BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. METHODS: We performed a genomewide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer !10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. RESULTS: The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P ¼ 5.88 Â 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P ¼ 6.60 Â 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone
Objective To determine whether radiologically defined sarcopenia at the C3 or L3 level as measured by computed tomography or magnetic resonance imaging is prognostic of overall survival (OS) in head and neck cancers (HNCs). Methods Literature searches of PubMed, Embase, and Scopus were conducted on July 12, 2019, to include articles written in the English language with no constraints on publication date. To be included in the analysis, articles had to report the prognostic impact of skeletal muscle mass measured radiologically at the C3 or L3 vertebral level in HNC patients; hazard ratios (HRs) for OS; 95% confidence intervals (CIs); be from a clinical trial, cohort, or case–control study; and have English full‐text availability. Articles were reviewed in consensus by two reviewers, with disagreements reviewed by a third reviewer. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses and Meta‐analysis Of Observational Studies in Epidemiology Checklist guidelines were used for reporting. Study quality assessment was performed using Quality In Prognosis Studies tool. The random‐effects DerSimonian and Laird method was used for meta‐analysis. Results Ten articles, nine retrospective and one prospective, were included in this meta‐analysis (n = 2,181 patients). Significant differences were found in OS for HNC patients with sarcopenia (HR = 1.98; 95% CI: 1.64‐2.39; P < .00001). No heterogeneity was detected in either the overall or subgroup analyses. Conclusions Radiologically defined sarcopenia is a negative predictor of OS in patients with HNC. Early detection of sarcopenia in cancer patients may help guide nutritional and adjuvant support to improve treatment outcomes. Level of Evidence NA Laryngoscope, 131:333–341, 2021
An elevated pretreatment NLR is a prognostic marker for head and neck cancer. It represents a simple and easily obtained marker that could be used to stratify groups of high-risk patients who might benefit from adjuvant therapy.
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