Comparative efficacy and safety of combination therapy with infliximab for Crohn's disease: a systematic review and network meta-analysis.

PURPOSE: There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of combination therapy and infliximab (IFX) monotherapy in CD patients. METHODS: We identified randomized controlled trials (RCTs) in CD patients who were given IFX-containing combination therapy versus IFX monotherapy. Induction and maintenance of clinical remission were the efficacy outcomes, while adverse events were the safety outcomes. The surface under cumulative ranking (SUCRA) probabilities was used to assess ranking in the network meta-analysis. RESULTS: In total, 15 RCTs with 1586 CD patients were included in this study. There was no statistical difference between different combination therapies in induction and maintenance of remission. In terms of inducing clinical remission, IFX + EN (SUCRA: 0.91) ranked highest; in terms of maintaining clinical remission, IFX + AZA (SUCRA: 0.85) ranked highest. There was no treatment that was significantly safer than the others. In terms of any adverse events, serious adverse events, serious infections, and infusion/injection-site reactions, IFX + AZA (SUCRA: 0.36, 0.12, 0.19, and 0.24) was ranked lowest for all risks; while IFX + MTX (SUCRA: 0.34, 0.06, 0.13, 0.08, 0.34, and 0.08) was rated lowest for risk of abdominal pain, arthralgia, headache, nausea, pyrexia, and upper respiratory tract infection. CONCLUSION: Indirect comparisons suggested that efficacy and safety of different combination treatments are comparable in CD patients. For maintenance therapies, IFX + AZA was ranked highest for clinical remission and lowest for adverse events. Further head-to-head trials are required.

Construction of a novel signature and prediction of the immune landscape in gastric cancer based on necroptosis-related genes.

Necroptosis, a type of programmed cell death, has become a potential therapeutic target for solid tumors. Nevertheless, the potential roles of necroptosis-related genes (NRGs) in gastric cancer (GC) remain unknown. The objective of the present study was to create a necroptosis-related prognostic signature that can provide more accurate assessment of prognosis in GC. Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data, we identified differentially expressed NRGs. Univariate analysis and Lasso regression were performed to determine the prognostic signature. Risk scores were calculated and all GC patients were divided into high- and low-risk score group according to the median risk score value. The robustness of this signature was externally validated with data from GSE84437 cohort (n = 431). Survival analysis revealed high-risk score patients had a worse prognosis. Results evidenced that the signature was an independent prognosis factor for survival. Single-sample sequence set enrichment analysis (ssGSEA) exhibited different enrichment of immune cells and immune-related pathways in the two risk groups. Furthermore, a predictive nomogram was generated and showed excellent predictive performance based on discrimination and calibration. In addition, the risk score positively correlated with tumor mutational burden and was associated with sensitivity to multiple anti-cancer drugs. Overall, our work demonstrates a close relationship between necroptosis and the prognosis of GC. The signature we constructed with potential clinical application value, can be used for prognosis prediction and being a potential therapeutic responses indicator in GC patients.