Abstract
Objective: Concerns exist regarding the potential development of malignancy and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. We assessed the extent to which biologic therapy may increase the risk of malignancy and tuberculosis in patients with SpA by meta-analysis to derive estimates of sparse harmful events occurring in Randomized Controlled Trials (RCTs). Methods: A systematic literature search was conducted in PubMed, EMbase, Web of Science, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating the risk of sparse harmful events of biologic therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto OR for malignancy and tuberculosis in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using Cochrane Risk of Bias tool. Results: In total, 63 studies were included in this meta-analysis, and 83 patients and 7 patients developed malignancy and tuberculosis, respectively. Overall, the risk of malignancy and tuberculosis was increased in SpA patients treated with biologics compared to placebo (malignancy: Peto OR: 2.49, 95%CI: 1.61–3.87, p < 0.001; tuberculosis: Peto OR: 5.98, 95%CI: 1.29–27.76, p = 0.022). Remarkably, compared to placebo, there was higher risk of malignancy for IL-17 inhibitors (Peto OR: 3.68, 95%CI: 1.20–11.30, p = 0.023) and small molecule targeted drugs (Peto OR: 3.08, 95%CI: 1.37–6.90, p = 0.043) in peripheral SpA, and for TNF receptor-Fc fusion protein in axial SpA (Peto OR: 7.18, 95%CI: 1.21–42.69, p = 0.030). Besides, the risk of tuberculosis was higher for anti-TNFα antibody in axial SpA (Peto OR: 6.17, 95%CI: 1.03–37.13, p = 0.046). Conclusion: This meta-analysis showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and small molecule targeted drugs, a slightly increased risk of malignancy in TNF receptor-Fc fusion protein in axial SpA, and increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. These findings need to be validated by studies with larger population and longer follow-up.
Highlights
Spondyloarthritis (SpA) is a series of chronic inflammatory conditions that have a range of manifestations, including predominantly axial SpA (radiographic axial SpA and non-radiographic axial SpA) and peripheral SpA
Concerns have been raised about the safety of biologics or small molecular targeted drugs, especially with regard to malignancies and tuberculosis, because they can interfere with the immune system
Our work shows that there is an elevated risk of malignancies and tuberculosis in patients with SpA receiving biologics or small molecular targeted drugs therapy, compared to placebo
Summary
Spondyloarthritis (SpA) is a series of chronic inflammatory conditions that have a range of manifestations, including predominantly axial SpA (radiographic axial SpA (axSpA) and non-radiographic axial SpA (non-axSpA)) and peripheral SpA (enteropathic arthritis, reactive arthritis, and psoriatic arthritis). People with predominantly axSpA may have additional peripheral symptoms, and vice versa. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), or a combination of both, can usually ameliorate disease activity and retard joint damage, thereby improving quality of life of patients with SpA. In a sizeable proportion of patients with SpA, NSAIDs or csDMARDs fail or are not tolerated. For these patients not responding to NSAIDs or csDMARDs, biologics or small molecular targeted drugs can provide clinically important improvement via targeting specific inflammatory mediators in inflammatory pathways, alleviating inflammation, and better controlling symptoms and structural destruction. Concerns have been raised about the safety of biologics or small molecular targeted drugs, especially with regard to malignancies and tuberculosis, because they can interfere with the immune system
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