MTHFR C677T polymorphism may be a good predictor for MTX toxicity in adult hematological malignancies.

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Numerous studies have shown that MDR1 polymorphisms in the form of single nucleotide poymorphisms or haplptype affect ciclosporin pharmacokinetics or blood concentrations in organ transplantation patients, but some results conflict with others. WHAT THIS STUDY ADDS • We had thought that the diease condition might conceal the minor effect of MDR1 polymorphisms. • We chose myasthenia gravis patients as a population in which disease conditions were less severe. • We also used different pharmacokinetics indices, such as dose‐adjusted trough blood concentrations, dose‐adjusted peak blood concentrations and trough blood concentrations under the same ciclosporin regimen. AIMS Ciclosporin (CsA), which is widely used in autoimmune disease and transplantation, has a narrow therapeutic index. It also shows considerable interindividual variability in its pharmacokinetics, which may be attributable to polymorphisms of the multidrug efflux pump P‐glycoprotein, encoded by MDR‐1. The aim was to determine the role of genetic polymorphisms in MDR‐1 with respect to interindividual variability of CsA blood concentrations in myasthenia gravis (MG) patients. METHODS MG patients (n = 129) receiving CsA were genotyped for MDR‐1 1236C→T (exon 12), 2677G→T (exon 21) and 3435C→T (exon 26). Trough blood and peak blood concentrations were determined to see if there was correlation with the corresponding genotype. RESULTS We observed a trend for CsA blood concentrations, especially peak blood concentrations, to be higher with the wild‐type allele compared with minor alleles in genotype and haplotype. Furthermore, under the same CsA regimen, it was found that the trough concentrations of variant genotype (ABCB1 1236TT or ABCB1 2677TT) were significant greater than those of wild‐type (ABCB1 1236CC or ABCB1 2677GG, respectively) (P = 0.0222 and 0.0081). The trough concentrations of wild‐type haplotype pair group were significantly lower those that of the mutant type pair group (TT‐TT‐TT) (P = 0.007). CONCLUSIONS ABCB1 polymorphisms in both genotype and haplotype may have a minor effect on the CsA blood concentrations.

Background: Recent clinical guidelines suggest direct oral anticoagulants (DOACs) as treatment for cancer-associated thrombosis (CAT), but the strength of such recommendations was not clear. Newly released trials add uncertainties to the benefit and risk assessment between DOACs and conventional therapy (low-molecular-weight heparin [LMWH] or vitamin K antagonists [VKAs]). Objective: To evaluate the efficacy and safety of DOACs in patients with CAT, as compared with LMWH and VKAs. Methods: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) that reported outcomes of DOACs for treating CAT were included. Relative risk (RR), risk difference, and 95% CIs were pooled using the Mantel-Haenszel method. Results: A total of 8 RCTs were included. DOACs significantly reduced VTE recurrence (RR = 0.59; 95% CI = 0.48-0.73) compared with conventional therapy. Results were similar in the LMWH and VKA subgroups. DOACs had a higher, though nonsignificant, risk of major bleeding compared with LMWH (RR = 1.33; 95% CI = 0.94-1.89) but lower risk of major bleeding compared with VKAs (RR = 0.60; 95% CI = 0.39-0.93). Findings were consistent across patients with active cancer and history of cancer. Conclusion and Relevance: DOACs have better efficacy to prevent recurrent VTE compared with conventional therapy. Regarding the safety profile, DOACs may carry higher risk of bleeding compared with LMWH but lower risk of bleeding compared with VKAs. Further studies are needed to inform the optimal anticoagulation approach for different types of cancers.

Aims Renal anaemia is a common complication of chronic kidney disease (CKD). Roxadustat is the first‐in‐class oral hypoxia‐inducible factor prolyl hydroxylase inhibitor for the treatment of anaemia. In this systematic review, we aimed to investigate the efficacy and safety of roxadustat in the treatment of anaemia in CKD patients. Methods PubMed, Cochrane Library, Embase, and http://ClinicalTrials.gov databases were searched from their inception to February 2021 for randomised controlled trials (RCTs) that compared the efficacy and safety of roxadustat to those of an erythropoiesis‐stimulating agent (ESA) or a placebo in treating anaemia in CKD patients. Results Nine RCTs involving 2743 patients were found. The meta‐analysis showed that roxadustat increased haemoglobin (Hb) level by 0.91 g/dL (95% confidence interval [CI]: 0.47–1.34, P < .05), transferrin level by 0.50 mg/dL (95% CI: 0.34–0.65, P < .05), and total iron‐binding capacity by 50.64 μg/dL (95% CI: 36.21–65.07, P < .05) in CKD patients. Decreases in hepcidin (mean difference [MD] = −23.16, 95% CI: −37.12 to −9.19, P < .05) and ferritin (MD = ‐38.35, 95% CI: −67.41 to −9.29, P < .05) levels were also observed. There was no significant difference in the incidence of adverse events (AEs) (OR: 1.12, 95% CI: 0.95–1.32, P = .17) between the roxadustat and control groups; however, the incidence of serious AEs in the roxadustat group was significantly higher than that in the ESA group (OR: 1.33, 95% CI: 1.06–1.68, P < .05). Conclusion Roxadustat can significantly improve renal anaemia in CKD patients by increasing Hb level and iron metabolism. However, attention must be paid to the risk of SAEs during treatment.