RA populations using DMARDs. Additionally, TMBs were not associated with elevated cancer risks in RA patients following immunosuppressive therapy, which confirmed that iatrogenic immunosuppression might not increase cancer risks in patients with RA.InterpretationChanges were similar in cancer risk after different immunosuppressive treatments, and there was a lack of correlation between SIRs and TMBs. These suggest that we should look for causes of increased risks from the RA disease itself, rather than using different types of DMARDs.

Cancer Risk in Patients Treated with the JAK Inhibitor Tofacitinib: Systematic Review and Meta-Analysis

“…Moreover, patients in the ORAL Surveillance study [ 19 ] were all over 50 years and had at least one major cardiovascular risk factor (e.g., smoking) that increases their neoplastic risk. In the rheumatoid arthritis population, malignancy is a leading cause of death [ 40 , 41 ], especially in patients not undergoing immunosuppressive therapy [ 42 ]. Nonetheless, this is also supported by our finding on RA indications, which is the only subgroup confirming the slightly increased risk of cancer in patients undergoing tofacitinib vs. anti-TNF.…”

Construction of shared gene signature between rheumatoid arthritis and lung adenocarcinoma helps to predict the prognosis and tumor microenvironment of the LUAD patients

“…Recent epidemiological surveys showed that the standardized incidence ratios of RA to develop cancer is 3.99 (95% CI = 3.40–4.65) ( Zhou et al, 2022 ), with cancer types ranging from different hematological malignancies which rank the first, to other various solid tumors, such as lung cancer, melanoma, cervical cancer etc. ( Zhang et al, 2022 ). Of note, lung adenocarcinoma (LUAD) was shown to be the most common lung cancers in AIDs ( Jacob et al, 2020 ) and pulmonary involvement is a common extraarticular manifestation of RA ( Sparks, 2019 ).…”

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors—A 2023 Update

“…Compared to young-onset RA (YORA), EORA patients are more likely to be male and seronegative for rheumatoid factor (RF) and anti-cyclic citrullinated protein (CCP) antibodies, and have markedly elevated C-reactive protein (CRP) levels and erythrocyte sedimentation rates, suggesting that EORA and YORA have a different pathophysiology [ 4 , 5 , 6 ]. In addition, patients with RA are at higher risk of developing malignancies, such as lymphomas, melanomas, and lung cancers, than healthy individuals [ 7 , 8 ]. Elderly patients with RA in particular are at high risk and often have a past or concurrent medical history of malignancy [ 9 ].…”